GLUTAMINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
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., 1960Glutamine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84439-9 1. Glutamine-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 glutamine. 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 GLUTAMINE .............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Glutamine ..................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 60 The National Library of Medicine: PubMed ................................................................................ 79 CHAPTER 2. NUTRITION AND GLUTAMINE .................................................................................. 127 Overview.................................................................................................................................... 127 Finding Nutrition Studies on Glutamine .................................................................................. 127 Federal Resources on Nutrition ................................................................................................. 132 Additional Web Resources ......................................................................................................... 132 CHAPTER 3. ALTERNATIVE MEDICINE AND GLUTAMINE ............................................................ 135 Overview.................................................................................................................................... 135 National Center for Complementary and Alternative Medicine................................................ 135 Additional Web Resources ......................................................................................................... 163 General References ..................................................................................................................... 168 CHAPTER 4. DISSERTATIONS ON GLUTAMINE .............................................................................. 169 Overview.................................................................................................................................... 169 Dissertations on Glutamine ....................................................................................................... 169 Keeping Current ........................................................................................................................ 170 CHAPTER 5. CLINICAL TRIALS AND GLUTAMINE......................................................................... 171 Overview.................................................................................................................................... 171 Recent Trials on Glutamine ....................................................................................................... 171 Keeping Current on Clinical Trials ........................................................................................... 171 CHAPTER 6. PATENTS ON GLUTAMINE ......................................................................................... 173 Overview.................................................................................................................................... 173 Patents on Glutamine ................................................................................................................ 173 Patent Applications on Glutamine ............................................................................................ 202 Keeping Current ........................................................................................................................ 244 CHAPTER 7. BOOKS ON GLUTAMINE ............................................................................................ 245 Overview.................................................................................................................................... 245 Book Summaries: Federal Agencies............................................................................................ 245 Book Summaries: Online Booksellers......................................................................................... 246 Chapters on Glutamine .............................................................................................................. 247 CHAPTER 8. PERIODICALS AND NEWS ON GLUTAMINE............................................................... 249 Overview.................................................................................................................................... 249 News Services and Press Releases.............................................................................................. 249 Newsletter Articles .................................................................................................................... 251 Academic Periodicals covering Glutamine................................................................................. 251 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 253 Overview.................................................................................................................................... 253 U.S. Pharmacopeia..................................................................................................................... 253 Commercial Databases ............................................................................................................... 254 Researching Orphan Drugs ....................................................................................................... 254 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 259 Overview.................................................................................................................................... 259 NIH Guidelines.......................................................................................................................... 259 NIH Databases........................................................................................................................... 261 Other Commercial Databases..................................................................................................... 263 The Genome Project and Glutamine .......................................................................................... 263
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APPENDIX B. PATIENT RESOURCES ............................................................................................... 269 Overview.................................................................................................................................... 269 Patient Guideline Sources.......................................................................................................... 269 Finding Associations.................................................................................................................. 271 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 273 Overview.................................................................................................................................... 273 Preparation................................................................................................................................. 273 Finding a Local Medical Library................................................................................................ 273 Medical Libraries in the U.S. and Canada ................................................................................. 273 ONLINE GLOSSARIES................................................................................................................ 279 Online Dictionary Directories ................................................................................................... 279 GLUTAMINE DICTIONARY...................................................................................................... 281 INDEX .............................................................................................................................................. 385
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with glutamine 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 glutamine, 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 glutamine, 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 glutamine. 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 glutamine, 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 glutamine. 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 GLUTAMINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on glutamine.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and glutamine, 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 “glutamine” (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: •
Effect of Growth Hormone, Glutamine, and Diet on Adaptation in Short-Bowel Syndrome: A Randomized, Controlled Study Source: Gastroenterology. 113(4): 1074-1081. October 1997. Summary: The effects of parenteral growth hormone, glutamine supplementation, and a high carbohydrate, low fat (HCLF) diet on gut adaptation in short bowel syndrome are unclear. This article reports on a study undertaken to compare effects of this treatment regimen and placebo in patients with short bowel syndrome. The randomized, 6 week, double blind crossover study investigated eight patients with short bowel syndrome (average small bowel length, 71 cm; mean duration, 12.9 years). Active treatment was growth hormone, oral glutamine, and the HCLF diet for 21 days. The weight, basal metabolic rate, nutrient and electrolyte balance, serum insulin-like growth factor 1 levels, D-xylose absorption, morphology and DNA proliferation of small intestinal
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Glutamine
mucosa, and gastrointestinal transit were evaluated. Active treatment transiently increased body weight, significantly but modestly increased the absorption of sodium and potassium, and decreased gastric emptying. The assimilation of macronutrients, stool volumes, and morphometry of small bowel mucosa were not statistically different in the two treatment arms. 4 figures. 1 table. 43 references. (AA-M). •
Role of Glutamine in TPN Source: Nutrition and the M.D. 17(3): 1, 3. March 1991. Summary: This article briefly explores the role of glutamine in total parenteral nutrition (TPN). Glutamine is the most abundant free amino acid in plasma, intracellular pools, and skeletal muscle, and is a key energy source for the small intestinal mucosa. Under normal conditions, the gut utilizes glutamine and glucose and releases alanine and ammonia. The article reviews some current research into the role of glutamine and how it can be successfully incorporated into a TPN regimen. The article concludes that, in certain conditions, glutamine may be an essential nutrient, and in these situations, intravenous glutamine-dipeptides may be an effective way to provide glutamine.
Federally Funded Research on Glutamine The U.S. Government supports a variety of research studies relating to glutamine. 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 glutamine. 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 glutamine. The following is typical of the type of information found when searching the CRISP database for glutamine: •
Project Title: ADJUVANT NUTRITION FOR CRITICALLY III TRAUMA PATIENTS Principal Investigator & Institution: Rathmacher, John A.; Metabolic Technologies, Inc. 2625 N Loop Dr, Ste 2150 Ames, Ia 50010 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2004 Summary: (provided by applicant): Of the four million cases of trauma cases each year that will require hospitalization, 200,000 will be classified as severe trauma. During the hospital stay, malnutrition is a major complication in about 50% of the patient population. The result is muscle wasting which is a major risk factor for increased morbidity and mortality. In the study proposal presented we postulate that supplementation with Beta-hydroxy-Beta-methylbutyrate (HMB), arginine and
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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glutamine (HMB/Arg/Gln) to these severely traumatized patients can stem the loss of muscle tissue and whole body nitrogen and in turn decrease morbidity and mortality. This hypothesis is based on two recent studies showing the same nutritional mixture of HMB/Arg/Gln can reverse the muscle wasting associated with AIDS and Cancer. The hypermetabolic state seen in AIDS and cancer have a similar multilifactorial etiology seen in trauma. There is an increase in the mobilization of fat and muscle, increased or normal metabolic rate, increased protein breakdown, and an increased or normal glucose turnover. In addition, HMB alone has been shown to reduce nitrogen loss, decrease muscle proteolysis and muscle damage within the first 48 hours to three week after initiating supplementation. Male and female patients (n=100) will be recruited at the time of admittance to the Trauma ICU with an ISS of greater than 18 Patients who meet the inclusion/exclusion will be randomized to receive either 1) standard tube feed plus HMB/Arg/Gln, standard tube feed plus HMB alone, or standard tube feed (control) in a blinded fashion. Clinical outcomes measures will be assessed through out the hospital stay and on a outpatient basis on week 4 and week 12. Muscle proteolysis and nitrogen economy will be evaluated on daily basis while in the hospital and after 4 weeks on an out patient basis. If as expected, Phase I results confirm the effectiveness of the nutrient mixture in trauma patients. Expanded multicenter studies will be proposed in Phase II. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMINO ACID TRANSPORT AFTER SMALL BOWEL RESECTION Principal Investigator & Institution: Sax, Harry Charles.; Professor of Surgery; Surgery; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-MAR-2005 Summary: Short bowel syndrome is a devastating clinical condition which leads to dehydration, muscle wasting, debilitation and death. Although the residual bowel has the capacity to adapt to its reduced surface area, this process is often inadequate and may require lifetime total parenteral nutrition, a modality with serious metabolic and economic consequences. Growth factors can improve adaptation in part by increasing the enterocyte's ability to transport luminal nutrients. A major nutrient glutamine (GLN) is the primary oxidative fuel for the enterocyte. The parenteral administration of epidermal growth factor (EGF) and/or human growth hormone (GH) increases sodiumdependent glutamine transport after 70% enterectomy in rabbits. The specific timing, route of administration, mechanisms of action, and potential synergistic effects of these two compounds remain to be elucidated. EGF binding activates the EGF receptor (EGFR). In cell suspensions derived from both human jejunum and C2BBE1cell line, EGF increases glutamine transport, upregulation is blocked by tyrosine kinase inhibitors which implicates a role for EGFR signaling transduction pathways. GH independently may also act through EGFR. It is hypothesized that the combination of EGF and GH upregulate sodium-dependent glutamine transport through EGFR signal transduction pathways. The specific aims of the proposal are to 1) optimize glutamine transport mediated by EGF/GH through EGFR in rabbits after massive enterectomy; 2) determine the involvement of EGFR signal transduction pathways in altering glutamine transport by EGF/GH exposure in C2BBE1cell line; 3) to investigate the effects of EGF/GH via EGFR in upregulating glutamine transport in human small bowel. The investigators plan to use three models of small bowel function: 70% enterectomy in the rabbit, the human cell line C2BBE1 in Transwells and human small bowel as an enterocyte suspension or as a neurovascularly intact loop. It is hypothesized that a better understanding of mechanisms involved in growth factor induced upregulation of
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Glutamine
nutrient transport will have significant clinical implications in developing safe and innovative strategies to treat patients with short bowel syndrome and other malabsorptive states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METABOLISM
ANTISENSE
INHIBITION
OF
RETINAL
GLUTAMATE
Principal Investigator & Institution: Danias, Ioannis J.; Ophthalmology; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The objective of this K08 project is to test one of the two major current hypotheses about the role of glutamate in glaucomatous retinal ganglion cell (RGC) death. According to this hypothesis one result of elevated IOP is a derangement of the glutamate metabolic cycle in RGCs. This derangement results in glutamate excitotoxicity that has a primary role in the pathogenesis of glaucoma. Aim 1 and 2 of this project test the second component of this hypothesis; aim 3 tests the first component. Aim 1 is to determine the effects of a deranged glutamate metabolic cycle in the retina on the RGC function and survival. Antisense oligonucleotides to the glutamate metabolizing enzymes, glutamate dehydrogenase (GDH) and glutamine synthetase (GS) and to glutamate transporters (GLAST) will be used to inhibit glutamate metabolism and uptake in RGCs. Their effects will be determined in tissue culture and then following intra-vitreal administration rats to assess RGC survival, activities and amounts of GDH. GS and GLAST, intra-vitreal glutamate concentrations, and visual function by electroretinography. Aim 2 tests whether glutamate antagonists and anti-apoptosis agents can reverse the effects of a deranged glutamate cycle in the retina caused by the antisense oligonucleotides. Aim 3 is to determine whether changes in the glutamate metabolic cycle similar to those induced by the use of antisense oligonucleotides to GDH, GS and GLAST are present in a chronically elevated IOP model of glaucoma in rats. The K08 candidate has recently completed a clinical fellowship in the field of glaucoma and has begun a tenure track academic career in Mt. Sinai School of Medicine. While he does have some prior fundamental research experience, in order to embark upon the proposed studies he must first strengthen his skills in the areas of antisense design and pharmacokinetics and in some specific methods that will be used in testing the animals and assessing the outcomes. Mentoring will be provided by senior scientists, experts in these areas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASES OF CIRRHOSIS IN ALCOHOLIC LIVER DISEASE Principal Investigator & Institution: Zern, Mark A.; Director, Div. Gastroenterology; Internal Medicine; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 95616 Timing: Fiscal Year 2002; Project Start 01-SEP-1988; Project End 31-MAR-2006 Summary: This proposal is a continuation of our studies which attempt to elucidate the molecular bases of cirrhosis in alcoholic liver disease. Hepatic fibrogenes caused by alcohol abuse or other etiologies is a complex process that involves a balance between liver cell proliferation and cell death, as well as the increased deposition and modeling of extracellular matrix (ECM) proteins. Our recent studies provide evidence for the significance of one factor, tissue transglutaminase (tTG), in many of these interactions. This ubiquitous enzyme has characteristics that may induce either apoptosis or cell
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proliferation, and it appears to contribute to the fibrotic process in a number of ways. This proposal is an attempt to elucidate the mechanisms by which tTG affects the process of hepatic mitogenesis or apoptosis, especially as it pertains to ethanol administration. Specific Aims: 1) To determine the pathways and functional significance of alpha-1 adrenergic signaling in hepatocytes; 2) To investigate the downstream effects of alpha-1 adrenergic signaling on hepatocyte mitogenesis; and 3) To delineate the mechanisms by which tTGase cross-linking activity inhibits proliferation and enhances apoptosis in hepatocytes. These studies will entail determining whether phenylephrineinduced hepatocyte mitogenesis acts through alpha-1B adrenergic receptor binding coupled to the tTGase G-protein subunit, Galphah, whether this activates the MAPK pathway, and by what mechanism this activation may be occurring. In addition, the mechanism by which tTGase cross-linking activity may affect upstream events in the apoptosis cascade will also be explored. Health Relatedness: It is hoped that by better understanding the molecular mechanisms by which ethanol affects fibrogenesis, hepatic mitogenesis, and apoptosis, more effective and rational therapeutic intervention may be developed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOLOGY OF IL-4 RECEPTOR ALLELIC VARIANTS Principal Investigator & Institution: Khurana Hershey, Gurjit K.; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 45229 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-MAY-2005 Summary: This is the first revision of a proposal by a New Investigator to look at potential genetic abnormalities that may predispose individuals to asthma. The cytokine IL-4 has been shown to be important in the development of many asthmatic lesions. IL-4 binds to the IL-4 receptor alpha (IL-4Ra). This group previously has described a novel allele of IL-4Ra in which Arg replaces glutamine at position 576. This allele, named the R576 IL-4Ra allele, correlates with a ninefold increase in atopy risk, and is also associated with increased IL-4 responsiveness. There are now at least five additional polymorphic variants of IL-4Ra, and the purpose of this application is to determine the effects of each of the IL-4Ra variants, alone and in combination, on IL-4 responsiveness and the asthmatic phenotype in humans. The applicants propose to introduce missense mutations for each of the IL-4Ra alleles into the human IL-4Ra cDNA, and to transfect them into murine B cells. They then will analyze the transfectants with respect to IL-4 sensitivity and temporal responsiveness to IL-4, specifically related to activation of STAT6 and expression of CD23. They then wish to genotype a cohort of wellcharacterized asthmatic patients and to identify the specific IL-4Ra alleles as markers of asthma risk or severity. Finally, they wish to look at STAT6 activation and CD23 expression in A202.1 murine B cells, as used in the first aim, after cotransfection with combinations of the different allelic variants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: BIOLOGY OF SINGLE ACTIVITY PGH SYNTHASES Principal Investigator & Institution: Funk, Colin D.; Professor; Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: adapted from applicant's abstract): Prostaglandin H synthase-1 (PGHS-1) is the key enzyme in the biosynthesis of prostaglandins, homeostatic lipid mediators in the cardiovascular, gastrointestinal, renal and other organ systems. PGHS-2, on the other
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Glutamine
hand, is a separate gene product, is highly regulated, inducible and is regarded as the form involved in cancer and inflammation. While the simplistic viewpoint of "housekeeping" PGHS-l vs "inducible, pro-inflammatory" PGHS-2 is practical, data is emerging that is not entirely consistent with this hypothesis. PGHS isozymes are bifunctional, with a cyclooxygenase (COX) activity and a functionally linked peroxidase (POX) activity. Non-steroidal antiinflammatory drugs (NSAIDs) act by inhibition of the COX activity, leaving POX activity intact. Substantial data, primarily from in vitro model systems, has implicated the POX component of PGHS in the metabolic activation of xenobiotics and other non-prostaglandin related activities. The main objective of this proposal is to delineate the distinct functions of the COX and POX activities of the PGHS isozymes in carcinogenesis and inflammation using mice with induced mutations created by gene targeting in embryonic stem cells. In Aim 1, COX gene-disrupted mice will be generated by mutation of the aspirin-binding site (serine 530 to asparagine or glutamine), while POX gene-disrupted mice will be created via mutation of the proximal heme ligand (histidine 388 to tyrosine) in Aim 3. The involvement of PGHS POX in the metabolic activation of the nitrofuran compound FANFT, a potent urinary bladder carcinogen, will be analyzed by examination of tumor formation in the mutant mice. Also, the effects of separate COX and POX ablation on skin carcinogenesis using the two-stage DMBA/phorbol ester initiation/promotion protocol and models of inflammation will be assessed in Aims 2 and 4. The COX-disrupted mice, in essence, are perfect in vivo models for complete and selective PGHS-1 arid PGHS-2 inhibition and will be invaluable for studying non-PGHS dependent actions of NSAIDs. Results obtained from this proposal should have broad implications for understanding mechanisms of human cancer and inflammatory disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BLOOD-BRAIN BARRIER TRANSPORT AND ISCHEMIC BRAIN INJURY Principal Investigator & Institution: Keep, Richard F.; Associate Professor; Neurosurgery; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 25-JUL-1996; Project End 31-MAY-2003 Summary: (adapted from applicant's abstract) Because of its juxtaposition to blood, the cerebral endothelium (which forms the blood-brain barrier, BBB) has been thought to be relatively resistant to the effects of cerebral ischemia. However, examination of taurine, glutamine and myo-inositol influx into brain (all Na+-dependent processes) indicate a marked early (<1 hour) reduction in transport during focal cerebral ischemia suggesting that endothelial cell injury could play a role in primary, rather than secondary, ischemic brain damage. This may be particularly the case if efflux from as well as influx into brain are affected since those efflux systems are involved in controlling the concentration of potentially toxic factors in the brain extracelluar space. This proposal, therefore, has two major goals: to determine whether energy-dependent efflux from brain to blood is inhibited during cerebral ischemia (Specific Aims 1 and 2) and to examine whether changes in influx and efflux transport mechanisms at the blood-brain barrier contribute to ischemic brain damage (Specific Aim 3). The cerebral volume of distribution reached by [3H] vinblastine (a P-glycoprotein substrate) and p-[3H] aminohippuric acid (PAH, an organic acid transporter substrate) will be determined following middle cerebral artery occlusion in rat and mouse (Specific Aim 1). Whether an increased volume of distribution with ischemia reflects a change in influx or an alteration in efflux at the blood-brain barrier will then be determined, the latter by examining the effect of
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cerebral ischemia in the absence of BBB P-glycoprotein (the mdr la knock out mouse) or during probenecid-induced inhibition of organic acid transport. Specific Aim 2 will examine the mechanism by which ischemia inhibits efflux, by examining PAH, Lglutamate and methyl aminosobutyric acid efflux (an A-system amino acid transporter substrate) uptake into choroid plexus using ventriculo-cisternal perfusion. Specific Aim 3 will determine the effect of altering specific transporters at the BBB on ischemic brain injury and will examine whether drugs known to ameliorate the effect of reperfusion on blood-brain barrier disruption actually have their effects by altering transport during ischemia. Determining whether early BBB dysfunction should be an alternate therapeutic target early during cerebral ischemia, the finding that there is an inhibition of energy-dependent efflux at the BBB during ischemia has major implications for drug delivery to the injured brain. P-glycoprotein and the organic acid transporter both play a major role in limiting the access of some drugs to the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHANGES IN THE CORNIFIED CELL ENVELOPE IN HPV INFECTION Principal Investigator & Institution: Brown, Darron R.; Medicine; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The mechanism of HPV transmission at the cellular level is poorly understood. Keratinocytes are the target cells for HPV infection. These cells normally exit the cell cycle and undergo the process of differentiation, including expression of proteins that become components of the cornified cell envelope (CCE). Loricrin, involucrin, small proline rich proteins (SPRs), cytokeratins, and other proteins are covalently cross-linked to make up the CCE. The endpoint of differentiation is a layer of flattened, durable, enucleated CCEs that provides the host with barrier protection. HPV infection does not induce cell lysis, and the mechanism of virion escape from infected keratinocytes is not known. The CCE in its normal, durable state would likely hinder virion release. We theorized that a defective CCE would facilitate release of virions. Our studies support this hypothesis. We have shown that HPV 11 infection induces abnormalities of CCEs, and that desquamated, cornified cells from HPV 11 infected tissue are effective transmitters of infection. We have also shown that the HPV 11 El^E4 protein is associated in vivo with the CCE. Our studies of the effects of HPV 11 infection on the CCE demonstrate a markedly reduced amount of Ioricrin and an abundance of SPR3 in HPV 11-infected epithelium. Our studies, performed on fully differentiated epithelium, suggest that HPV 11 gene products cause the defects in the CCE. In addition, our recent studies show that HPV 11 infection reduces Ioricrin transcription. The combined effects of HPV gene products on the CCE may facilitate the escape of virions, and thus increase the efficiency of HPV transmission. In the current proposal, we will test the hypothesis that HPV 11 induces defects of the CCE, and that these defects can be attributed to the effects of the El^E4 and E2 proteins. To test the hypothesis, we will 1) determine if the El^E4 protein is a TGase substrate or an inhibitor of these enzymes; 2) analyze the effects of El^E4 proteins on the composition and biophysical characteristics of CCEs, and 3) examine of the effects of the E2 on expression of the CCE proteins Ioricrin and small proline rich protein 3. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHEMICAL MODELS OF PROTEIN BETA SHEET INTERACTIONS Principal Investigator & Institution: Nowick, James S.; Professor; Chemistry; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-APR-1994; Project End 31-MAR-2004 Summary: beta-Sheet interactions between proteins play a critical role in many biological processes associated with diseases and with normal function. Examples including the binding of Ras and Rap by the serine/threonine kinase Raf in cell signaling and oncogene expression, the dimerization of HIV protease, and the interaction between the CD4 receptor and the HIV viral protein gp120. beta-Sheet formation is also involved in the aggregation of peptides and proteins to form insoluble beta-sheet structures that are associated with a variety of devastating neurological disorders, including Alzheimer's disease, Creutzfeld-Jacob disease and other prion diseases, and Huntington's disease. This proposal seeks to mimic and to disrupt betasheet interactions by using chemical model systems called "artificial beta-sheets." The broad, long-term objectives of this research encompass both the development of drugs for diseases involving beta-sheet formation between proteins (e.g., cancer, Huntington's disease, and Alzheimer's disease) and the development for general strategies for creating compounds that disrupt beta-sheet interactions. The specific aims are as follows: (1) Artificial beta-sheet structures based upon the beta-sheet at the interface of the two halves of the met repressor dimer will be synthesized dimer will be synthesized, and their structures will be studied by NMR and CD spectroscopy. (2) An artificial betasheet designed to mimic the protein G binding region of the Fab portion of the immunoglobulin G will be synthesized, and its interaction with domain III of protein G will be studied by NMR spectroscopy. (3) An artificial beta sheet designed to mimic the beta-sheet interface between Ras proteins and the c-Rafl kinase (Raf) and artificial betasheets that mimic the binding regions of Ras and Raf will be synthesized. Their structures and interactions will be studied by CD and NMR spectroscopy, and the latter two compounds will be evaluated for anti-cancer activity by the NCI using an in vitro 60 human tumor cell line screen. (4) Artificial beta-sheets designed to mimic polyglutamine beta-sheet aggregates, which are involved in Huntington's disease and other genetic neurodegenerative diseases will be synthesized. Their structures will be studied by CD and NMR spectroscopy, and their ability to block polyglutamine beta-sheet aggregation will be determined using an in vitro assay. (5) Artificial beta-sheets designed to block beta-amyloid aggregation will be synthesized, and their abilities to block its aggregation and deposition will be studied using in vitro assays. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTROL OF RENAL GLUTAMINASE INDUCTION DURING ACIDOSIS Principal Investigator & Institution: Curthoys, Norman P.; Professor and Chairman; Biochem and Molecular Biology; Colorado State University Fort Collins, Co 80523 Timing: Fiscal Year 2002; Project Start 01-OCT-1989; Project End 31-MAR-2006 Summary: During chronic metabolic acidosis, increased renal ammoniagenesis and gluconeogenesis from glutamine are sustained, in part, by a cell specific increase in expression of the mitochondrial glutaminase (GA) that results from the selective stabilization of the GA mRNA. Previous experiments identified an 8-base AU- sequence within the 3'- non-translated region of the GA mRNA that functions as a pH-response element (pHRE) when introduced into a chimeric reporter mRNA. This sequence was used as an affinity ligand to purify and identify zeta-crystallin/NADPH; quinone
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reductase as the pHRE-binding protein. The functional characterization of the pHRE was carried out in LLC-PK1-FBPase+ cells, a porcine proximal tubule-like cell line that expresses multiple forms of GA mRNAs. The corresponding porcine GA cDNAs were cloned and sequenced. Only the 4.5-kb GA mRNA contains pHREs that are identical to the sequence identified in the rat GA mRNA and only this form of GA mRNA is stabilized and increased by incubating the cells in acidic medium (Ph=6.9, 10 mM HCO3). Thus this cell lines provides a system to further characterized the molecular mechanism of GA mRNA stabilization and the associated signal transduction pathway. Finally, the 4.50kb GA mRNA is the ortholog of a newly identified isoform of the human kidney-type GA that is generated by alternative splicing of exons within the GA gene. This isoform contains a unique C-terminal domain of unknown function. The specific aims of the proposed research are: to express and characterize the isoforms of the kidney-type GA; to characterize the mechanism of GA mRNA turnover; to characterize the role of zeta-crystallin/NADPH; quinone reductase in the stabilization of the GA mRNA; and to identify the signal transduction pathway that leads to enhanced binding of zeta-crystallin/NADPH; quinone reductase to the pHRE. The results of the proposed experiments should significantly increase the understanding of the molecular mechanism that regulates this essential adaptive response and may provide insight to improve the clinical treatment of chronic acidosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NETWORK
COOPERATIVE
MULTICENTER
NEONATAL
RESEARCH
Principal Investigator & Institution: Lemons, James A.; Pediatrics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 31-MAR-2006 Summary: Indiana University Medical Center has been an active member of the Neonatal Research Network since 1991. Particular strengths of the Indiana Center include a large patient population, design of new randomized trials for the Network, effective enrollment of subjects in Network protocols, eighteen neonatology faculty with extensive experience and expertise in basic and clinical research, an established newborn follow-up program, excellent infrastructure and support staff, and important collaborative research programs with other departments and university centers. Since 1995 (starting year of the second competitive renewal of the Network grant) the faculty within the Section of Neonatal-Perinatal Medicine has had 20 NIH grants and 49 other extramural awards, and has published over 200 manuscripts during that period. Indiana University School of Medicine is the only medical school and the site of the only comprehensive children's hospital in Indiana. The Medical Center serves as the principal referral center for pediatric subspecialty care for the entire state, which has a population of 5.9 million and 87,000 births annually. Further, the Indiana Center expanded in 1997 when Methodist Hospital (a large community hospital with a high risk obstetric service and NICU) merged with the Medical Center. Indiana has a strong record of participation in and contribution to the Neonatal Research Network. During the past four years Indiana enrolled an average of 334 VLBW infants yearly in the generic data base, and 390 infants in 1999 (the largest of any center). Indiana has participated in 12 trials since 1995, contributing 34/235 subjects to the Neonatal Inhaled Nitric Oxide Study 45/170 and 24/115 infants to the two Erythropoietin trials, 3/16 infants to date in the Hypothermia and Hypoxic Ischemic Encephalopathy study, and 65 of 300 to date in the Glutamine Trial. Indiana faculty chaired and developed the Newborn Follow-up Program, the Glutamine Trial, the Magnesium Sulfate Subcommittee and the Protocol
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Review Subcommittee, chaired the GDB Subcommittee, and served on nine other subcommittees. The clinical and basic research of the neonatology faculty is focused on molecular immunology, developmental hematopoiesis, and fetal/neonatal nutrition and metabolism. These research programs lend themselves to ancillary studies of the Neonatal Network; one currently active and six other ancillary studies were designed and initiated by Indiana faculty. Collaborative support has been provided by other investigators, departments and centers when additional expertise and/or resources could benefit Network protocols. Indiana University brings to the Neonatal Network a large patient population, a uniquely balanced program of clinical service and research, and a strong record of participation and accomplishment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CREB BINDING PROTEIN AND GENE REGULATION Principal Investigator & Institution: Ludlam, William H.; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAR-2004 Summary: The cAMP mediated second messenger pathway is a well established model of gene regulation. Within a given cell, many transcription factors are known to interact with and work through the protein kinase A/CREB pathway making integration of multiple signals through common regulatory factors an exceedingly complex phenomenon. The mechanism by which CBP (a CREB co-activator) influences gene regulation is not fully understood, but it is likely that this factor contributes to transcriptional signal integration. There is increasing evidence that this activity may be, in part, due to histone acetylation (HAT) of chromatin that exposes DNA for transcription. The main thrust of this project is to characterize the intrinsic HAT activity of CBP/p300. Four Specific Aims are proposed: (1) CBP/p300 proteins mutated in the putative intrinsic HAT domain (between the bromodomain and the glutamine-rich region of CBP/p300) will be developed to determine and test whether they retain their intrinsic HAT activity. This will also be helpful in mapping the HAT domain. (2) To test whether the intrinsic HAT activity of CBP/p300 for nucleosomes and polynucleosomes is blocked by E1A, since the mechanism by which adenovirus 12S E1A blocks the CBP/p300 co-activator is unknown. (3) To determine whether mutants lose their ability to activate reconstituted chromatin (DNA bound to histones), yet maintain their ability to activate transcription in DNA not bound to histones. (4) To study CBP HAT mutants in developing flies. This lab has previously shown that dCBP rescues CBP-null flies. The inability of CBP HAT mutants to rescue CBP-null flies would be strong evidence that intrinsic HAT activity of CBP (and p300) is critical for in vivo function, and that histone acetylation plays a central role in their gene regulatory function. Gaining insight to the mechanisms of gene activation and silencing has far reaching relevance in the treatment of many diseases including cancers and endocrinopathies. Through a mentored career development plan, the Principal Investigator will gain an enhanced capacity to be productive in the field of molecular biology with a focus on gene regulation. This will be accomplished by conducting the above described research, attending and presenting at local and national seminars and meetings, and participating in courses teaching molecular biology techniques. The proposed mentoring laboratory and institution are rich in intellectual and physical facility resources that provide an excellent environment for the Principal Investigator to transition to independence in the design and implementation of research in the field of gene regulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CRYSTALLIZATION OF ATAXIN-3 Principal Investigator & Institution: Loll, Patrick J.; Biochemistry; Drexel University 3201 Arch Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2006 Summary: (provided by applicant): The polyglutamine diseases are incurable neurodegenerative disorders affecting hundreds of thousands of people worldwide; they are caused by the expansion of normally occurring polyglutamine tracts in proteins. Patients suffer a steady deterioration in motor and cognitive abilities, followed by death. The Aim of this research is to investigate the structural basis of polyglutamine disease, focusing specifically on the ataxin-3 protein. The lengths of polyglutamine tracts in proteins vary within the normal population, but never exceed 35- 40 consecutive glutamines in healthy individuals. Mutations that expand the number of these residues to greater than 40 cause disease. Proteins with expanded polyglutamine regions misfold and aggregate into amyloid fibrils; the aggregation and fibril formation are inextricably linked with cellular dysfunction and death. Expanded glutamine repeats disrupt native protein structure and favor the formation of misfolded states, which can assemble into toxic aggregates. An understanding of this aberrant folding process requires a thorough structural knowledge of both the native and pathological states of the protein. Advances have been made in the characterization of fibril architecture, but no three-dimensional structure is currently available for any polyglutamine protein. This lack of structural information drastically hinders progress toward understanding the molecular basis of polyglutamine disease and developing rational therapies. Ataxin-3 is the causative agent of Machado-Joseph disease, the most common polyglutamine disease. The P. I.'s laboratory is developing ataxin-3 as a model system for studying the misfolding and aggregation of polyglutamine proteins. The structural aspects of this work require crystals of ataxin-3 suitable for X-ray diffraction studies. We therefore have developed a systematic and comprehensive approach to obtaining crystals of full-length and truncated forms of ataxin-3. Three Specific Aims are proposed, namely the identification and crystallization of isolated domains of ataxin-3, the use of rational mutagenesis to improve our ability to grow diffraction-quality crystals, and the use of antibody fragments to prepare Fab-ataxin-3 cocrystals. The molecular understanding of ataxin-3 that will be obtained from this work is a prerequisite for any rational design of therapeutics that will interfere with the protein's aberrant folding and aggregation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DERMATITIS HERPETIFORMIS AND THE MUCOSAL IMMUNE RESPONSE Principal Investigator & Institution: Hall, Russell P.; Professor and Chair; Medicine; Duke University Durham, Nc 27706 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (Verbatim) Dermatitis herpetiformis (DH) is a blistering skin disease characterized by the presence of cutaneous IgA deposits and an associated, almost always asymptomatic, gluten sensitive enteropathy (GSE). The critical role of the mucosal immune response (MIR) in DH has been demonstrated by the observation that, despite the lack of clinical symptoms of GSE in the majority of DH patients, the cutaneous manifestations of DH can be controlled by a gluten free diet. The mechanisms that allow for the development of cutaneous IgA deposits and skin disease yet that prevent the development of symptoms of GSE are not known. The purpose of this project is to characterize the MIR in patients with DH in order to determine the factors
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that prevent the development of clinical signs of gastrointestinal disease yet result in cutaneous deposits of IgA and the development of the cutaneous manifestations of DH. In addition, this project will provide new information regarding factors that may modify and regulate the mucosal immune response to dietary proteins in man and how mucosal inflammation results in inflammatory disease in the skin, joints and other organs. The specific aims of this project are: 1. Determine the antigenic patients with DH and isolated GSE and control subjects using organ culture of specificity and dose response of the T cells in small bowel biopsies from isolated GSE. 2. Characterization of the circulating neutrophils in patient with small bowel biopsies and gliadin peptides, some of which induce disease in DH on gluten containing diets and of the level of cytokine(IL1/TNFa)/chemokine(IL-8) expression in the skin. Skin biopsies from patients with DH from areas predisposed to develop skin lesions (extensor, surfaces) and those areas which normally do not develop skin lesions (upper inner arm) will be analyzed for IL1a, TNF-a, IL-8, and other cyto/chemokine expression during periods of control of the skin disease and no skin lesions and during disease activity. Neutrophils will be analyzed during periods when skin lesions are present and not present to assess the level of activation and expression of cell surface molecules which play a role in neutrophil migration 3. Characterization of the CDR3 region of the T cell Vb families expressed in the small bowel biopsies of patients with DH and of patients with isolated symptomatic and asymptomatic GSE. cDNA from the small bowel of patients with DH, patients with isolated symptomatic GSE and patients with isolated, asymptomatic (treated) GSE and patients with non-gluten sensitive intestinal disease will be analyzed by RT-PCR for the evidence of clonality of the T cells in the gut using CDR3 spectrotype analysis and single strand conformational polymorphisms. These studies will provide insights into the pathogenesis of DH and isolated GSE, the relationship between the MIR and the skin and factors important in controlling the mucosal immune response in man. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYNAMIC MRI AND MRS STUDIES OF FOCAL NEURAL ACTIVATION Principal Investigator & Institution: Gruetter, Rolf; Associate Professor; Radiology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 10-APR-2000; Project End 31-MAR-2003 Summary: (Adapted from applicant's abstract): Many functional imaging techniques are based on measuring changes in cerebral blood flow (CBF), either directly (such as radiotracer methods or perfusion MRI) or indirectly, such as blood-oxygen level dependent (BOLD) functional MRI. These changes in CBF are thought to reflect changes in cerebral metabolic activity, specifically cerebral glucose consumption, CMRglc, which in turn is thought to reflect neuronal activity. The hypotheses of this project are: A) That glutamate-glutamine cycling measured from glutamine labeling reflects neurotransmission, which is increased in focal activation (neuronal spike activity). B) That changes in neurotransmission are matched by changes in metabolic rates, such as flux through (neuronal) pyruvate dehydrogenase (CMRO2), glycolysis and malateaspartate shuttle and that these changes are consistent with BOLD fMRI and perfusion MRI providing a coherent depiction of neurotransmission and its metabolic/hemodynamic correlates. C) Those enzymatic pathways of cerebral glycogen synthesis and breakdown are simultaneously active, such that brain glycogen concentration and cerebral activity levels modulate metabolism. With the following specific aims: 1. To simultaneously measure label incorporation into several distinct
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carbon positions in cerebral glutamate, glutamine and aspartate during 13C labeled glucose infusions with concomitant measurement of tissue glucose and lactate concentrations and combined with perfusion and BOLD fMRI. 2 To develop 13C NMR detection of brain glycogen concentration and metabolism. Significant phosphorylase and synthase activity as reported for brain tissue is expected to lead to label transfer from plasma glucose to brain glycogen when infusing labeled 13C glucose and thus to an observable 13C NMR signal. These aims will be achieved in rat brain using localized 1H and 13C NMR spectroscopy in conjunction with 1H fMRI of BOLD and perfusion. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENTERAL PRECURSORS FOR UREA SYNTHESIS IN HUMANS Principal Investigator & Institution: Gaskins, H R.; Professor; Animal Sciences; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-JUL-2003 Summary: (provided by applicant): The long term goal of the research is to further understand the regulation of nitrogen flow to urea synthesis in humans. A specific focus is on patients with genetic disorders of the urea cycle (UCDs). Currently funded research has shown that inviduals who are heterozygotic for ornithine transcarbamylase and arginino succinic acid synthase deficiency appear to have a partial block in their ability to use glutamine as a nitrogen source for urea synthesis, and that they rely on the hepatic clearance of ammonia generated in the gut to maintain their post prandial N homeostasis. Preliminary results suggest that the administration of sodium phenyl butyrate, a common treatment for UCDs, disrupts branched chain amino acid metabolism. We argue therefore that because of the importance of leucine to protein metabolic regulation, treatment with phenyl butyrate not only diverts N away from urea synthesis, but compromises the regulation of body protein turnover. We hypothesize: Hypothesis 1: Phenyl butyrate, given at therapeutic levels, specifically diverts branched chain amino nitrogen towards glutamine production and away from net tissue protein synthesis. Hypothesis 2: Phenyl butyrate treatment thus inhibits the ability of the body to maintain nitrogen equilibrium, particularly at the restricted protein intakes used in the treatment of UCDs and other metabolic diseases; Hypothesis 3: Patients with UCDs, who are concurrently treated with phenylbutyrate and a low protein diet, will benefit from dietary supplements of branched chain amino acids.To test these hypotheses, we will use stable isotopic tracers of leucine, glutamine, phenylalanine and urea metabolism in studies in normal subjects and individuals with partial or complete defects in urea synthesis. The specific aims will be: Specific aim 1: Determine, in control subjects and heterozygotic carriers of UCDs, the effect of phenyl butyrate on urea, glutamine and branched chain amino acid metabolism. Quantify its effects on body protein turnover. Specific aim 2: Quantify whole body protein turnover and balance in patents with null urea cycle activity who are receiving the conventional regime of phenyl butyrate and a low protein diet. Specific aim 3: Determine the effect of oral branched chain-amino acid supplements on protein, leucine and glutamine metabolism in urea-cycle patients and controls who are receiving phenyl butyrate.The main objective therefore is to use the new clinically oriented information on the regulation of human nitrogen homeostasis, to develop novel nutritional approaches to the treatment of UCDs and other metabolic diseases. In addition it is anticipated that the results will benef it other individuals who have compromised protein metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ENTERAL VS IV FEEDING: EFFECT ON MUCOSAL IMMUNITY Principal Investigator & Institution: Kudsk, Kenneth A.; Surgery; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-MAR-2006 Summary: Hospital acquired pneumonia costs up to 2 billion dollars per year in the United States, and any inexpensive therapy which reduces this septic complication could greatly impact health care costs. Enteral feeding significantly reduces the complications of pneumonia compared with intravenous (IV-TPN) feedings by 60-70 percent in trauma patients. Our experimental and clinical work implicates previously unrecognized defects in mucosal immunity which develop when the intestinal tract is not stimulated with enteral feeding or when surrogates of enteral feeding are not provided. The principal specific immunologic defense at mucosal surfaces is secretory IgA produced by the mucosal-associated lymphoid tissue (MALT). The principal anatomic site for immunologic sensitization of Peyer's patches within the small intestine. Adhesion molecules direct unsensitized immunocytes through the Peyer's patches where these lymphocytes are sensitized and change their own surface integrins. They are then directed to both intestinal and extraintestinal sites, such as the respiratory tract, where they produce IgA against those antigens. The antibody binds to bacteria, preventing their attachment and their ability to infect. This proposal focuses on how route and type of nutrition affects the expression of the specific adhesion molecules, modified MAdCAM-1, unmodified MAdCAM-1, and ICAM-1 which are important in directing unsensitized immunocytes into Peyer's patches. The proposal tests the hypothesis that interaction between these adhesion molecules and their ligands on naive T and B cells are critical in maintaining mucosal immunity in both intestinal and extraintestinal sites. The proposal is designed to test the hypothesis that inhibition of these interactions recreates the defects in in vivo mucosal defenses that are induced when enteral feeding is not provided. It also focuses on previous observations that a specific immunocyte fuel, glutamine, and the enteric nervous system neuropeptide, bombesin, can act as surrogates for enteral feeding and exert beneficial effects upon the MALT in IV-TPN-fed animals by upregulating MAdCAM-1 and ICAM- 1 expression. The experiments are designed to confirm that IgA is a critical element of specific immunity and respiratory defenses against pneumonia with in vivo experiments. These experiments use a monoclonal antibody produced by a hybridoma cell line which is specific for polysaccharide antigen(s) found on a high percentage of clinical isolates of Pseudomonas aeruginosa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FACTOR XLLL ACTIVATION AND SUBSTRATE SPECIFICITY Principal Investigator & Institution: Maurer, Muriel C.; Associate Professor; Chemistry; University of Louisville University of Louisville Louisville, Ky 40292 Timing: Fiscal Year 2002; Project Start 08-JUL-2002; Project End 31-MAY-2006 Summary: In blood coagulation, the enzyme thrombin cleaves fibrinogen, sites for fibrin polymerization are revealed, and fibrin clot formation begins. Activated Factor XIII, a transglutaminase, is responsible for catalyzing the formation of covalent crosslinks between fibrin molecules and in fibrin-enzyme complexes. Thrombin activates Factor XIII by cleaving a peptide sequence that lies across the Factor XIII catalytic site. The thrust of this research project will be to examine in solution the structural features that govern the activation and substrate specificity of Factor XIII. The specific aims are designed to prove the following hypotheses: 1) There is no obvious consensus sequence
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for defining the substrate specificity of Factor XIII for glutamine donating groups. The glutamine containing substrates are hypothesized to interact with the Factor XIII enzyme surface using similar bound conformations with defined flexible and/or solvent exposed regions. Peptides based on natural and synthetic substrates will be examined. 2) The Factor XIII activation peptide segment has components that resemble the fibrinogen Aalpha chain, the thrombin receptor, and PPACK, all of which interact with thrombin. The Factor XIII activation peptide segment is hypothesized to adopt a bound conformation that allows for the most effective interactions with the thrombin surface. An understanding of how unique amino acid positions within this segment participate in binding may lead to the design of Factor XIII enzymes whose degree of activation and optimal target site can be controlled. A model system for these studies is Factor XIII V34L, a common polymorphism that has been correlated with protection against myocardial infarction and is more susceptible to thrombin cleavage than the native sequence. To address these specific aims, a combination of kinetic studies, hydrogen/deuterium exchange followed by MALDI-TOF mass spectrometry, 1D proton line broadening NMR, 2D TOCSY, 2D transferred NOESY, and molecular modeling will be used. Understanding the molecular details of how Factor XIII is activated and how its substrate specificity is regulated is critical considering the role this enzyme plays in increasing the risk of heart disease, stroke, and arteriosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FACTORS THAT MODIFY INSULIN ACTION Principal Investigator & Institution: Buse, Maria G.; Professor; Medicine; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2002; Project Start 01-MAY-1978; Project End 31-MAR-2003 Summary: "Glucose toxicity" accounts for insulin resistance in uncontrolled Type I diabetes (IDDM) and contributes to insulin resistance in Type II diabetes (NIDDM). Sustained hyperglycemia or hyperinsulinemia cause insulin resistance; glucose and insulin act synergistically in down- regulating insulin-stimulated glucose transport. A hypothesis to be tested in 3T3-Ll adipocytes is that glucose/insulin induced glucose transport desensitization reflects altered subcellular trafficking of the glucose transporter, GLUT4, which may involve impaired GLUT4 translocation and inappropriate association of GLUT4 containing vesicles (GCV) with the plasma membrane. Products of the hexosamine synthesis pathway (HNSP) have been implicated in glucose-induced insulin resistance; glutamine-fructose-6-P amidotransferase (GFAT) is the rate limiting enzyme and UDP-N-acetyl glucosamine (UDP-GlcNAc) the major product. The role of HNSP will be tested by examining whether conditions which increase or decrease flux via HNSP augment or mitigate, respectively, glucose induced insulin resistance. O-GlcNAcylation is a reversible process, involving O-glycosylation of proteins on Ser/Thr residues with monosaccharide GlcNAc. It usually involves phosphorylation sites and may be regulatory. Based on preliminary data in muscles of a mouse model of insulin resistance, over-expressing GLUTI in muscle, the hypothesis will be tested that increased flux via HNSP promotes O-GlcNAcylation of critical proteins involved in insulin- stimulated glucose transport. These may include GSV-associated proteins, possibly GLUT4 itself and/or proteins associated with GSV docking and fusion. Since adaptive regulation usually involves multiple sites, we will test the hypothesis that glucose-induced insulin resistance represents in part down-regulation of the insulin receptor (IR) signaling cascade, attempt to identify the major regulatory sites and critically assess the possible contribution of HNSP to the glucose effect. If warranted, the involvement of modulators
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of IR signal transduction, I.E. protein kinase C (PKC) isoforms, and candidate protein tyrosine phosphatases (PTP-ases: PTP-1B, SH-PTP2 and LAR) will be examined. GFAT activity is allosterically regulated by UDP-GlcNAc, and is modulated in vivo in muscle by the hormonal and metabolic milieu. The pre- and post-translational regulation of GFAT expression will be studied in muscles of rodent models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION OF GENES AND PROTEINS IN LEARNING AND MEMORY Principal Investigator & Institution: Eskin, Arnold; Professor and Chair; Biology and Biochemistry; University of Houston 4800 Calhoun Rd Houston, Tx 77004 Timing: Fiscal Year 2002; Project Start 01-JAN-1991; Project End 31-MAR-2004 Summary: The long-term goal of this research is to understand how changes in properties of neurons lead to the formation of memory and subsequent changes in behavior. The behavioral framework of our research is long-term sensitization of the defensive tail, siphon withdrawal reflex of Aplysia. Glutamatergic sensory neurons are key components of the reflex. Long-term presynaptic facilitation (LTF) at the sensorymotor synapse is mainly responsible for sensitization. We hypothesize that a number of properties of a sensory neuron must change in a coordinated fashion to produce LTF and store memory. Thus, we predict that the increase in transmitter release that occurs during LTF should be coordinated with an increase in uptake and synthesis of glutamate. In testing this hypothesis, we found that sensitization training leads to a substantial long-term increase in the Vmax of the high affinity neuronal glutamate transporter. In addition, we found that glutamine uptake was increased suggesting that glutamate synthesis was also increased. These findings provide the basis for molecular and biochemical studies on newly-discovered plastic properties of the sensory neuron. In particular, we will study molecular correlates of memory storage and expression in Aplysia and will extend these findings to research on long-term potentiation in the hippocampus of rats. The proposed research has 4 Specific Aims: Aim 1 is to determine the relationship between increases in glutamate uptake, glutamate synthesis, and behavioral sensitization. Aim 2 is to determine the cellular mechanisms that mediate coordinate regulation of glutamate uptake, synthesis, and long-term facilitation. Aim 3 is to determine whether the mechanisms responsible for the long-term increase in glutamate uptake involve synthesis of transporters and then transport through the ERGolgi-vesicle transport pathway. Aim 4 is to determine the generality of regulation of uptake by studying glutamate uptake during long-term potentiation in the CA1 region of the hippocampus. Deficiencies in glutamate uptake have been implicated in a number of diseases (e.g., ALS, Hodgkin's, Alzheimer's). Glutamate appears to be a remarkably potent and rapidly-acting neurotoxin. This underlines the important role of glutamate uptake in the normal functioning of brains. Our research will help elucidate possible causes for decreased glutamate uptake in these diseases by identifying mechanisms responsible for long-term regulation of glutamate transporters. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTIONAL TRANSPORTERS
CHARACTERIZATION
OF
LEISHMANIA
Principal Investigator & Institution: Landfear, Scott M.; Professor; Molecular Microbiology and Immunology; Oregon Health & Science University Portland, or 972393098
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Timing: Fiscal Year 2002; Project Start 01-SEP-1991; Project End 31-MAY-2006 Summary: (provided by applicant): The objective of this proposal is to characterize at the molecular level several transporters from Leishmania and trypanosomes that mediate the uptake of important nutrients from the hosts. These nutrients include glucose which is an major source of metabolic energy in the insect stage of the life cycle, purines which are essential nutrients that the parasites cannot synthesize de novo, and amino acids which are both catabolized to generate energy and utilized in anabolic pathways such as protein synthesis. In the first aim, the physiological functions of the LdGT1 and LdGT2 glucose transporter isoforms of L. donovani will be probed by generating null mutants and analyzing their phenotypes. These studies may elucidate the functional differences between the flagellar membrane LdGT1 and the pellicular plasma membrane LdGT2. In the second aim, the permeation pathway of the L. donovani adenosine/pyrimidine nucleoside transporter LdNT1.1 will be probed by a combination of cysteine-scanning mutagenesis and sulfhydryl group chemical modification. These studies have been guided by the detection of two distinct point mutations that inactivate LdNT1.1, possibly by altering amino acids that line the permeation pathway. The TbNT8 transporter from Trypanosoma brucei, whose mRNA is expressed exclusively in insect stage parasites, is closely related in sequence to other well characterized nucleoside transporters, but it's function remains to be defined. This third aim will characterize a strongly developmentally regulated nucleoside transporter and allow its comparison to other bloodstream-specific nucleoside transporters. The final aim will functionally characterize a novel amino acid transporter from L. major that is related in sequence to mamrnalian N-type amino acid permeases that mediate the uptake of glutamine, and histidine, essential amino acids for growth of Leishmania parasites. These studies will initiate the molecular analysis of amino acid transporters in Leishmania. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GAMMA-CRYSTALLIN MODIFICATIONS /MECHANISMS OF LENS OPACI Principal Investigator & Institution: Pande, Jayanti; Research Associate; Physics; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2003; Project Start 01-JUN-1994; Project End 31-MAY-2008 Summary: (provided by applicant): Our long-term objectives are to understand how specific post-translational chemical modifications and genetic mutations of the gammacrystallin proteins lead to lens opacity. We hypothesize that not all protein modifications are deleterious - only those that lead to increased light scattering. Our strategy designed to test this hypothesis is as follows: We will model the cataractogenicity of a given modification or mutation of a gamma-crystallin in vitro, by introducing the required change into the protein and determining the effect on the formation of protein aggregates, liquid droplets containing protein-rich and protein-poor phases, and protein crystals (i.e., protein-derived condensed phases). Protein modifications that enhance the formation of such condensed phases (all of which lead to increased light scattering) will be potentially cataractogenic. We will compare the phase behavior (liquid-liquid and solid-liquid phase separation) of native and modified gamma-crystallins to evaluate if a given modification enhances or suppresses the formation of condensates. In parallel, we will also examine protein structure and conformation using biochemical and spectroscopic methods (chromatography, HPLC, gel electrophoresis, Raman spectroscopy, circular dichroism, fluorescence, and x-ray crystallography). We propose the following Specific Aims: (1) Evaluate which physiologically relevant chemical
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Glutamine
modifications of the 7 crystallins found enhance the formation of condensed phases - (1 a) Examine the effect of modifications of cysteine residues (i.e., thiolations) with (i) glutathione (ii) cysteine (iii) cysteinylglycine and (iv) gamma-glutamyl cysteine, (1b) Examine the effect of deamidation of asparagine and glutamine residues, and (1c) Examine the effect of truncations of the 7 crystallin polypeptide chain (2) Evaluate which of the genetic variants of the gamma-crystallins enhance the formation of condensed phases - (2a) Determine the mechanisms of opacification due to mutant proteins expressed from gamma-crystallin genes associated (in the literature) with human or animal model cataracts, (2b) Determine what effect the mutant proteins expressed from gamma-crystallin gene variants due to single-nucleotide polymorphisms, have an effect on opacification. This work is designed to provide plausible mechanisms for lens opacification due to gamma-crystallin modifications and mutations. Understanding these mechanisms is an essential first step towards the development of reagents to delay the onset of opacities due to (a) the commonly encountered age-onset cataract and (b) the rare nuclear opacities of genetic origin seen in children and young adults. In view of the recent evidence in the literature that suggests that age-onset cataract may have a genetic component, the studies proposed here have the potential for predicting the susceptibility of individuals towards this disease due to normal variants of the gamma-crystallins in the general populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC STUDIES OF GLUTAMINE SYNTHETASE IN BACTERIA Principal Investigator & Institution: Kustu, Sydney G.; Associate Professor; Plant and Microbial Biology; University of California Berkeley Berkeley, Ca 94720 Timing: Fiscal Year 2002; Project Start 15-SEP-1986; Project End 31-MAY-2007 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GI MUCOSAL BARRIER IN HEALTH AND SURGICAL DISEASE Principal Investigator & Institution: Hagen, Susan J.; Associate Professor; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2003; Project Start 01-JAN-1977; Project End 31-MAY-2008 Summary: (provided by applicant): The overall aim of the proposed work is to understand how Helicobacter pylori (HP) infection causes mucosal damage in the stomach, with special emphasis on the fundic region of the stomach. The investigators plan to study how HP infection impairs tight junction integrity and wound repair after injury (restitution) to result in increased mucosal permeability. HP-induced mucosal damage of the stomach is important because it is a major initiating factor in the pathogenesis of HP disease, including inflammation, atrophy of fundic epithelial cells including parietal and chief cells, metaplasia, and progression to gastric cancer. Because HP infection has far-reaching implications in terms of benign and malignant disease, mechanisms that underlie the initiation of mucosal damage, repair after damage, and protection against damage are important and timely. Three hypotheses will be tested. 1) HP infection increases mucosal permeability because either HP or inflammatory cells decrease tight junction integrity. This hypothesis will be tested by investigating how HP sonicates or cytokines secreted during a type 1 T-helper (Th1) response affect the phosphorylation and membrane association of proteins associated with the tight junction. 2) HP infection increases mucosal permeability because ammonia, a cytotoxin produced during HP infection, inhibits restitution. This hypothesis will be tested by
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investigating the effects of ammonia on activity of the H+/lactate transporter, MCT1, and on basolateral K+-channel activity. 3) L-glutamine (Gln) supplementation decreases mucosal permeability by inhibiting the Th1 response and cytokine-induced decreases in tight junction integrity that occur during HP infection. This hypothesis will be tested by determining whether L-Gln supplementation inhibits the Th1 cytokine response to preserve tight junction integrity in a mouse model of disease. The proposed investigations follow a logical sequence from previous studies in this laboratory, which have provided a structural framework for our knowledge of mucosal injury, protection against injury, and rapid epithelial repair (restitution) as they relate to maintenance of the gastric mucosal barrier in health and surgical disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCONEOGENESIS IN VERY LOW BIRTH WEIGHT INFANTS Principal Investigator & Institution: Sunehag, Agneta; Assistant Professor of Pediatrics; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: Improvements in the management of premature infants have resulted in a dramatic increase in their survival. Previously, nutritional management was not of high priority in very low birth weight (VLBW) infants since most died early in life. As a result, our refinement of the nutritional management of these surviving infants has lagged behind the advancements in cardio-respiratory therapy. VLBW infants are susceptible to hypoglycemia; thus, to provide sufficient calories and to prevent hypoglycemia, glucose is routinely infused at high rates (approximately 60 mumol/kg min, twice that of measured glucose turnover rates in these infants) as part of standard total parenteral nutrition (TPN) which frequently results in hyperglycemia. Like hypoglycemia, hyperglycemia can have significant short and long term adverse impact on their outcomes. The specific focus of the present application is to determine the individual and collective roles of the substrates provided in standard total parenteral nutrition on glucose production from glycogenolysis and gluconeogenesis (GNG) and glucose utilization. These studies will determine: a. Whether VLBW infants receiving TPN who are normoglycemic suppress their glucose production completely and those who are hyperglycemic have incomplete suppression of glucose production and/or reduced glucose utilization; b. When VLBW infants are supplied glucose at a reduced rate (17 mumol/kg min): 1. Do i.v. lipids (IntralipidR) increase GNG and glucose production and if so is this the result of providing energy for GNG through betaoxidation or providing glycerol as a 3-carbon precursor; 2. Whether glycerol increases GNG and glucose production in a dose dependent fashion in VLBW infants; 3. Whether i.v. amino acid solution (TrophAmineR) and/or the gluconeogenic amino acids, glutamine and alanine, will increase GNG and glucose production; and 4. Whether glucagon will increase GNG and glucose production from endogenous and exogenous substrate sources. The ultimate aim will be to utilize this information in designing alternative mixtures of constituents (substrates and possibly hormones) which will decrease the risk of both hypo- and hyperglycemia in these infants, by utilizing the infants' gluconeogenic pathway, while providing sufficient substrate to sustain normal growth and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTAMINE AMIDOTRANSFERASES AND PARTNER ENZYMES Principal Investigator & Institution: Smith, Janet L.; Professor; Biological Sciences; Purdue University West Lafayette West Lafayette, in 479072040
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Glutamine
Timing: Fiscal Year 2002; Project Start 01-FEB-1990; Project End 31-JAN-2003 Summary: Glutamine amidotransferases are "complex" enzymes with two different catalytic domains, each contributing to the catalysis of a single biochemical reaction. The family of sixteen enzymes catalyzes the transfer of amide nitrogen from glutamine (glutamine catalytic domain) to a variety of acceptor substrates (acceptor catalytic domain). Crystal structures have been determined for two amidotransferases of de novo purine biosynthesis. The structures of glutamine PRPP amidotransferase (GPATase) and GMP synthetase are prototypes for the two homologous families of glutamine catalytic domains, the Ntn and Triad families, respectively. The acceptor domains of both enzymes also represent homologous enzymes families, the phosphoribosyltransferases and the N-type ATP pyrophosphatases. Results from these first structures of amidotransferases have changed thinking about the enzyme family and led to new direction for future experiments. The most important new discovery of this work has been the means by which Ntn amidotransferases couple catalysis between glutamine and acceptor domains. The enzyme creates a channel for NH/3 between glutamine and acceptor active sites. Signal transduction between catalytic sites is triggered by substrate binding in the acceptor domain and involves formation of the NH/3 channel and activation of the glutamine domain. The proposed studies will investigate control and operation of the NH3 channel in GPATase and determine whether Triad amidotransferases also channel NH/3 between active sites. The product of GPATase is extremely unstable, and there is indirect evidence for channeling to GAP synthetase, the next enzyme of the purine biosynthetic pathway. This possibility will be investigated by structural studies of GAP synthetase and by mutagenesis experiments. The significant observations of the first two amidotransferases will be extended to other members of the enzyme family. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTAMINE METABOLISM IN THE HUMAN NEWBORN Principal Investigator & Institution: Kalhan, Satish C.; Professor; Pediatrics; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Glutamine, an endogenously synthesized amino acid, has been variously considered "essential" or "conditionally essential" during acute illness and in very low birth weight (VLBW) infants. Several investigators have proposed the use of supplemental glutamine in VLBW babies in order to accelerate adaptation to extrauterine environment and recovery from related neonatal illness. However, there are no data actually quantifying changes in glutamine metabolism in relation to ontogeny or acute illness in full term and prematurely born infants. The specific aims of these studies are to examine the systemic and splanchnic metabolism of glutamine, and its relation to whole body protein/nitrogen and urea kinetics in the neonate. Since glutamine is synthesized de novo via a cataplerotic reaction of the tricarboxylic acid cycle from alphaketoglutarate and glutamate, it is hypothesized that its metabolism will be closely linked with the anaplerotic flux of substrates such as glucose and amino acids into the tricarboxylic acid cycle. Glutamine also serves as an important respiratory fuel for the enterocytes and the lymphocytes. It is hypothesized that enterally administered glutamine will be utilized locally in the splanchnic compartment in growing infants when the enterocytes (and lymphocytes) are proliferating. Furthermore, during neonatal adaptation and during recovery from acute illness in the low birth weight baby, glutamine will not be locally metabolized and will bypass the splanchnic compartment. These hypotheses will be examined by quantifying
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the kinetics of glutamine in zombination with measurements of the transamination of branched chain amino acids, protein turnover and urea synthesis. Stable isotopic tracers and gas chromatograph-mass spectrometric methods will be employed. These studies will systematically examine the interrelationship between the transamination of an essential amino acid, leucine, and the de novo synthesis of a dispensable amino acid, glutamine, during the critical period of ransition to extrauterine environment and during growth, and will provide a metabolic basis for nutritional management of low birth weight infants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUTAMINE:FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE FORNIDDM Principal Investigator & Institution: Teng, David H.; Deltagen Proteomics, Inc. 615 Arapeen Dr, Ste 300 Salt Lake City, Ut 84108 Timing: Fiscal Year 2002; Project Start 04-JUN-2002; Project End 31-MAY-2003 Summary: We have developed a transdominant genetic methodology for isolating peptide, protein or RNA factors (collectively called peturbagens) that modulate biochemical targets within a cell to alter its phenotype. Because it is genetic approach, it can be applied in both the classical forward mode (from phenotype to genotype) to reverse mode (from gene to function). The main goal of the proposed Phase I research is to validate human glutamine: fructose-6-phosphate amidotransferase (hsGFA1), the rate- limiting enzyme that catalyzes the first reaction in the hexosamine pathway, as a pharmacologic target for insulin resistance. This will be achieved by the following steps: (1) Isolating peptides that bindhsGFA1 using a modified yeast two hybrid assay. (2) Determine which peptides inhibit hsGFA1 activity by examining the conditional lethality of gfa1-/pGaI-hsGFA1+ yeast, that are viable despite to loss of the endogenous gfa1 gene due to rescue by galactose- regulated expression of hsGFA1. Inhibitors of hsGFA1 in these yeast cells will be cytotoxic. (3) Expressing the hsGFA1 peptide inhibitors in insulin-responsive cultured HepG2 hepatic cells and3T3-L1 adipocytes and ascertaining effects on GFA activity and the hexosamine pathway, as well as cellular glucose transport. The successful completion of Phase I will enable downstream studies of gsGFA1 inhibitors in mouse models of type 2 diabetes and obesity. PROPOSED COMMERCIAL APPLICATIONS: Perturbagen technology offers a novel way to probe and validate the function of a protein within a cell or animal. Proof that inhibition of hsGFA1 is capable of reversing insulin resistance in mammalian cells, or mouse models of diabetes and obesity, would open the flood gates for the search of chemical antagonists of the enzyme. If so, the peptide binders themselves may be useful in a highthroughput screen involving the displacement of the peptide binder from hsGFA1 by a small molecule. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTAMINE'S ROLE IN CARDIOPROTECTION FROM CARDIAC BYPASS Principal Investigator & Institution: Wischmeyer, Paul E.; Anesthesiology; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The Principal Investigator, Dr. Wischmeyer has the long-term goal of pursuing independent clinical investigation in the field of nutritional pharmacology. Receipt of a Mentored Patient-Oriented Research Career Development
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Award will facilitate the growth of Dr. Wischmeyer's investigative skills and experience by expanding his knowledge of clinical research design and the use of molecular and metabolic assay techniques in human research. The learning objectives set out in this proposal, combined with the support of his mentor, Dr. Robert Eckel and the critical environment within the Department of Anesthesiology, the Department of Surgery, and the Training Program in Clinical Sciences at the UC, will foster Dr. Wischmeyers's progression to independent lines of investigation into the clinical applications of nutrition to clinical states of tissue injury and critical illness. The specific aims of this proposal will extend previous pre-clinical research by Dr. Wischmeyer demonstrating a protective effect of the amino acid glutamine (GLN) on myocardial ischemia/reperfusion (I/R) injury. This proposal aims to evaluate in a randomized, controlled clinical trial the effect of pre-operatively administered, oral GLN on patients undergoing elective coronary artery bypass grafting (CABG) in which cardiopulmonary bypass is employed. Four immediate goals for the trial are defined: 1) Determine the effect of GLN on myocardial tissue injury. Comary effluent and plasma will be collected and analyzed for troponin, CKMB analysis. 2) Determine the effect of GLN on human atrial tissue heat shock protein content. Right atrial appendage tissue will be harvested from patients undergoing CABG surgery and analyzed for heat shock protein 72 and 27 content (Western analysis). 3) Determine the effect of GLN on enhancement of measures of metabolism in human atrial tissue. Right atrial appendage tissue will be harvested from patients undergoing CABG surgery and analyzed for tissue metabolism magnetic resonance spectroscopy (MRS). These measurements will include tissue ATP, ATP/ADP ratio, NAD/NADH content, lactate, glutamine, glutamate, and reduced glutathione content. 4) Determine the effect of GLN on post-operative cardiac function and overall patient outcomes. Data will be collected on cardiac function (cardiac output), occurrence of arrhythmias, need for vasopressor therapy, length of post-operative ventilation, ICU stay; and survival trends. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DENTICOLA
H2S
PRODUCTION
AND
VIRULENCE
OF
TREPONEMA
Principal Investigator & Institution: Chu, Lianrui; Research Associate Professor; Orthodontics; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2004; Project Start 01-SEP-2000; Project End 31-DEC-2007 Summary: This application is an extension of current research examining the association between H2S production and virulence of Treponema denticola. T. denticola has been identified as an important member of a consortium of microorganisms as etiologic in the initiation and progression of periodontal diseases. In addition, the existence of volatile sulfur compounds produced at destructive sites is a characteristic feature of periodontal diseases, with H2S as a major compound in this family. Nevertheless, the metabolic pathways used to produce H2S are not well understood. Previous studies suggest that glutathione present in host cells can be a substrate for H2S production. Recently, we have shown that T. denticola has the capacity to utilize glutathione as a substrate to produce high levels of H2S. We have identified three enzymes that are required for the successful metabolism of glutathione: gamma-glutamyltransferase (GGT), cysteinylglycinase (CGase), and cystalysin. GGT converts glutathione into Cys-Gly and glutamic acid; CGase catalyze Cys-Gly to Cys and glycine; and cystalysin digests Lcysteine into H2S, ammonia, and pyruvate. We have also demonstrated that the addition of cystalysin and L-cysteine resulted in apoptosis of HGF and PDL cells and
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that glutathione was essential for lesion formation by T. denticola in an animal model. Based on these and other studies, three Specific Aims are proposed using biochemical, molecular genetic, and cell biologic studies to address the hypothesis that these three metabolic enzymes play a key role in T denticola pathogenesis. Specific Aim 1: To molecularly characterize the genes and proteins involved in converting glutathione to H2S. Specific Aim 2: To genetically characterize, by gene inactivation, the enzyme pathway of T. denticola that produces H2S from glutathione. Specific Aim 3: To measure the effects of the H2S/NH3 producing pathway on T. denticola virulence in vitro and in vivo. This application is designed to provide both seminal and critical information about the enzyme pathway of T. denticola to produce H2S from glutathione. The outcomes will elucidate the mechanisms of action that each member of the enzyme pathway plays in the virulence capacity of T. denticola. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEPATIC DRUG ELIMINATION IN PREGNANCY Principal Investigator & Institution: Vore, Mary E.; Professor and Director; Toxicology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 30-SEP-1979; Project End 31-MAY-2006 Summary: (provided by applicant): This proposal focuses on the effects of estradiol and its metabolites on the function and expression of Mrp2 (ABCC2), the ABC transporter that mediates the biliary excretion of glucuronide and glutathione conjugates from the hepatocyte into bile. The proposal builds on our findings that 1) Mrp2-mediated transport of estradiol-17Beta-(Beta-D-glucuronide) (E217G) is essential for its cholestatic activity, 2) E217G causes endocytic retrieval of Mrp2 from the canalicular membrane that coincides with decreased bile flow, and 3) expression of Mrp2 protein, but not Mrp2 mRNA, is decreased in pregnancy. Aim 1 will test the hypothesis that transport of cholestatic E217G and the choleretic estradiol-3-glucuronide (E23G) by rat Mrp2 and human MRP2 is mediated by overlapping but non-identical substrate binding sites. We will use an Mrp2/MRP2 baculovirus expression system in Sf9 cells and probe the substrate binding sites of E217G vs E23G. We will also determine if women with intrahepatic cholestasis of pregnancy have polymorphisms in MRP2 that alter their transport of E217G vs E23G. Aim 2 will test the hypotheses that A) E217G causes endocytic retrieval of Mrp2 and other transporters critical to bile formation from the canalicular membrane leading to inhibition of flow, and B) agents that protect against cholestasis do so by either inhibiting Mrp2 transport of E217G or prevention of transporter retrieval. We will use confocal immunomicroscopy to monitor endocytic retrieval of transporters from and their exocytic insertion into the canalicular membrane. Aim 3 will characterize the changes in Mrp2 expression in pregnancy and test the hypotheses that A) estrogens mediate the decreased hepatic Mrp2 expression in pregnancy, B) Mrp2 is subject to transcript-specific translational control conferred by regulatory elements in the 5' or 3' untranslated regions of Mrp2 mRNA and C) pregnancy and estrogens increase the degradation of Mpr2 protein. We will use polysomal distribution analysis of Mrp2 mRNA, translation assays in HepG2 cells and determine the degradation half-life of Mrp2 protein in control, pregnant, and estrogentreated rats. Significance: Characterization of the mechanisms by which estrogens decrease Mrp2/MRP2 function and expression can lead to 1) improved drug therapy for women in pregnancy, 2) development of therapeutic measures to increase MRP2 function in cholestatic liver disease, and 3) methods to screen for cholestatic toxicity in drugs under development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IL-8 IN CHONDROCALCINOSIS Principal Investigator & Institution: Bryan, Ru L.; Veterans Medical Research Fdn/San Diego Foundation of San Diego San Diego, Ca 92161 Timing: Fiscal Year 2003; Project Start 15-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): Calcification of the pericellular matrix in articular cartilage is highly prevalent in osteoarthritis (OA) and aging. The deposited crystals of calcium pyrophosphate dihydrate (CPPD) and/or hydroxyapatite (HA) can be released from the cartilage matrix and can trigger inflammation and promote the expression of connective tissue degrading enzymes, thereby contributing to further cartilage degradation. The expression of C-X-C chemokines including IL-8 and its receptors CXCR-1 and CXCR-2 has recently been demonstrated in chondrocytes, and these mediators all are up regulated in OA cartilage in vivo. Our preliminary studies demonstrated that IL-8 induces MMP-13, and promotes features of hypertrophic differentiation (type X collagen expression and transglutaminase activation) associated with heightened matrix calcification in vitro in articular chondrocytes. Base on our new data on IL-8 signaling and function in leukocytes and articular chondrocytes, we propose to advance understanding of how IL-8 signaling via CXCR1 and/or CXCR2 transduces hypertrophy and matrix calcification in articular chondrocytes. We will test the following hypothetical model: 1) Activation of p38 MAPK is essential for induction of the features of hypertrophic differentiation, matrix calcification and MMP-13 by IL-8 in articualr chondrocytes. 2) Pyk2 tyrosine kinase, associated with a Src family tyrosine kinase, plays a central role in activation of p38 MAPK in mediating such effects of IL-8 in articular chondrocytes. 3) CXCR1 and CXCR2 signal differentially to transduce the stimulatory effect of IL-8. 4) Phospholipase C (PLC) transduces CXCR1 and CXCR2 signaling to induce intracellular Ca2+ increase and protein kinase C (PKC) activation, which in turn, activate Pyk2 and alpha5beta1 integrin, respectively. 5) FAK, activated through alpha5-beta1 integrin, and Pyk2 differentially mediate CXCR1 and CXCR2 signaling to induce hypertrophic differentiation, matrix calcification and MMP-13 in articular chondrocytes. The completion of this study has the potential to provide a foundation for novel chemokine and signal transduction-based therapeutic strategies for treatment of chondrocalcinosis in OA and aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INHIBITION OF PROSTATE SPECIFIC MEMBRANE ANTIGEN Principal Investigator & Institution: Berkman, Clifford E.; San Francisco State University 1600 Holloway Ave San Francisco, Ca 94132 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: Prostate cancer remains the most common male malignancy and the second most common cause of cancer-related mortality in most Western societies. The incidence of prostate cancer and corresponding mortality rates vary strikingly among ethnic, racial, and national groups with noteworthy high rates among African Americans. The identification of an upregulated and strongly expressed antigenic marker on prostate cancer cells, namely prostate specific membrane antigen (PSMA), has attracted a great deal of attention as a target for immunotherapy. More recently, it has been reported that PSMA possesses at least two specific enzymatic activities; the hydrolytic cleavage and liberation of glutamic acid from both gamma-glutamyl derivatives of folic acid and the neuropeptide NAAG (Nacetylaspartylglutamate). Although these enzymatic activities have been clearly identified, questions of medical interest remain to be answered for PSMA. Two such questions are: "What is the role of PSMA on the surface of prostate
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cancer cells?" and "How would inhibiting PSMA affect the growth, proliferation, or regulation of prostate cancer cells?" Although the proposed research will not immediately address these questions, it is anticipated that the results of this work will provide the investigators with suitable tools to study these issues in future studies. Furthermore, it is likely that the enzymatic activity of PSMA could be exploited for chemotherapeutic strategies, one of which being the inhibition of its activity by small molecule inhibitors. The overall objective of the proposed work is to develop potent and selective inhibitors for PSMA. This will be accomplished by first conducting substrate studies to identify optimal structural frameworks for enzyme recognition. These frameworks will then be utilized in the design and development of a first generation of phosphonopeptide inhibitors of PSMA. The most promising and potent of these inhibitors will be then further elaborated with binding probes to identify and exploit auxiliary binding sites on the enzyme leading to enhanced inhibitory potency. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTEGRIN-TRANSGLUTAMINASE ASSOCIATED AND CELL ADHESION Principal Investigator & Institution: Belkin, Alexey M.; American National Red Cross Rockville, Md 20855 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Interactions of cells with their neighbors and the surrounding extracellular matrix are critically important for normal physiological and pathological processes. The major goal of this project is to characterize the role of the newly identified integrin-binding adhesion coreceptor, tissue transglutaminase (tTG), in cell adhesion and adhesion-dependent cellular functions, including signaling and assembly of fibronectin (Fn) matrix. A number of deletion and point mutants, as well as chimeric constructs containing swaps with the a subunit of Factor XIII, a structural homologue of tTG which does not interact with integrins or Fn, will be employed to map the integrin- and Fn-binding sites on tTG. Dominant negative tTG mutants which retain integrin binding, but fail to interact with Fn, will be used in various assays designed to analyze the adhesive function of tTG. We will quantitate an increase in adhesion strength generated by integrin-associated surface tTG. A proposed bridging function of tTG in cell adhesion as a mediator of integrin-Fn interaction will be defined. We will test the ability of surface tTG to alter the overall pattern of cell-ECM recognition. The effects of tTG on integrin activation, clustering and cytoskeletal association will be studied. Since our initial data indicate the ability of tTG to alter activation of Rho and Rac GTPases, we will separate and define the roles of cell surface and cytoplasmic tTG in integrin-mediated and direct activation of Rho and Rac GTPases. Then, the contributions of Rho, Rac and their common downstream target, myosin II, to the unique phenotype of cells that express high levels of surface tTG, will be determined. We will also continue to analyze mechanisms of stimulation of Fn assembly by integrin-bound tTG. A hypothesis will be tested that binding of Fn to tTG or dual interaction of Fn with integrins and tTG exposes a cryptic self-assembly site in modules I9III1 of Fn, and thereby stimulates fibril formation. Finally, the effect of association with integrins on the ability of tTG to crosslink Fn will be examined. Together, the proposed experiments will provide novel insights into the role of tTG in cell adhesion, adhesion-mediated signaling and Fn matrix formation. Furthermore, our studies will define how adhesive and signaling functions of integrins are regulated by their association with tTG. Ultimately, this acquired knowledge will advance our understanding of basic mechanisms of cell-matrix interactions.
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Glutamine
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INVESTIGATIONS ON GLUCONEOGENESIS Principal Investigator & Institution: Brunengraber, Henri; Professor and Chair; Nutrition; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2004 Summary: (Scanned from the applicant's description) Gluconeogenesis plays a major role in the metabolic alterations, which threaten the health and the life of diabetic patients. We seek to expand our understanding of the dysregulation of gluconeogenesis in type I diabetics by a combination of clinical investigations, development of new techniques for measuring gluconeogenesis, and basic science studies in animals. Over the next three years, we plan to achieve the following specific aims: 1. To test the usefulness of measuring the hepatic flux ratio (pyruvate carboxylase)/(pyruvate dehydrogenase) as an index of liver insulinization in clinical investigations of type I diabetes. This ratio will be determined noninvasively via the 13C-labeling pattern of urinary phenylacetylglutamine. We plan to compare the gluconeogenic status of normal subjects and type I diabetics (kept in good control by an infusion of insulin, acutely deprived of infused insulin, and poorly controlled). The study will involve administering [3-13C]pyruvate, 2H2O [6,6-2H2]glucose, and phenylbutyrate, and assaying (i) the '3C-labeling pattern of urinary phenylacetylglutamine, (ii) fractional gluconeogenesis via the 2H enrichment ratio C5/C2 of plasma glucose, and (iii) the turnover of glucose. 2. To work out new procedures to determine fractional gluconeogenesis from the 2H enrichment ratio C5/C2 of plasma glucose in subjects ingesting 2H2O. The procedure will be applicable to small samples from children, and to glucose samples labeled with '3C in addition to 2H. 3. To characterize, in perfused livers from normal rats and diabetic BB rats, the involvement of ATP-citrate lyase in the gluconeogenic pathway, specifically in the transfer, from mitochondria to the cytosol, of oxaloacetate derived from lactate (which itself was formed during Con cycling and muscular exercise). We hypothesize that an active citrate cleavage pathway persists in the liver under non-lipogenic conditions such as starvation. This process contributes to the recycling of lactate to glucose and to the detoxification of xenobiotics via acetylation. We hope that the data of our investigations will help to devise new strategies for improving the treatment of type I diabetic patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: KETOGENIC DIET AND BRAIN AMINO ACID METABOLISM Principal Investigator & Institution: Yudkoff, Marc L.; Chief; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAY-2004 Summary: (from applicant's abstract) The ketogenic diet is often used to control seizures in children who are resistant to antiepileptic drugs. The mode of action is totally unknown. The PI hypothesizes, based on their preliminary data, that one reason the ketone bodies (3-OH-butyrate and acetoacetate) are so effective in controlling seizures is that they increase the brain concentration of GABA (gamma amino butyric acid), a major inhibitory neurotransmitter, and lower the concentration of aspartate, an excitatory compound. Ketone bodies bring about these changes because they sharply reduce the rate of transamination of glutamate to aspartate. As a result, more glutamate becomes available for the synthesis of GABA. In astrocytes, more glutamate becomes available to the glutamine synthetase pathway. This results in increased synthesis of glutamine, a
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highly effective precursor to GABA. They propose to test this hypothesis by developing a rat model of the ketogenic diet. The model involves the prolonged (from weeks to months) feeding of rat pups with either an artificial rat milk or an isocaloric amount of a high fat (ketogenic diet). They will use stable isotopes, e.g., 15N and 13C to measure rates of glutamate metabolism to GABA, aspartate and glutamine. Mass spectrometry is used as an analytical tool with which to measure stable isotopic abundance in amino acids and tricarboxylic acid cycle intermediates. The three specific aims are: (1) To test the above hypothesis; (2) To characterize the ketogenic diet: Is high fat feeding necessary, or could ketone bodies alone be fed? How rapidly do amino acid changes develop? How sustained are they? Are changes more pronounced in less mature animals?; and (3) To determine whether the ketogenic diet can ameliorate seizures in a standard rat model of epilepsy, and whether this therapeutic effect is associated with changes of amino acid levels that mimic those noted in control animals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LENS CATARACTOGENESIS
MEMBRANE
IN
RELATION
TO
HUMAN
Principal Investigator & Institution: Takemoto, Larry J.; Professor; Division of Biology; Kansas State University 2 Fairchild Hall Manhattan, Ks 665061103 Timing: Fiscal Year 2002; Project Start 01-JUN-1979; Project End 31-MAY-2007 Summary: (provided by applicant): Although posttranslational modifications of lens proteins play a causative role in biogenesis of human senile cataracts, surprisingly little is known concerning the identity of specific amino acids that are modified in these lenses. Nonenzymatic deamidation of asparagine and glutamine residues is probably the most prevalent modification occurring in the human lens, and studies from other tissues have suggested that resistance to deamidation is a general property of stable proteins. The central hypothesis of this proposal is that the aged human lens contains gamma/beta crystallins with very low rates of deamidation, and that if deamidation does occur, it could result in deleterious effects to the lens, such as the formation of high molecular weight aggregates, low molecular weight cleavage products, and eventual cataract. To identify and quantitate deamidation, we have developed a novel approach involving the use of synthetic peptide standards, HPLC, mass spectral analysis and Nterminal sequencing. This methodology will be used to identify and quantitate deamidation of specific residues from the high molecular weight aggregate and low molecular weight cleavage products, as well as total proteins from dissected nuclei of human cataractous and aged-matched normal lenses. Molecular modeling will be used to correlate known structural properties of crystallins, with their observed rates of deamidation. Finally, human gamma/beta crystallins containing specific residues found to be deamidated will be expressed in a recombinant system and characterized by various biochemical and biophysical methods. Together, this project will identify and quantitate deamidation of specific residues of gamma/beta crystallins in the aging normal and cataractous human lens, followed by determination of the consequences of these modifications upon the stability and structural properties of the expressed deamidated proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIFESPAN HYPOGLYCEMIA
NEURONAL/GLIAL
METABOLISM
DURING
Principal Investigator & Institution: Turner, Dennis A.; Professor; Surgery; Duke University Durham, Nc 27706
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Glutamine
Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The central hypothesis of this project focuses on protective strategies for enhancing neuronal metabolism during and after short-term hypoglycemia. Several related mechanisms will be studied using physiological and mitochondrial imaging techniques in acute hippocampal slices, following hypoglycemia. In particular, we will directly assess neuronal-glial metabolic inter-relationships by analyzing whether the "lactate shuttle" is altered as a function of age. We will also directly measure the presence or absence of mitochondrial permeability transition as a function of age. Because slice metabolism varies as a function of slice oxygenation, age of the tissue and slice conditions (i.e., interface versus submerged slice conditions), direct oxygen tension measurements will be performed in the tissue using a Clark-style oxygen microelectrode at the same depth as the electrical recordings. The oxygen tension monitoring will ensure that metabolic substrate provision is controlled appropriately within the slice. Neuronal-glial metabolic interactions will be analyzed using glial poisoning with fluoroacetate to estimate direct neuronal contribution to glycolysis and aerobic metabolism, by substituting lactate and pyruvate. Pyruvate will be assessed as a potential treatment for preventing hypoglycemic damage. Occurrence and prevention of mitochondrial permeability transition with these stresses will also be assessed, using cyclosporin A and newer analogs such as N-Me-VaI-CSA. Analysis of these mechanisms which lead to enhanced susceptibility to neuronal damage following hypoglycemia are likely to lead to enhanced treatment. Mechanisms of neuronal injury are expected to vary depending on the duration and severity of the hypoglycemia, and the age of the animal from which hippocampal slices were harvested. These in vitro slice models of hypoglycemia will contribute greatly to the understanding of neuronal metabolism, and particularly the metabolic interactions between neurons and glia as a function of lifespan. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LONG-TERM IMPACT AND INTERVENTION FOR DIARRHEA IN BRAZIL Principal Investigator & Institution: Guerrant, Richard L.; Professor; Internal Medicine; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 01-MAY-1989; Project End 31-JUL-2004 Summary: Having defined the magnitude, major new etiologies, key novel mechanisms and short-term impact of persistent diarrheal illnesses and even certain "asymptomatic" enteric infections in a model collaboration and cohort of children born into active prospective surveillance in an urban shantytown in Northeast Brazil, we are now have a unique opportunity to define for the first time the long-term DALY (disability adjusted life years) impact of early childhood enteric infections on nutritional status defined by anthropometry, physical activity and fitness, and cognitive function over extended periods (even years later). We postulate, based on our short-term impact data, that the greatest long-term impact will occur in children with persistent diarrheal illnesses and in those with low height-for-age Z (HAZ) scores. Having also shown the potential shortterm benefits of a new glutamine-based oral rehydration and nutrition therapy (ORNT) and of vitamin A (with studies of zinc pending) on speeding the repair of damaged intestinal barrier function, we can now determine the potential long-term benefits of glutamine-based ORNT, with vitamin A and zinc therapy (targeting children with persistent diarrhea or reduced HAZ, as noted above). We shall also examine the intermediate (ie 1- 6 months) and long-term (greater than 6 months) effects of specific emerging enteric infections we have found to be important, enteroaggregative E. coli,
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and Cryptosporidium parvum. Coupled with our new developments of stable glutamine derivatives, the above data on full long-term DALY impact of persistent diarrhea, enteric infections and malnutrition, and the data on benefits of glutaminebased ORNT with vitamin A and zinc will ultimately allow us to calculate a much more meaningful cost-effectiveness (in "dollars per DALY averted) of selected treatment of high risk children (ie any with a persistent diarrheal illness that extends greater than 14 days, or a height for age Z score of less than 0.5). This model, longstanding collaboration and prospective field cohort surveillance will also enable the use of molecular tools currently being developed to define the epidemiology and microbiology of such newly recognized major agents as enteroaggregative E. coli as well as opening new opportunities to train both US and international scientists in highly relevant bench and field investigation. This pioneering work builds on our unique opportunity to define for the first time the potentially huge (developmental and economic) burden of early childhood enteric infections, as well as holding promise for demonstrating a key intervention targeted at the most vulnerable subset of the population in greatest need. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: M TUBERCULOSIS GLUTAMINE SYNTHETASE EXPORT & INHIBITION Principal Investigator & Institution: Horwitz, Marcus A.; Medicine; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-1998; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract): Tuberculosis is the world's leading cause of death from a single infectious agent. The emergence of multidrug resistance tuberculosis poses a major new threat to the public health, giving new urgency to research aimed at combating this ancient scourge. The development of new strategies to prevent and treat tuberculosis requires more basic knowledge about the key molecules of the organism that allow it to infect the host. One such key molecule is glutamine synthetase. M. tuberculosis glutamine synthetase has three remarkable and very important characteristics, all discovered in the investigator's laboratory during the past three years. First, it is one of the major extracellular proteins and its export by the bacterium is highly correlated with pathogenicity, i.e., pathogenic mycobacteria secrete the enzyme but nonpathogenic mycobacteria do not. Second, its export, which does not involve a signal peptide, is determined by its amino acid sequence, making it an ideal model protein for studying signal peptide-independent protein export. Third, inhibition of its extracellular enzyme activity inhibits its growth both in broth and within human macrophages, making it an extraordinarily accessible and promising target for new antibiotic development. This project has two major goals. First, the investigators seek to use molecular biological approaches to map which amino acids govern the export of M. tuberculosis glutamine synthetase. Second, building upon their studies of a parent compound that inhibits the glutamine synthetase activity and growth of M. tuberculosis and upon their collaborative studies of the high resolution 3-dimensional structure of M. tuberculosis glutamine synthetase, they hope to develop more active entities than the parent compound and thereby to develop a new antibiotic against M. tuberculosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MCH MODULATION OF NEUROTRANSMISSION IN THE LH AREA Principal Investigator & Institution: Gao, Xiao-Bing; Child Study Center; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047
32
Glutamine
Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): In this proposal, the role and mechanism of melanin-concentrating hormone (MCH) in the regulation and function of the lateral hypothalamus (LH) at the cellular level will be addressed. In feeding regulation LH plays a key role and has been considered as a feeding center. The regulation of food intake is crucial in energy- balance homeostasis. Unbalanced energy accumulation leads to obesity. MCH is a cyclic 19-amino-acid peptide. A substantial body of evidence from systemic, morphological and molecular biological studies suggests that MCH is involved in feeding regulation. However, there is little evidence as to the physiological role of MCH in LH neurons at the cellular level. Also there is little evidence as to how MCH and other neuropeptides interact in LH neurons. Furthermore, there is little data about the cellular physiology as well as properties of neurons and neuronal organization in the LH area. In this proposal, electrophysiological methods (including extracellular recording, whole-cell voltage and current clamp recording), immunocytochemistry and digital calcium imaging will be employed in cultured neurons and acute hypothalamic slices from rats. The chief hypothesis to be tested is that MCH acts as an inhibitory neuropeptide to modulate neuronal activity in the LH. The following hypotheses will be examined: 1. MCH depresses the activity-dependent gene transcription. 2. MCH inhibits the function of voltage-dependent calcium channel subtypes via distinct signaling pathways. 3. MCH depresses glutamatergic and GABAergic synaptic transmission in the LH slices. 4. Characterization and organization of MCH responding neurons in LH slices will be documented. This proposal will begin to bridge the gap between molecular research and systemic studies on the regulation of feeding to benefit those suffering from obesity and obesity-related diseases. The applicant's previous work in characterizing the cellular physiology of the newly discovered neuropeptide hypocretin/orexin is the first step in his journey to pursue his long-term goal of understanding neurotransmission in the LH. The funding of this research proposal is important for the applicant to continue this course. A career development plan is also documented in this proposal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISM CYTOTOXICITY
OF
ANDROGEN
RECEPTOR
INDUCED
Principal Investigator & Institution: Lafevre-Bernt, Michelle; Buck Institute for Age Research Novato, Ca 94945 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2005 Summary: (provided by applicant): Kennedy's disease, or spinal and bulbar muscular atrophy (SBMA) is caused by an expansion of CAG repeats (which encode for glutamine) in the 5' end of the coding region of the androgen receptor (AR) gene. It is one of nine polyglutamine repeat diseases that cause the selective loss of neurons in selective regions of the brain. Seven of the polyglutamine repeat proteins, including AR, are substrates for caspases. Therefore it is important to understand the role of caspase activation and proteolysis in polyglutamine repeat-mediated cell death. The specific aims of this proposal are: (1) To determine if the toxic fragments generated by caspasemediated proteolysis of AR interact with full-length AR and disrupts its function. (2) To determine which protein interaction domains are required for the caspase-7 and AR apoptosome-like complex. (3) To determine which initiator caspases are important in androgen receptor induced cell death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MENTORED DEVELOPMENT
PATIENT
ORIENTED
RESEARCH
33
CAREER
Principal Investigator & Institution: Escolar, Diana M.; Associate Professor of Neurology & Pedia; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2002; Project Start 10-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): The applicant is a neurologist and has extensive clinical experience in pediatric and adult neuromuscular diseases. This award will allow her to obtain the training and mentoring to become an independent clinical investigator focusing on neuromuscular disorders. The educational plan includes didactic courses covering epidemiology, statistics, clinical trial design and health policies. DMD is a relatively common fatal genetic disease in children, with equal incidence throughout the world. The goal of this research is to conduct therapeutic human clinical trials with chemicals shown to improve muscle strength in the mdx. The aims of the proposed research plan are: 1) to conduct a double-blind, placebo-controlled, three-arm clinical trial of creatine and L-glutamine in patients with DMD and to assess the effect of these compounds on muscle strength as measured by manual muscle testing (MMT), quantitative muscle testing (QMT) and other functional measurements. Aim 2 is to conduct a double-blind, placebo- controlled clinical trial of coenzyme Q10 (CoQ10) in patients with DMD to assess its effects on: a) muscle strength, measured by QMT, compound Medical Research Council (MRC) score and functional measures; b) exercise capacity, to be measured by a fatigability protocol; and c) quality of life, to be measures by the Child Health Questionnaire. Aim 3 is to validate the specificity of the pediatric QMT system measuring maximal voluntary isometric contraction sequentially in children with DMD. The studies will be conducted at Pediatric Clinical Research Center (PCRC) at the Children's National Medical Center (CNMC), satellite to Georgetown General Clinical Research Center (GCRC). Three cores of the PCRC will be involved: the Biostatistics Core, the Genetics Core Laboratory and the Bioanalytical Core Laboratory. In addition, to increase the statistical power of this study, the applicant has assembled an international collaborative group that will conduct identical protocols and submit the data to the study center at CNMC. Future studies will test several other drugs with potential to improve muscle strength in DMD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METABOLISM AND EXCITABILITY IN RODENT HIPPOCAMPUS Principal Investigator & Institution: Williamson, Anne D.; Assistant Professor; Neurosurgery; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2007 Summary: (provided by applicant): Both excitatory and inhibitory synaptic transmission rely on the supply of glutamate. Glutamate is synthesized de novo from glucose and also recycled through the glutamate-glutamine cycle between neurons and astrocytes. GABA used for synaptic transmission is also dependent on neuronal-glial cycling as GABA is synthesized from glutamate which can enter interneurons either via uptake or through glutamine. The main goal of this proposal is to test the broad hypothesis that cellular excitability is intimately tied to the status of glutamate-glutamine-GABA cycling and specifically that GABAergic transmission is more sensitive than excitatory transmission to disruption in cycling during periods of sustained neuronal activity because of the added energy-dependent steps needed for the synthesis of GABA. In Specific Aim 1 we will interrupt cycling a several different levels including blockade of the synthetic enzymes of glutamine, glutamate and GABA as well as by blocking
34
Glutamine
glutamine uptake. The effect of these metabolic inhibitors on synaptic inhibition will be examined physiologically. In Specific Aim 2, we will use mass spectometry to measure the changes in the levels of glutamate, glutamine and GABA induced by alterations in neurotransmitter cycling in both the tissue and in the bathing medium to address the time-dependent changes in transmitter levels. In Specific Aim 3 will use 13C isomer spectroscopy to assess the effect of those compounds that cross the blood brain barrier (the GS inhibitor methionine sulfoximine and the glutamine transporter MeAIB) on glutamate-glutamine-GABA cycling in control animals. These experiments should provide important data on the regulation of normal synaptic transmission as well as an understanding of the pathology of a number of neurological disorders where changes in neural energetics have been seen including epilepsy, ALS and Huntington's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODELS OF SBMA MOTOR NEURON DEGENERATION Principal Investigator & Institution: La Spada, Albert R.; Assistant Professor; Laboratory Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: X-linked spinal and bulbar muscular atrophy (SBMA or Kennedy's disease) is a progressive neuromuscular disorder characterized pathologically by degeneration of lower motor neurons. In 1991, expansion of a CAG trinucleotide repeat was identified in the coding region of the androgen receptor (AR) gene of SBMA patients. In addition to SBMA, seven other neurodegenerative disorders are caused by CAG repeat expansions that encode elongated polyglutamine tracts. Molecular and genetic studies of the CAG/polyglutamine repeat diseases suggest that the polyglutamine tract expansion has a toxic gain-of- function effect, the basis of which remains unknown. The purpose of this grant proposal is to determine the molecular basis of neuronal cell death in SBMA. To achieve this goal, we have initiated studies aimed at recapitulating AR polyglutamine neurotoxicity in mice and in cell culture. For producing an in vivo model of SBMA, we have generated AR yeast artificial chromosomes (YACs) carrying 100 CAG repeats. These AR YACs have been introduced into the mouse germline by fusing yeast cells carrying the AR YACs with mouse embryonic stem (ES) cells. In addition to an in vivo model of SBMA, we are attempting to develop in vitro models of AR polyglutamine neurotoxicity. We have demonstrated cellular toxicity of mutant AR expression constructs in HEK-293T cells, a non-neuronal cell line. We are attempting to extend this finding to motor neuron-like cell lines, MN-1 and NSC-34, and are also establishing primary cultures of cortical, hippocampal, and spinal motor neurons. Once we have produced accurate in vivo and in vitro models of SBMA, we will examine the role of apoptotic pathways in SBMA pathogenesis by evaluating whether caspase activation and/or p53 participate in AR polyglutamine neurotoxicity. We will use our in vivo and in vitro models to determine what functions of the AR protein are required for SBMA disease pathogenesis. Animal and cell culture models of AR polyglutamine neurotoxicity will allow us to identify alterations in gene expression in diseased motor neurons and cell lines by performing microarray expression comparisons. As SBMA, amyotrophic lateral sclerosis and autosomal spinal muscular atrophy all show motor neuron cell death, any toxic factors or degenerative pathways that we identify in our studies may be relevant to these and other motor neuron diseases. In addition to allowing us to track the molecular events that lead to neuronal cell death, animal and cell culture models of SBMA will allow us to design novel treatments and test potential therapies for this motor neuron disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ESOPHAGEAL CA
MOLECULAR
35
CORRELATES--OXALIPLATIN/5FU/XRT,
Principal Investigator & Institution: Pendyala, Lakshmi; Roswell Park Cancer Institute Corp Buffalo, Ny 14263 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Provided by applicant): There is a pressing need for new agents in the treatment of esophageal cancer and to identify intratumoral molecular markers predictive for tumor response to chemotherapy. Although cisplatin/5-fluorouracil (5FU) plus radiation (XRT) is considered standard therapy for patients with locally advanced esophageal cancer, distant tumor recurrence, representing chemotherapy failure, is the rule. Moreover, the toxicity profile for cisplatin may be disabling. Oxaliplatin (OXP) a diaminocyclohexane platinum complex has a more manageable toxicity profile. Clinical/pre-clinical data suggest OXP-5FU synergy; mechanisms behind the synergy are not understood. Prior studies have shown that response and survival after therapy with 5FU (colon cancer) or 5FU/cisplatin (gastric cancer) are inversely associated with thymidylate synthase (TS), dihydropyrmidine dehydrogenase (DPD) and the excision repair cross-complementing-1 (ERCC-1) gene expressions. Studies of OXP resistant cell lines indicate that resistance is multifactorial, as evidenced by lowered drug accumulation, increased glutathione and decreased DNA-Pt adducts. Resistant cells also had elevated expression of gamma-glutamyltranspeptidase (gamma-GT) and ERCC- 1 genes. Thus, the underlying hypotheses in this application are: A) molecular markers within a primary esophageal tumor will predict sensitivity or resistance to chemotherapy, B) oxaliplatin affects 5FU by lowering TS gene expression and C) pharmacokinetics (PK) of OXP will influence the changes in gene expression. The specific aims of this study are to determine: 1) the intra-tumoral mRNA expression of TS, DPD, gamma-glutamylcysteine synthetase (gamma-GCS), gamma-GT, multidrug resistance associated protein-2 (MRP-2), ERCC-1 and xeroderma pigmentosum A (XPA) at pretreatment, 1 week after OXP alone, and after 1 cycle (with 5FU/radiation), exploring the relationship between these expression levels and response/resistance to treatment; 2) the PK of ultrafilterable platinum on day 1 when OXP is given alone and again on day 15 a week after combination with 5FU + XRT and 3) the relation between PK and changes in intratumoral gene expression and 4) maximum tolerated dose (MTD), dose limiting toxicity (DLT), and the potential therapeutic responses to OXP when given with continuous infusion 5FU + XRT. The gene expression studies will be carried out using real time quantitative RT-PCR (Taqman( r )) assays in endoscopic biopsies. Preliminary results indicate that the regimen is tolerable, the proposed gene expression measurements can be carried out using endoscopic biopsies and changes in gene expression are being detected for some genes during therapy. The long term objectives are to identify a drug combination for better clinical outcome and to identify molecular parameters predictive for response or resistance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MRS STUDIES OF CORTICAL GABA IN DEPRESSION Principal Investigator & Institution: Sanacora, Gerard; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): I have been fortunate to work in stimulating environments that have afforded me substantial opportunities to engage in research training throughout my graduate (M.D., Ph.D.) and residency training. In July,
36
Glutamine
I will continue my training an additional year with the Daniel X. Freedman Clinical Neuroscience Fellowship at Yale University. However, without support from a K08 award, I would be required to assume substantial clinical responsibilities in order to support my salary when I join the Yale faculty in July, 1999. I have designed this K08 award to enable me to pursue a comprehensive five-year research-training Plan. This plan will provide me with the background and skills necessary to become an independent investigator-using novel magnetic resonance spectroscopy (MRS) techniques. I would like to apply these techniques to the study of GABA and glutamate neurotransmission related to the pathophysiology and treatment of affective disorders. Over the past two years I have developed basic skills in-proton-MRS (1H-MRS). We have produced exciting preliminary data describing reductions in cortical GABA associated with depression, and elevation of cortical GABA levels following electroconvulsive therapy (ECT). I propose to continue these investigations with two aims. 1) To fully characterize both GABAergic and glutamatergic systems in affective disorder disease states. (Years 1-3) and 2) To use pharmacological probes along with [13C]-MRS to examine possible pathophysiological mechanisms related to amino acid neurotransmitter regulation in depression. In order to advance the use of MRS applications in the study of affective disorders, I have identified several key areas where I will require additional training including: 1) nuclear magnetic resonance, 2)1 neurochemistry, kinetic modeling, and related neuroimaging technologies, 3) clinical and basic neuropharmacology applicable to affective disorders research; and 4) clinical trials methodologies. I believe my background in the basic sciences will enable me to complete the rigorous training plan outlined in this application. This training along with continued practical application of the technology under the co-mentorship of Drs. Rothman and Krystal should thoroughly prepare me for a career as an independent investigator using MRS technology to study brain neurochemistry. This novel line investigation will open previously inaccessible areas of research, with a broad range of future applications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTICENTER NETWORK OF NEONATAL INTENSIVE CARE UNITS Principal Investigator & Institution: Tyson, Jon E.; Professor Pediatrics; Pediatrics; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: The PI is Jon Tyson, MD, MPH, is the Michelle Bain Distinguished Professor of Medicine and Public Health, Director of the Center for Population Health and Evidence-Based Medicine, and a Professor of Pediatrics, Obstetrics, and Epidemiology at UT Houston. Th Co-PI is Kathleen Kennedy, MD who is an Associate Professor of Pediatrics and the Director of the Perinatal Epidemiology Program UT Houston was added to the Network in 1998 when the PI and Co-PI moved from UT Southwestern. UT Houston provides: A. A large and growing patient population. A total of 9,000 total births and 350 VLBW infants are projected this year for our 2 teaching hospitals: Memorial Hermann Hospital (a private hospital with an expanding referral base including 9 hospitals in the Memorial Hermann system [3 staffed by our Ob. Faculty]) and Lyndon Baines Johnson Hospital (a large county hospital with an increasing population). UT Houston's enrollment in the Glutamine Trial exceeds that for all but 2 of the other 13 Network centers. B. Strong, and highly supportive leadership at UT Houston. The Dean (Max Buja, MD) recruited Dr. Tyson to promote clinical research. The Ob. Chairman (Larry Gilstrap) is a perinatal investigator and Network consultant.
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The Pediatrics Chairman (John Sparks, MD) is a neonatologist and Network advocate. The Neonatology Director (Fernando Moya, MD) is Hermann Physician of the Year and skilled in conducting clinical research, eliciting hospital support, and augmenting enthusiasm for Network studies. C. An experienced and highly committed PI and Co-PI. Dr Tyson has been a PI for 13 years; Dr. Kennedy, Co-PI for 9 years and acting PI for 1 year. In the past 4 years, they have been an author on 16 Network publications, 3 as 1st author; 3 as 2nd author, and 1 as 3rd author. (4 of these were published in New England Journal or JAMA.) In moving to Houston, Dr. Tyson petitioned NICHD to include both UT Southwestern and UT Houston (rather than UT Houston only) in the Network and has served as PI for both. He has helped the Co-PI at UT Southwestern to apply as PI there for the next funding cycle. Dr. Tyson has involved multiple other faculty and fellows in the Network including Robert Lasky, PhD a developmental psychologist with expertise in neural processing; Terri Major-Kincade, MD,MPH, 1st recipient of the Network Specialized Clinical Investigator Development Award; and Martin Blakely, MD a pediatric surgeon whose K23 proposal (Dr. Tyson as mentor) is focused on Network studies. D. Methodological and multidisciplinary expertise. The Network can further advance the methods of clinical research and enrich the evaluation of important neonatal issues. Dr. Tyson is an epidemiologist and neonatologist, the PI for the NIHfunded Clinical Research Curriculum, and Director of the Master's Degree Program in Clinical Research to start here. The Center for Population Health and Evidence- Based Medicine that he directs includes 9 faculty with expertise in clinical or population-based epidemiology, biostatistics, developmental psychology, health care economics, and/or bioethics; 3 of these faculty are now involved in Network studies. John C. Sinclair, MD, an eminent neonatologist, clinical epidemiologist, and Network advisor, will join the Center Jan. 2001. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NMR STUDIES OF GABA METABOLISM AND REGULATION IN VIVO Principal Investigator & Institution: Behar, Kevin L.; Professor; Neurology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 22-JUL-1996; Project End 31-JUL-2005 Summary: (Verbatim from the Applicant's Abstract) For the last 10-15 years our laboratory has had a major role in the development and use of new spectroscopy and imaging techniques in vivo to study the regulation of pathways of brain glucose metabolism. Over the last 4 years of this grant we reported a number of important findings which indicate that release of glutamate and GABA from neurons and their cycling between neurons and glia has a major influence on brain energy metabolism and that the isoforms of a key enzyme of GABA synthesis, glutamic acid decarboxylase (GAD) mediate different proportions of total GABA synthesis. Our central hypothesis is that specific GAD isoforms and supply routes of glutamate carbon play key roles in regulating GABA synthesis and GABA neurotransmitter cycling. We propose the following specific aims: 1a) Determine the relationship between the rates of GABA synthesis, GABA neurotrasmitter cycling, and glutamate/glutamine cycle over a wide range of cortical metabolic activity. 1b) Assess the role of cofactor interaction and phosphorylation of the GAD isoforms in the regulation of GABA synthesis and GABA/glutamine cycling flux. 2) Investigate the role of GAD isoforms in regulation of GABA cycling flux through the two glutamate precursor pathways using GABAtransaminase inhibition and GABA elevation to selectively alter GAD isoform composition. 3) Quantitate the key metabolic pathway fluxes that supply glutamate
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Glutamine
precursors for GABA synthesis and GABA/glutamine cycling. 4) Determine the relationship between vesicular and non-vesicular GABA, precursor glutamate pathways, and GAD isoforms using diffusion-sensitized MRS in vivo. Using Magnetic Resonance spectroscopy (MRS) and 13C-labeled isotopes in vivo, and enzymatic assays in vitro with pharmacological and molecular biological interventions, we will examine the role of GAD isoforms and glutamate precursors in GABA synthesis and GABA neurotransmitter cycling The uniqueness of this project derives from i) the combination of the these techniques, ii) the track record of the investigator in addressing such questions using MRS, and iii) it complements ongoing clinical investigations of GABA and glutamate metabolism in epilepsy and neuropsychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NONVESICULAR GABA RELEASE VIA GABA TRANSPORTER REVERSAL Principal Investigator & Institution: Richerson, George B.; Associate Professor; Neurology; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: As one of the most common neurological diseases in this country, epilepsy affects approximately 2.5 million Americans. Drugs used to treat epilepsy often target neurotransmission, and their design and use would be advanced by a better understanding of the mechanisms of neurotransmission. It is commonly assumed that neurotransmitters are only released by synaptic vesicle fusion. However, our recent studies suggest that GABA transporters reverse during seizures, resulting in GABA efflux. This "nonvesicular" GABA release inhibits neurons, and is also the target of a new class of anticonvulsants, including gabapentin and vigabatrin. The current proposal extends this work by using rat neurons to address the following unanswered questions. What is the source of nonvesicular GABA release: neurons or glia? This will be examined using neuronal vs. glial specific GABA transporter antagonists in pure neuron, pure glia or mixed cultures. How do changes in cytosolic [GABA] affect vesicular GABA release? The effect on vesicular and nonvesicular GABA release of increasing or decreasing cytosolic [GABA] will be compared. How commonly is nonvesicular GABA release modulated by anticonvulsants? The effects on nonvesicular GABA release of pregabalin, topiramate, levetiracetam, and tiagabine will be studied. How ubiquitous is nonvesicular GABA release? The role of nonvesicular GABA release will be studied in brain slices from the hippocampus, neocortex, striatum, cerebellum and medulla. Does the glutamate transporter reverse as easily as the GABA transporter? The threshold for nonvesicular glutamate release will be determined. We propose that the GABA transporter reverses as part of a fail-safe negative feedback system. If the glutamate transporter reversed so easily, it would lead to runaway excitotoxicity. The proposed experiments are designed to answer fundamental questions about the newly recognized role of the GABA transporter in inhibition of seizures, and the mechanism of action of anticonvulsants. A complete description of GABA transporter function should help define the pathophysiology of epilepsy, and lead to a better understanding of how and when the new anticonvulsants should be used. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHOSPHOLIPASE DIFFERENTIATION
C-GAMMA-1
IN
MEDIATING
Principal Investigator & Institution: Bikle, Daniel D.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545
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Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2008 Summary: Phospholipase C-gamma1 (PLC-gamma1) plays a critical role in calcium induced differentiation in part because of its ability to maintain high levels of intracellular calcium (Cai) through the provision of two important second messengers, inositol tris phosphate (IP3) and diacyl glycerol (DG). IP3 stimulates the release of calcium from intracellular stores by activating its receptor IP3R, a calcium channel in the endoplasmic reticulum and Golgi, whereas DG activates the classic and novel protein kinases C. Preliminary findings from our laboratory have demonstrated two pathways mediating calcium-induced activation of PLC-gamma1 in normal keratinocytes: one via src kinases and the other via phosphatidylinositol 3 kinases (PI3K). Furthermore, in normal keratinocytes much of the PLC-gamma1 colocalizes in the cell with other members of the calcium-signaling pathway including the calcium receptor (CaR), the IP3 receptor (IP3R), and the Golgi calcium pump (ATP2C1) suggesting an intimate interaction between PLC-gamma1 and the molecular regulators of intracellular calcium levels. Accordingly we propose the following hypothesis: PLC-gamma1 plays a central role in the mechanism by which calcium induces keratinocyte differentiation. Calcium activates PLC-gamma1 through src kinases and PI3K and promotes its interaction with regulators of Cai stores such as the IP3R and Golgi calcium pump (ATP2C1) that provide for the sustained increase in Cai essential for differentiation. To test this hypothesis we propose 4 specific aims. In the first two aims, we will explore the mechanisms by which calcium activates PLC-gamma1 in normal cells. In the third aim we will examine whether PLC-gamma1 activation by src kinases and PI3K is required for its interaction with IP3R and ATP2C1. In these aims we will compare the effects of calcium to those of EGF, which also activates PLC-gamma1 but stimulates proliferation rather than differentiation, with the expectation of finding differences between the two with respect to the mechanism of PLC-gamma1 activation. Because differentiation in vitro does not achieve the final product, namely the formation of a competent permeability barrier, in the fourth aim we will develop an in vivo model to analyze the impact of selectively deleting PLC-gamma1 expression with respect to the program of differentiation leading up to the development and regulation of the permeability barrier. Calcium signaling and calcium induced differentiation in the keratinocytes from these animals will also be studied in vitro to evaluate the comparability with earlier studies of human keratinocytes in which the PLC-gamma1 gene was knocked out by antisense techniques. These studies will increase our understanding of keratinocyte differentiation and may provide therapeutic targets for diseases in which epidermal differentiation is abnormal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--BIOCHEMISTRY AND FUNCTION OF A NOVEL SECRETED KERATINOCYTE PROTEIN Principal Investigator & Institution: Ariizumi, Kiyoshi; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2006 Summary: The barrier function of skin against noxious environmental agents is provided primarily by the cornified cell envelop (CE) in the outer portion of the epidermis. The CE is a protein complex tightly assembled by transglutaminase (TGasemediated cross-linking of several structural proteins (e.g., involucrin). Using a signal sequence trap method, we have identified a novel secreted protein, KCS-1, that contains a leucine- zipper-like structure which is known to be responsible for dimer- formation of some transcription factors. KCS-1 is expressed specifically by keratinocytes (KC) of
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Glutamine
epithelial tissues, localized to the CE in normal human epidermis. It is up-regulated in the skin of psoriatic patients with inflammation and microbial infection, and displays anti-proteinase activity. These findings suggest that KC secrete some KCS-1 proteins (as a dimer form) into the epidermal extracellular space, some of which are trapped into the CE by TGase and some remain as free dimers inside cells. Environmental stress and tissue damage induce abundant expression of proteinase in the epidermis that is likely to be a major mediator to delivery danger (or stress) signals to KC. We thus hypothesize that KCS-1 expression is inducible by environmental stresses and it functions as a intraand extracellular proteinase inhibitor to quench the potentially damaging effects of these harmful proteinases. Having characterized the biochemical and structural properties of KCS-1 in the previous one year funding period, we now propose to better illustrate functional properties of KCS-1, a new secreted inhibitor, in the proposed second year of funding. Functional characterization of KCS-1 will lead us to a better understanding of KC mechanisms that protect the skin and internal organs from environmental stresses and tissue damage. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PILOT--REGULATION OF RENAL PYRUVATE DEHYDROGENASE DURING ACIDOSIS Principal Investigator & Institution: Harris, Robert A.; Professor of Pharmacology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: The objective of this work is to establish the importance of regulation of the pyruvate dehydrogenase (PDH) complex in the kidney in maintenance of acid-base balance. Activity of the pyruvate dehydrogenase complex is regulated by covalent modification. Phosphorylation and inactivation of the complex is catalyzed by four pyruvate dehydrogenase kinase (PDK) isoenzymes; dephosphorylation by two pyruvate dehydrogenase phosphatase (PDP) isoenzymes. Unique regulatory properties of these isoenzymes and differences in their levels of expression in different cell types provide tissue specific control of the activity of the pyruvate dehydrogenase complex. The basis for this proposed work is our preliminary data indicating that two of the PDK isoenzymes, PDK2 and PDK4, are increased in the kidney by metabolic acidosis. We propose therefore that increased expression of these PDKs results in inactivation of pyruvate dehydrogenase complex, which promotes generation of new bicarbonate by the kidney. Our working hypothesis is that alterations in the expression of the PDK2 and PDK4 isoenzymes cause hyperphosphorylation and therefore inactivation of pyruvate dehydrogenase complex in kidney during metabolic acidosis. The hypothesis will be tested by: (a) determining the effects of acute and chronic metabolic acidosis and alkalosis on activity state of the PDH complex and the expression levels of its kinases and phosphatases in rat kidney; (b) determining whether the compensatory mechanism for metabolic acidosis is abnormal in the kidney of the PDK4 null mouse; and (c) establish factors and mechanisms that regulate expression of PDK2, PDK4, and PDP2 in the kidney. The findings are expected to provide new insight with respect to an important compensatory mechanism for life threatening metabolic acidosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PILOT--SYSTEM NEUROTRANSMISSION
A
TRANSPORTERS
IN
41
GLUTAMINERGIC
Principal Investigator & Institution: Varoqui, Helene; Louisiana State Univ Hsc New Orleans New Orleans, La 70112 Timing: Fiscal Year 2002; Project Start 23-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): We have cloned and functionally identified cDNAs encoding the proteins SAT1 and SAT2 that are the first members of the system A family of Na+-dependent neutral amino acid transporters. Transport of system A substrates, such as glutamine, and alanine, in many cell types are highly regulated since these amino acids play important roles in neurotransmission, energy generation and in nitrogen metabolism. The identification of SAT1 and its neuron-specific expression is an unexpected discovery and suggests an important and unique role of SAT1 in synaptic transmission. The electrogenic uptake of these amino acids in peripheral organs is mediated by SAT2, and in neurons, SAT2 may provide alanine, as a nitrogen donor to alpha-ketoglutarate, to generate a metabolic pool of glutamate. Since glutamine is a critical precursor for neurotransmitter glutamate via the glutamate-glutamine cycle, it is reasonable to propose to test the hypothesis that these transporters play key roles in regulating the synthesis of the major excitatory transmitter in the brain. The purpose of this proposal is to study the regulation of these genes in glutamatergic neurons at the level of protein synthesis, as well as at the level of cycling between cellular compartments, in response to physiological and pathophysiological conditions, and to determine whether SAT1 and SAT2 are potential targets to modulate presynaptic glutamate synthesis and eventual exocytotic release. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POLYGLUTAMINE AGGREGATES Principal Investigator & Institution: Wetzel, Ronald B.; Professor; Medicine; University of Tennessee Knoxville Knoxville, Tn 37996 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2005 Summary: (Adapted from applicant's abstract): In the expanded CAG repeat diseases, such as Huntington's Disease, abnormally long polyglutamine sequences have been implicated as the principle causative factor of the disease. The mechanism by which these molecules promote neurodegeneration is not clear, but a large body of evidence suggests that the mechanism has something to do with the enhanced ability of lengthened polyglutamine sequences to self-associate into oligomers or aggregates. While there is an imperfect correlation of disease physiology with the appearance of large aggregates in cellular nuclei, there is also a lot of indirect evidence, such as the widely reported involvement of cellular chaperones, that a misfolding / aggregation process is involved in these diseases. One limitation in our ability to progress more deeply into the disease mechanism is our ignorance of the details of the process and products of polyglutamine aggregation. For example, improved correlation of disease development with polyglutamine aggregation might be obtained if it were possible to distinguish different sizes and types of aggregates. There is significant information on the behavior of polyglutamine sequences from cellular expression experiments, but, owing to the very poor solubility properties of these molecules, there is much less mechanistic and structural information on defined polyglutamine sequences at the in vitro chemical level. This application is based on recent advances in this laboratory in the ability to solubilize these molecules and control their aggregation in vitro. A series of chemically synthesized polyglutamine sequences of different lengths will be developed
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Glutamine
and used to pursue the following aims. The length dependence of the kinetics and thermodynamics of the aggregation process will be characterized. The length dependence of aggregate structure will also be characterized. Mutational analysis o f the polyglutamine sequence will be conducted in order to better define the unique role of glutamine in aggregation and to better understand aggregate structure at the atomic level. Finally, the abilities of a series of molecular chaperones to retard and reverse the aggregation process will be characterized in vitro. The work should lead to a better understanding of the role of polyglutamine self-association in the disease mechanism and the nature of the toxic entity in turn; this should stimulate new work on the therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POLYGLUTAMINE NEURODEGENERATION
CONFORMATION
AND
Principal Investigator & Institution: Finkbeiner, Steven M.; Assistant Professor; J. David Gladstone Institutes 365 Vermont St San Francisco, Ca 94103 Timing: Fiscal Year 2003; Project Start 15-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Huntington's disease (HD) belongs to a family of at least eight inherited, untreatable neurodegenerative diseases. Each is caused by an abnormal polyglutamine (polyQ) expansion in a different protein. In each, disease occurs when the polyQ stretch exceeds a certain length and symptom onset is inversely related to its length. Abnormal deposits of protein called inclusion bodies (IBs) characterize many of these diseases. Whether IBs are pathogenic, an epiphenomenon, or a beneficial defense response is controversial. Abnormal polyQ expansions probably cause degeneration by conferring a toxic gain of function to proteins. PolyQ expansions may adopt a conformation that is different depending on whether huntingtin (htt) is in IBs or not. We hypothesize that abnormal polyQ expansion alters the conformation of soluble mutant htt, enabling it to interact with cellular targets and produce neurodegeneration, independent of IB formation. Certain heat shock proteins (HSPs) can protect cells against polyQ and regulate IB formation. It is unknown whether they act mainly on IBs, oligomers, or malfolded monomers. It is unknown whether htt needs to oligomerize to adopt a toxic conformation and whether the length or the composition of the polyQ stretch is critical to conformation or aggregation. We have used primary neurons to develop a model of HD that recapitulates polyQ-dependent and neuronspecific death and IB formation. We have also developed monoclonal antibodies that bind a conformation of htt that correlates closely with HD symptoms and which distinguishes htt in IBs from more soluble forms. Finally, we have built a robotic microscope so we can simultaneously measure IB formation within living neurons and then track their individual fates. We propose to use these tools to accomplish the following Specific Aims: Aim 1. To determine whether the availability of a diseaseassociated conformation is a better predictor of neurodegeneration than IB formation. Aim 2. To determine whether heat shock proteins regulate htt conformation and to relate the effects of heat shock proteins on neuronal survival to the effects on conformation and on inclusion body formation. Aim 3. To determine whether htt must oligomerize or contain a contiguous stretch of pure glutamine residues to form a disease-associated conformation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PPARS AND LXR IN KERATINOCYTE DIFFERENTIATION Principal Investigator & Institution: Feingold, Kenneth R.; Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-JUL-2008 Summary: The major function of the epidermis is to provide a barrier between the external environment and the organism. To fulfill this function keratinocytes undergo a complex pathway of differentiation, culminating in keratinocyte cornification and in the formation of extracellular lipid-enriched lamellar membranes in the stratum corneum. Despite its great importance, the regulation of keratinocyte differentiation and the factors that allow for the coordinate formation of the corneocytes and extracellular lipid lamellar membranes are largely unknown. Recently it has been recognized that endogenous intracellular lipids activate PPARs and LXR. The ability of these nuclear hormones to sense cellular lipid levels, and then to regulate gene expression has led to the recognition that these receptors are "liposensors". We postulated that activation of these nuclear hormone receptor "liposensors", by the lipids generated during the formation of lamellar bodies and/or by metabolic products of these lipids, could provide a mechanism that coordinately regulates the formation of the corneocytes ("bricks") and extracellular lipid membranes ("mortar") during epidermal differentiation (Lipids->Activate Liposensors->Stimulate Expression of Proteins Required for the Cornified Envelope). As a first step in proving this hypothesis we have shown that activators of PPARs and LXR stimulate epidermal differentiation. In this proposal, we plan to focus on the molecular mechanisms by which activators of PPARs and LXR stimulate differentiation. Hypothesis: PPAR alpha, delta, gamma, and LXR activators stimulate keratinocyte differentiation by increasing the levels of AP-1 proteins, thereby stimulating the expression of a variety of key genes required for keratinocyte differentiation that contain AP-1 regulatory elements in their promoters. Aim 1. To determine if the stimulation of differentiation induced by PPAR delta and PPAR gamma activators is receptor mediated (Studies have already been completed for PPAR alpha and LXR activators during the current funding cycle). Aim 2. To determine if PPAR and LXR activation of AP-1 response elements is a general mechanism accounting for the increased expression of genes important in differentiation. Aim 3. To determine if activators of PPAR alpha, delta, gamma, and LXR increase AP-1 protein levels thereby increasing AP-1 activity and the functional importance of these increases. Aim 4. To determine the mechanism by which activation of PPARs and LXR increase AP-1 protein and mRNA levels we will localize the sites in the promoters of the AP-1 proteins that mediate the increase in expression induced by PPAR alpha, delta, gamma, and LXR activators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEINS CARRYING ONE OR MORE UNNATURAL AMINO ACIDS Principal Investigator & Institution: Rajbhandary, Uttam L.; Professor of Biochemistry; Biology; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2008 Summary: (provided by applicant): The major objective of this proposal is to develop methods for the site specific insertion of one or more amino acids analogues into proteins in eubacteria and in eukaryotes. The amino acid analogues to be used could include those that are photoactivatable, those that are fluorescent, those that carry
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Glutamine
reactive side chains such as keto and azido groups, heavy atoms such as iodine, spectroscopic probes and those that mimic phospho-amino acids. Besides providing a method for the production of proteins with novel chemical and biological properties, proteins carrying such amino acid analogues will have wide applications in biology including studies on the folding, structure, stability and function of proteins, proteinprotein interactions, protein localization and protein dynamics in vivo, crystallographic structure analyses and signal transduction. Two approaches are proposed. The first consists of the use of an amber suppressor transfer RNA (tRNA) aminoacylated in vivo with an amino acid analogue with the help of a mutant aminoacyl-tRNA synthetase, to insert the amino acid analogue at a specific site in a protein. A second, more general, approach is based on the finding in the investigator's laboratory that suppressor tRNAs, including those that are aminoacylated, can be imported into mammalian cells. This finding opens up the possibility of importing suppressor tRNAs aminoacylated in vitro with a variety of amino acid analogues for the site specific insertion of one or more amino acid analogues into proteins. The specific aims are: (1)To isolate mutants of (i) yeast tyrosyl-tRNA synthetase, which aminoacylate amber suppressor tRNA with iodotyrosine, p-trifluoromethyl-diazirinylphenylalanine or p-azido phenylalanine and (ii) E. coli glutaminyl-tRNA synthetase, which aminoacylate amber suppressor tRNA with 2-amino 5-keto hexanoic acid, an analogue of glutamine in which the side chain CH2CH2CONH2 is replaced by - CH2CH2COCH3. (2) To identify, produce and purify amber and ochre suppressor tRNAs, which are not aminoacylated by mammalian aminoacyl-tRNA synthetases and which are highly active in suppression in mammalian cells. (3) To optimize the conditions for import of suppressor tRNAs aminoacylated with amino acid analogues into mammalian cells and to use them for site specific insertion into proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF BRAIN NEUROTRANSMITTER SYNTHESIS Principal Investigator & Institution: Hutson, Susan M.; Professor; Biochemistry; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 05-JUN-2000; Project End 31-MAY-2004 Summary: Glutamate is the most widely used excitatory neurotransmitter in the nervous system. Certain diseases and neurodegenerative disorders are thought to involve disturbances of the glutamatergic systems of the brain or retina. The goal of this proposal is to understand the mechanisms that regulate glutamate levels in the nervous system. Considerable evidence indicates that glial cells rapidly internalize glutamate released by neurons during neurotransmission converting it to glutamine before releasing it back to neurons in the glutamate/glutamine cycle. However, it is now clear that possibly as much as 50 percent of the glutamate taken up by the glia is actually converted to pyruvate and lactate. Therefore, the nervous system must regenerate the lost carbon by carboxylation of pyruvate catalyzed by the anaplerotic enzyme pyruvate carboxylase (PC) which is found is astroglia. Second, it now appears that rather than ammonia the essential branched chain amino acids (BCAA) are needed to provide sufficient alpha-amino nitrogen for optimal rates of de novo glutamate synthesis. Indeed, it is our hypothesis that the BCAA and branched chain aminotransferase isoenzymes (cytosolic BCATc, mitochondrial BCATm) participate in a nitrogen shuttle whereby the glial BCATm and neuron specific BCATc act in series to transfer nitrogen from neurons to astrocytes. The aims of this proposal are designed to understand the mechanisms that regulate glutamate levels in the nervous system and test the BCAA shuttle hypothesis. 1) We will develop methods to simultaneously measure the rate of
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de novo glutamate synthesis and the rate of glutamate glutamine cyclin in the ex vivo retina and in brain in vivo and correlate the influence of neuronal activity with flux. Both H14CO3 and 13C NMR spectroscopy will be used in vivo for the kinetic analysis. 2) The function of the BCAT isoenzymes in regulating glutamate synthesis and brain neurotransmitter pool sizes will be quantified in vivo in brain and ex vivo in the retina. The hypothesis that the neuroactive drug gabapentin acts via specific inhibition of cytosolic BCATc will be tested. 3) The degree of control exerted by the anaplerotic enzyme pyruvate carboxylase (PC) relative to that of the BCAT isoenzymes will be assessed. Antisense technology will be used to vary enzyme levels in vivo. Data will be analyzed using control strength theory to determine the relative control strength of the BCAT and PC on the pathways of de novo glutamate synthesis. Finally, understanding the mechanisms that regulate glutamate synthesis will increase our knowledge of certain disease processes and may allow for future generation of novel therapeutic compounds. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF GLUTATHIONE SYNTHESIS IN OXIDATIVE STRESS Principal Investigator & Institution: Forman, Henry J.; Professor; Environmental Health Sciences; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 15-APR-1996; Project End 31-MAR-2005 Summary: (Adapted from the Investigators abstract). This proposal focuses on the signal transduction mechanisms regulating the increase in de novo glutathione (GSH) synthesis that occurs during adaptation to oxidants and other electrophiles. GammaGlutamylcysteine synthetase (GCS), the rate limiting enzyme in de novo GSH synthesis, is composed of two subunits. Both GCS genes are transcriptionally up-regulated in response to stress from oxidants and electrophilic xenobiotics. Nonetheless, a mismatch between expression of the two GCS subunit proteins may result in altered kinetics and/or decreased stability of the enzyme. gamma-Glutamyl transpeptidase (GGT) is an exoenzyme that provides substrates for GSH synthesis by breaking down extracellular GSH. GGT enzymatic activity and mRNA transcription also increases in response to oxidants. While much has been learned over the past few years regarding mechanisms of GSH increases in adaptation, the signaling mechanisms that govern regulation of GCS and GGT on the transcriptional, post-transcriptional and post-translational levels remain largely unresolved. The investigators propose to test the following hypotheses in three aims: 1- that signaling for the transcriptional activation of GCS genes by electrophiles and H2O2-generating compounds occurs through overlapping pathways; 2- that the GCS regulatory subunit (GCS-LS) stabilizes the catalytic subunit against proteolysis as well as regulates the kinetics; 3- that GGT transcription by reactive oxygen species is mediated through activation specific signaling pathways and cis acting element(s) activated by H2O2. These hypotheses will be tested using the agents (2,3dimethoxy-1,4-naphthoquinone (DMNQ), 4-hydroxynonenal (4HNE), and betanaphthoflavone (BNF)) at concentrations and incubation times that cause increased transcription of both GCS subunits. Methods to be used include, dominant negative and constitutively active signaling components, kinase assays, in vivo footprinting, reporter construct, tetracycline regulated antisense transfection, and measurement of reactive oxygen species, glutathione oxidation and alpha-unsaturated aldehydes. These aims will be carried out by using established cell models modified as needed to determine whether the conclusions are unique or generally applicable. The long-range goal of their
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research is an understanding of the regulation of GSH synthesis and the potential for its pharmacological manipulation to enhance synthesis of this essential cellular constituent. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF THE DEVELOPMENT OF TRYPANOSOMA BRUCEI Principal Investigator & Institution: Wang, C C.; Professor; Pharmaceutical Chemistry; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2004; Project Start 01-DEC-1984; Project End 31-JAN-2009 Summary: (provided by applicant): African trypanosomes are parasitic protozoa and causative pathogens of sleeping sickness in humans and nagana in cattle. They are deeply branched primitive eukaryotes with many simple and unique biological features to make interesting models for basic studies and provide opportunities for chemotherapeutic control of the diseases they cause. The 26S proteasome in Trypanosoma brucei exists in a single species and performs many vital functions including cell cycle regulation. Its substrate specificity differs from that of the human proteasome, which allows specific inhibitor design. Insect form T. brucei has also a very simple cyclin-mediated cell cycle control involving only one essential G1 cyclin and one mitotic cyclin resulting in a leaky checkpoint regulation. There are four specific aims in our proposal; (1) to analyze the activity profiles of individual catalytic subunits in the T. brucei proteasome and compare them with those of the human proteasome. A P1glutamine tetrapeptide has been identified as a preferred substrate by the T. brucei proteasome. Further selective substrate and inhibitor design will be pursued with the increasing understanding of proteasome activity profiles; (2) to crystallize the 19S regulatory complex of T. brucei proteasome for structural analysis. The complex has an extraordinary stability and could become the first to have its structure resolved; (3) to analyze the G2/M checkpoint regulation in the bloodstream and insect forms of T. brucei. A regulatory complex most likely consisting of the mitotic cyclin, cyclindependent protein kinase, anaphase promoting complex (E3), an E2 and the proteasome will be identified and analyzed by the tandem affinity purification system and yeast two-hybrid screen and the functions of individual subunits characterized by RNA interference analysis; (4) to analyze and compare the two different mechanisms of G1/S checkpoint control in the bloodstream and insect forms of T. brucei and identify the two distinctive regulatory complexes by similar experimental approaches as stated above. The two forms of T. brucei share a similar G2/M control but distinctive G1/S regulations. A potential shift from one machinery of G1/S control to another during the differentiation from bloodstream into the insect form will be closely monitored and the triggering factor for this shift will be pursued. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RETINOIC BINDING/TRANSGLUTAMINASE
ACID-ACTIVATED
GTP-
Principal Investigator & Institution: Cerione, Richard A.; Professor; Molecular Medicine; Cornell University Ithaca Office of Sponsored Programs Ithaca, Ny 14853 Timing: Fiscal Year 2002; Project Start 01-JUN-2000; Project End 31-MAY-2004 Summary: Tissue transglutaminases (TGases) are GTP-binding/GTPases with an enzymatic (transamidation) activity that catalyzes the covalent linkage between glutamine residues and primary amino groups, resulting in the formation on new protein-protein and protein- polyamine complexes. The TGases have been implicated in
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a number of important biological responses including neuronal development and degeneration, as well as retinoic acid-induced cellular differentiation, and apoptosis. Both the GTP-binding and transamidation activities of the TGases are activated by retinoic acid. Recently, we identified two candidate target/binding partners for the TGase, namely, the eukaryotic initiation factor (eIF)5A, and the retinoblastoma gene product (Rb), both of which are essential for cell viability. We also have found that the TGase-catalyzed transamidation of Rb protects it against proteolytic degradation by caspases. The studies outlined in this application are aimed at understanding different aspects of the structure and function of this interesting dual function GTP- binding protein/transamidase and its role in retinoic acid- induced cellular differentiation. There are three specific aims. 1.) Delineate the mechanistic basis for the intramolecular coupling between the GTP-binding and transamidation activities of the TGase. We plan to determine how the TGase is able to bind and hydrolyze GTP and to establish how the GTP-binding/GTP hydrolytic cycle regulates the transamidation activity. The ultimate aim will be to generate TGase mutants that are defective in GTP-binding or that contain GTP-binding/GTP hydrolytic activity that is uncoupled from transamidation activity, since these mutants should be useful for cellular studies of TGase function. 2.) Determine how retinoic acid mediates the cellular regulation of the TGase. In these studies, we plan to determine whether a negative regulatory protein is responsible for maintaining the TGase in an inactive state in the absence or retinoic acid treatment, as well as begin to establish the molecular signals responsible for the retinoic acidstimulated activation of the TGase. 3.) Establish a role for the interactions of the TGase with two new target/binding partners that are essential for cell growth. The main emphasis of these studies will be to determine whether the retinoic acid-dependent interactions of the TGase with Rb and eIF-5A are essential for ensuring cell viability when cells undergo cell-cycle arrest during differentiation. The results of these studies should yield new information regarding the regulation of an important dual function GTP-binding protein/transamidase and its role in mediating the balance between cellular differentiation and apoptosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RIBOZYMES FOR THE EVOLUTION OF THE GENETIC CODE Principal Investigator & Institution: Suga, Hiroaki; Associate Professor; Chemistry; State University of New York at Buffalo Suite 211 Ub Commons Amherst, Ny 14228 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: The contemporary aminoacyl-tRNA synthetases (aaRSs) are highly specific toward cognitive amino acids and tRNAs, because the fidelity of translation from genetic code to proteins relies mainly upon the accurate aminoacylation of tRNAs. Consequently, the mechanism of their recognition events is extremely complex, which has made it difficult to engineer the aaRSs with desired specificities. The central goal of this proposal is to devise a novel and practical catalytic system composed of catalytic RNA molecules (ribozymes) for the synthesis of natural and non-natural aminoacyltRNAs. We have recently succeeded in generating a novel ribozyme capable of synthesizing aminoacyl-tRNA. This ribozyme, referred to as ARS ribozyme (aminoacyltRNA synthetase ribozyme), is able to specifically recognize a glutamine cyanomethyl ester and charge the glutaminyl group on a tRNA molecule. In this proposal, we will plan to systematically evolve the ARS ribozyme into highly selective and efficient ARS ribozymes for the synthesis of various aminoacyl-tRNAs. Our ribozyme-based catalytic system will potentially offer a simple and facile method for the synthesis of aminoacyltRNAs in vitro. The results from these experiments will be used to drive future direction
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Glutamine
of our long-term goal, a cell-free in vitro translation system composed of ARS ribozymes, which facilitates the site-specific incorporation of non-natural amino acids into proteins. Our experiments may also provide new evidence to support an RNAbased translation system postulated in the context of the RNA world hypothesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF HUNTINGTIN IN VESICLE TRANSPORT Principal Investigator & Institution: Difiglia, Marian; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-AUG-1998; Project End 31-JUL-2006 Summary: (provided by applicant): A polygutamine expansion in the N-terminus of huntingtin (N-hn) causes Huntington's disease (HD). There is no effective treatment for HD. Although mutant N-Fin fragments are known to accumulate in HD neurons and cause cell dysfunction in vitro, a mechanism (or mechanisms) that explains the selective loss of striatal and cortical projection neurons remains elusive. Wild type and mutant htt associate with membranes in the endocytic and secretory pathway. Our overall hypothesis is that mutant N-htt 's association with neuronal membranes contributes to early cellular dysfunction in the cytoplasm in HD. One of these membrane compartments includes the autophagosome/lysosomal system, which accumulates fulllength or large N-htt fragments of mutant htt. Although htt ostensibly lacks transmembrane domains, it associates tightly with membranes. We speculate that candidate domains in the N-terminus involved in protein-protein interactions promote membrane binding. Little is known about the degradative pathways that form N-htt fragments in vivo. Identifying the sites of protease cleavage in the N-terminus of htt is important for understanding how the protein is regulated. Calpain, a calcium dependent protease, which regulates the function of many proteins involved in membrane/cytoskeleton organization, cleaves htt near its N-terminus and produces long-lived N-htt fragments that are enriched in membrane fractions in brain. We speculate that mutant N-htt products of calpain cleavage undergo a different processing from the wt fragments in neurons that leads to cellular dysfunction in HD. HD mice also show abnormal function of striatal NMDA receptors. One way that mutant Fin might cause the dysfunction of NMDA receptors is by disrupting the assembly of NMDA receptor subtypes at the cell surface. The specific aims are: 1: To understand the role of mutant htt induced autophagy in cell dysfunction, 2: To determine whether htt proteolysis by calpain contributes to HD pathogenesis and 3: To determine the effects of mutant htt on protein transport within the secretory pathway. The results of these studies will provide new insights about the mechanisms of cellular dysfunction in HD and suggest novel therapeutic targets that can reduce the potentially harmful effects of mutant N-htt fragments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE OF PROTEIN PHOSPHATASES IN INSULIN SECRETION Principal Investigator & Institution: Kowluru, Anjaneyulu; Associate Professor; Pharmaceutical Sciences; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (From applicant's abstract) While a majority of extant studies have focused since on the protein kinases, very little is known of the regulation and roles of protein phosphatases (PPases) in physiologic insulin secretion from the pancreatic beta cell. The catalytic activity of certain enzymes of intermediary metabolism is influenced by their
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phosphorylation status. For example, acetyl CoA carboxylase (ACC), a lipogenic enzyme, is modulated by phosphorylation (inactive)- dephosphorylation (active). Here in the investigators describe a novel cytosolic, okadaic acid-sensitive (PP2A-like) PPase that dephosphorylates and activates ACC in the beta cell. Activity of this PPase is augmented by methylation at its C-terminal leucine. Further, the methylated form is converted to its inactive, demethylated form by a cytosolic serine esterease-like enzyme, also localize in the beta cell. Physiologic concentrations of glutamate and magnesium stimulate the carboxyl methylation as well as the catalytic activity of this PPase and concomitantly increase ACC activity. Effects of glutamate and magnesium are specific for ACC-phosphatase, but not ACC-kinase. Insulinotropic concentrations of glucose or glutamine stimulate the carboxyl methylation of this PPase in intact beta cells. More importantly, activity of this ACC-PPase is abolished in islet derived from the GK rat, a model for NIDDM, compared to islets from the control Wistar rats. Using isolated rat islets and pure beta (HIT-T15 and INS-1) cells, the investigators propose to study the regulation of this PPase, and thereby ACC, at 3 cellular levels (i.e. subcellular fractions, intact islets, and purified proteins in reconstituted systems). The investigators will also purify this PPase using microcystin -sepharose affinity columns to determine changes in the (A, B and C) subunit composition of PP2A under various experimental conditions, to establish a link between the carboxyl methylation of the C-subunit and the assembly of PP2A haloenzyme. The investigators will characterize the methylating and demethylating enzymes of PP2 Ac and study the interaction of ACC with its putative PPase. Using similar approaches, the investigators will examine the abnormalities in ACC-phosphatase in the diabetic GK islet and investigate if such a defect is reversed by treatment of diabetic rats with insulin or phlorizin. The proposed studies should establish a link between ACC activation and physiologic insulin secretion from isolated beta cells. These studies will also identify the locus that is causal to the observed defect in ACC-phosphatase and ACC activation signaling cascade in the diabetic beta cell, leading to abnormal insulin secretion demonstrable in this model for NIDDM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SALIVARY PROTEINS IN DENTAL INTEGUMENTS Principal Investigator & Institution: Oppenheim, Frank G.; Professor and Chair; Periodontology & Oral Biology; Boston University Medical Campus 715 Albany St, 560 Boston, Ma 02118 Timing: Fiscal Year 2002; Project Start 01-JAN-1983; Project End 31-MAY-2005 Summary: The acquired enamel pellicle is a protein film readily formed on tooth mineral surfaces in the oral environment. It has been established that its formation is driven by the adsorption of proteins and peptides derived from oral fluid. Most of these proteins originate from either parotid or submandibular/ sublingual secretions which undergo modifications in the oral cavity before or after adsorption to the hydroxyapatite crystallites of tooth enamel. The composition and the structure of this acquired enamel pellicle are still largely unknown but play functionally a vital role with important physiological/clinical implications. A major thrust of this application is to use state-ofthe-art proteomics to identify and characterize the major components of the in-vivo formed pellicle. Since the pellicle has an inner aspect facing the tooth surface and an outer aspect connected to the bacterial biofilm known as Dental plaque the functions of pellicle are multifaceted and complex. Another major goal is to investigate the protective functions of the pellicle vis-a-vis the maintenance of the mineral phase of enamel and the interplay between molecular entities of the pellicle and those bacteria which constitute the early colonizers of the biofilm forming on the tooth surface. The nature of
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the pellicle with respect to the early attachment of bacteria including those which are known periodontal pathogens will be studied in vitro and in vivo. The Specific Aims of the project are to: 1) Characterize components from pellicles formed in vivo by a variety of isolation techniques including 2D-electrophoresis followed by proteomic analyses comprising MALDI-TOF MS. LC-ESI MS and LC-MS/MS; 2) Explore the protective functions of the enamel pellicle by determining the affinity of its components to hydroxyapatite, the inhibitory potential of pellicle proteins/peptides of calcium phosphate precipitation from supersaturated solutions, and the capacity to retard demineralization; 3) Determine in vitro binding parameters of individual early pellicle colonizers, assess the role of transglutaminase in pellicle-bacterial interactions and employ biomimetic approaches to modify functional aspects of pellicle components; 4) Investigate with the checkerboard DNA-DNA hybridization assay the in vivo binding of early pellicle colonizers in healthy individuals and gingivitis patients, assess the relative role of exocrine and serum derived proteins/peptides on pellicle colonization in vivo and explore effects of different local environments in the oral cavity on these processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SCORE PROGRAM AT NEW MEXICO STATE UNIVERSITY, LAS CRUCES Principal Investigator & Institution: Kuehn, Glenn D.; Professor of Biochemistry; Chemistry and Biochemistry; New Mexico State University Las Cruces Las Cruces, Nm 880038001 Timing: Fiscal Year 2002; Project Start 09-SEP-1991; Project End 31-MAY-2004 Summary: This is an application for a new SCORE Program at New Mexico State University (NMSU) at Las Cruces. A goal of NMSU is to expand research is at the institution for participation by ethnic minority students who desire to pursue careers in the biomedical science disciplines. The proposed SCORE Program has its goals: (i) To significantly improve the capabilities of NMSU to conduct biomedically relevant research by increasing the numbers of faculty who conduct biomedical research, increasing the inventory of specialized single-user research instrumentation, and improving the capacity to maintain research instrumentation; (ii) To significantly improve the quantity and quality of biomedical research conducted at NMSU by broadening grantsmanship efforts of faculty participants and increasing the numbers and quality of research publications; (iii) To integrate the activities of the SCORE Program with an anticipated RISE Program to maximize resources for training minority scientists in the biomedical sciences by engaging students in SCORE Program research projects; (iv) To increase the capacity of NMSU to self-evaluate, assess, and monitor its multi- component research programs by engaging trained personnel in the SCORE Program's evaluation plan and subjecting the Program to annual review by an external evaluation committee. This application contains research proposals for nineteen research subprojects and three pilot subprojects. Disciplines represented among these proposals include Agronomy, Animal Science, Anthropology, Biochemistry, Biology, Chemistry, Chemical Engineering, Molecular Biology, Microbiology and Psychology. The research topics of proposed projects include methods for radiolabeling medical diagnostic reagents with technetium and rhenium, avian cardiovascular adaptations, the bacterial proteosome, glycosylation processes in CHO cells, apoptosis, acid tolerance of E. coli O157:h7, metabolic engineering of secondary metabolism, evolution of RNA viruses, cytosolic and chloroplastic glutamine synthase, biological dechlorination reactions, mechanisms of environmental stress resistance, toxicokinetics of swainonine, neuromodulation of growth hormone, maternal/infant synchrony in cortisol and
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behavior development, embryonic control of blood pressure, modification of clays for resolving racemic mixtures, gene expressions during inner ear development, and chemical synthesis of cation chelators, steroids and etoposide derivatives, and boronated biomolecules. This SCORE Program will continue a 24-year old MBRS Program which has advanced 280 minority students (83% of participants) on to post baccalaureate programs and produced 52 minority Ph.D. recipients since 1974. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SECRETIN AND GASTRIC MOTILITY Principal Investigator & Institution: Owyang, Chung; Chief, Division of Gastroenterology; Internal Medicine; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUN-1990; Project End 31-MAR-2005 Summary: Duodenal acidification inhibits gastric antral contractions, promotes gastric fundic relaxation, and thereby protects the duodenum from excess acid exposure. Secretin plays an important role in this process, mediating duodenal acid-induced gastric relaxation by acting on vagal afferent neurons that activate vagal motor neurons, releasing VIP which then evokes gastric relaxation by way of prostaglandin pathways. The current proposal focuses on vagovagal circuits that are activated by secretin and duodenal acid. It is postulated that secretin activates vagal afferent fibers that release CGRP that then stimulates interneurons in the nucleus tractus solitarius. GABAergic neurons inhibit dorsal motor nucleus of the vagal cholinergic neurons which synapse with intragastric cholinergic neurons, while stimulation of glutaminergic neurons activate dorsal motor nucleus vagal neurons which synapse with intragastric VIP neurons. This provides a mechanism whereby single vagal afferents may concurrently excite and inhibit vagal efferent transmission producing dysfacilitation of cholinergic and activation of nonadrenergic and noncholinergic input to the stomach to optimize gastric relaxation. In the current proposal, the neurotransmitter coding utilized by vagal fibers possessing secretin receptors will be assessed by intracellular recording and labeling techniques. The intracellular mechanisms involved in secretin-stimulated release of CGRP from the nodose ganglia will be explored. Both morphologic and electrophysiologic characterization of duodenal acid and secretin-stimulated nucleus tractus solitarius neurons will be performed and their neurochemical phenotypes examined. In vivo, the secretin-induced release of glutamine and GABA will be quantified using radionucleotide tagging techniques. Finally, the dorsal motor neuron vagoneural circuits mediating the action of secretin and the roles of GABA and NMDA will be explored. This should provide a comprehensive characterization of the neural components of the vagovagal circuit activated by secretin to effect gastric relaxation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNALING CASCADES, ALLOSTERY AND THE PYRIMIDINE PATHWAY Principal Investigator & Institution: Guy, Hedeel I.; Biochem and Molecular Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: In mammalian cells, the rate of de novo pyrimidine biosynthesis is regulated by the multi-functional protein CAD. The protein, which catalyzes the first half of the pathway, consists of six copies of a 243 kDa polypeptide folded into separate structural domains that carry glutamine dependent carbamoyl phosphate synthetase (CPSase),
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aspartate transcarbomoylase (ATCase) and dihydrooortase (DHOase) activities. The activity of the pathway is precisely controlled and increases when cells are induced to proliferate. Studies of the purified protein have shown that CPSase, which catalyzes the initial, rate limiting step in the pathway is the major locus of regulation and is allosterically controlled by UTP, an inhibitor and PRPP, an activator. In addition, the activity of the complex is regulated by protein kinase A mediated phosphorylation, although its role in regulating the growth state and cell cycle changes in the activity of the pyrimidine biosynthetic pathway is not at all clear. The recent discovery that EGF stimulation results in MAP kinase mediated phosphorylation and activation of CAD makes its possible to resolve this ambiguity. The objective of this research is to decipher the interrelationships and assess the importance of all these control mechanisms on the regulation of pyrimidine biosynthesis in vivo. The rate of de no pyrimidine biosynthesis, the size of the allosteric effector pools and the phosphorylation state of the protein will be examined in mammalian cells grown in culture and in transfectants that express CAD mutants in which one or more of the regulatory mechanisms have been disabled. The approach will be to extrapolate the extensive information developed on the regulation of purified CAD to develop a comprehensive model that can account for the in vivo regulation of de novo pyrimidine biosynthesis in different growth states, phases of the cycle and in cells stimulated by growth factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SIGNIFICANCE OF GGT EXPRESSION IN TUMORS Principal Investigator & Institution: Hanigan, Marie H.; Associate Professor; Cell Biology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2002; Project Start 01-AUG-1992; Project End 31-MAR-2004 Summary: (adapted verbatim from the investigator's abstract) Cisplatin is the most effective chemotherapy drug for the treatment of ovarian cancer. Its usefulness in the clinic is restricted by dose-limiting nephrotoxicity and the development of drugresistance within the tumor. During the previous funding period our studies demonstrated that the nephrotoxicity of cisplatin is due to the metabolism of cisplatinglutathione conjugate through a GGT- mediated pathway in the kidney. We further demonstrated that this GGT-mediated toxicity is specific to the kidney. When GGT was transfected into tumor cells it reduced the toxicity of cisplatin rather than increasing it as was seen in the kidney. These findings indicate that there are two distinct mechanisms of cisplatin toxicity. The delineation of these two mechanisms would provide the opportunity to inhibit the side effects of cisplatin without compromising its antitumor activity. The current proposal focuses on defining the mechanisms by which cisplatin exerts its toxic effects and identifying the mechanism by which tumor cells develop resistance to cisplatin. The first specific aim is to further characterize the unstable cisplatin-glutathione conjugate that is a substrate for GGT and follow its metabolism within the kidney. A series of cisplatin-glutathione conjugates will be tested as substrates for GGT-mediated activation to nephrotoxins by LLC-PK1 cells and human renal proximal tubule cells. Cisplatin-glutathione conjugates will be isolated by HPLC and their structure determined by Mass Spectrometry. The pathway by which they are metabolized will be determined with the use of selective inhibitors of enzymes within the pathways. Inhibitors that block the activation of cisplatin in vitro will be tested for their ability to block the nephrotoxicity of cisplatin in vivo. The second specific aim is to identify the mechanism by which tumors become resistant to cisplatin in vivo. Human epithelial ovarian tumors will be propagated in nude mice. Half the mice will be treated
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with cisplatin. Cisplatin resistant tumors will be isolated after several courses of treatment. mRNA will be isolated from these tumors and differentially expressed genes will be isolated by representational differential analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SKELETAL MUSCLE NUTRIENT SENSING Principal Investigator & Institution: Obici, Silvana; Medicine; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Obesity occurs when caloric intake exceeds expenditure. The increasing prevalence of obesity in industrialized societies has generated new interest in the mechanisms underlying the control of energy balance. In humans, reduced rate of energy expenditure, which is largely accounted for by oxidative phosphorylation in skeletal muscle, is a risk factor for future weight gain. Nutrients, via the activation of nutrient-sensing pathways, activate adipostatic responses (e.g. leptin) that attempt to limit lipid storage by enhancing energy expenditure and inhibiting food intake. A major nutrient-sensing pathway, the hexosamine biosynthetic pathway (HBP) has been recently shown to increase local leptin expression in skeletal muscle. Yet, acute pharmacological activation of HBP induces a dramatic drop in skeletal muscle energy production, by downregulating the expression of genes for oxidative phosphorylation. Based on these observations, we wish to develop animal models designed to define how the physiological regulation of HBP modulates energy homeostasis. In particular, we will use transgenic animal models to discern the metabolic consequences of activation of HBP in muscle from those derived from the associated local induction of leptin. We will generate transgenic mice lines carrying constitutive and moderate elevations of the enzyme glutamine:fructose 6P amidotransferase (GFAT, which catalyzes the first committed step of HBP and regulates the flux through this pathway), or of leptin in skeletal muscle. The careful phenotyping of these animal models should allow one to define the direct and respective roles of muscle HBP and leptin in the regulation of energy expenditure and substrate oxidation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SLEEP MECHANISMS IN CHILDREN: ROLE OF METABOLISM Principal Investigator & Institution: Haddad, Gabriel G.; Pediatrics; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 23-SEP-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Sleep and the neurobiological mechanisms controlling sleep/wakefulness have been an enigma in spite of important recent advances in the field. Although it is well known now that sleep affects a variety of systems, including the cardio-respiratory, endocrine and autonomic systems, we still do not understand why we sleep and the mechanisms that control sleep. For example, we do not have a good understanding of the mechanisms that induce or maintain sleep or those mechanisms that are activated with sleep deprivation. One of the potentially important areas that have started to develop is the role of brain metabolism in sleep. Although metabolic studies during sleep have been done in the past few decades, new developments in brain imaging and spectroscopy have made it possible only recently to examine the importance of metabolism in sleep research. Furthermore, and of major interest, is the growing evidence that glia play a critical role in maintaining neuronal
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function through metabolic support through glutamate re-cycling and possibly by providing neurons with substrates for glucose oxidation. Glycogen is found only in glia and hence glycogen metabolism, the glutamine-glutamate cycling and glucose oxidation involve links between glia and neurons. Hence, in order to understand sleep and its mechanisms, it becomes important to study the functional integrity and coupling of neurons and glia and their relationship as a function of state. For conceptual reasons and in order not to complicate the experimental matrix, we will focus this application on stage III-IV sleep and will address our questions comparing this sleep stage to a well defined state of wakefulness. Furthermore, since previous studies have taught us about sleep and its mechanisms by studying sleep deprivation, we will, in a subset of our children, address the same questions after sleep deprivation. Our specific hypotheses are as follows: 1. Stage IV sleep has a lower metabolic requirement and a lower glutamate turnover rate (tricarboxylic acid cycle rate) in both neurons and glia, as compared to wakefulness. 2. As compared to wakefulness, sleep stage IV is characterized by a lower rate of brain neuronal glutamate release and glial glutamate uptake in children; this reduced glutamate/glutamine cycling during this sleep stage in brain of children is prevented by sleep deprivation. 3. Brain glycogen content increases during the course of sleep in children and sleep deprivation markedly lowers glycogen content. Our long term aims are a) to better understand sleep and b) to be able to better understand diseases that afflict children or adult and which impact on their sleep or diseases that are sleep-related that impact on other functions including neurocognitive, cardiovascular or behavioral functions. As seen from reviewing the state-of-the-art above, there are major gaps in our knowledge and this application focuses on a number of these gaps. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPECIFICITY IN CLASS I AMINOACYL-TRNA SYNTHETASIS Principal Investigator & Institution: Perona, John J.; Associate Professor; Chemistry and Biochemistry; University of California Santa Barbara 3227 Cheadle Hall Santa Barbara, Ca 93106 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2005 Summary: (provided by applicant): A multidasciplinary study aimed at uncovering the structural and energetic basis for amino acid and transfer RNA specificity in several class I aminoacyl-tRNA synthetases is proposed. The experimental plan will focus on the structure-based design of directed modifications in both the synthetase and tRNA, and on the insightful analysis of modified complexes by a variety of enzymological and biophysical methods. The role of the globular tertiary core region of glutamine-specific tRNA in aminoacylation will be explored by exploiting the availability of an extensive tRNA sequence database, as well as by the introduction of highly specific chemical modifications to the sugar-phosphate backbone. Glutaminylation kinetics, together with high-resolution structures bound to synthetase and to Ef-Tu, will be determined to assess the effects of the alterations. In a separate line of experiments, rational structurebased approaches are planned to re-engineer the amino acid specificity from glutamine to glutamate. New methodologies will be applied to improve the chemical and enzymatic synthesis of multimilligram quantities of homogeneous RNAs, and to better characterize the aminoacylation reaction by implementing a new assay useful for both steady-state and transient kinetic measurements. With improved kinetic methods in hand, a functional analysis of glutaminyl-tRNA synthetase will be pursued with the aim of addressing the kinetic basis for the amino acid specificity, the function of divalent metal ions, and the requirement for tRNA to carry out activation of the amino acid.
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These approaches will also be used to examine kinetic properties of the homologous cysteinyl-tRNA synthetase. Detailed information on the origins of class I bacterial tRNA synthetase specificities will aid drug-design approaches which exploit the structural differences between bacterial and human synthetases to develop antimicrobial agents. Re-engineering of the amino acid specificities of tRNA synthetases is also the most challenging step in the in viva production of proteins containing non-natural amino acids. Because of the broad applicability of this technology, the development of new synthetases based on the class I active site domain has potential for impact on biomedical research toward therapies for many human diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEINS
STRUCTURE
FUNCTION
OF
THE
MAMMALIAN
STRESS
Principal Investigator & Institution: Welch, William J.; Professor; Surgery; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-APR-1992; Project End 31-MAR-2005 Summary: (Applicant's abstract): Analysis of the structure and function of heat shock proteins has led to new insights regarding the pathway of protein maturation. Heat shock proteins, in their role as "molecular chaperones," participate in the synthesis, folding and intracellular transport of many, if not all, polypeptides. Increases in the levels of the heat shock proteins, as occurs in cells experiencing different types of metabolic stress, aid in the renaturation of cellular proteins adversely affected by the stress event and facilitate the synthesis and folding of new proteins needed to replace those which have been irreparably damaged. Herein Dr. Welch will continue to examine structure/function of the heat shock proteins. In first aim the identity and role of molecular chaperones interacting with nascent polypeptides still bound to the ribosome will be pursued. Here the idea that two heat shock proteins, hsp70 and hsp90, together constitute a nascent chain binding complex will be examined. Interaction of this putative nascent chain binding complex with nascent chains is suggested to help stabilize maturing polypeptides, preventing inappropriate intra- or inter-molecular interactions that might lead to misfolding and aggregation. Studies described in aim 2 will serve to complement those in aim 1 by focusing on the maturation of one particular polypeptide, the androgen receptor (AR). The rationale for studying AR biogenesis is 3-fold. First, the biological activities of the mature form of AR are known to require the help of different molecular chaperones. Second, assays to study the proper folding of AR are readily available. Finally and most importantly, mutations in AR are the basis of a neurodegenerative disease. Here expansions of a CAG repeat within the gene encoding AR result in an AR protein containing an unusually long run of glutamine residues. As a result, mutant AR readily forms nuclear and cytoplasmic aggregates which over time lead to cell demise. Thus, in aim 2 Dr. Welch will compare and contrast the maturation pathway of wild type and mutant AR and determine the role served by different molecular chaperones. In parallel, studies described in aim 3 will focus on the cellular impact of mutant AR expression. He proposes that the accumulation of mutant ARaggregates leads to the sequestration of molecular chaperones and the eventual development of chronic cellular stress. Exactly what metabolic pathways are adversely affected in the cell experiencing chronic stress will be addressed. Finally, in aim 4 we will continue with the identification and characterization of small molecules that are effective in reducing or preventing abnormal protein folding. The principal investigator anticipates that these studies, in sum, will continue to provide new insights regarding
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the structure/function of the heat shock proteins and their potential role in human diseases involving abnormal protein folding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURES AND MECHANISMS OF GLUTAMINE DEPENDENT ENZYMES Principal Investigator & Institution: Davisson, Vincent J.; Professor; Medicinal Chem/Molecular Pharm; Purdue University West Lafayette West Lafayette, in 479072040 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2007 Summary: (provided by applicant): Scientific Focus The long-term goals of this project are to establish a molecular basis for the interdomain communication in glutamine amidotransferases that relates their dynamic properties to the control of their catalytic efficiencies. This investigation aims to delineate the major mechanistic and structural aspects of two enzymes, imidazole glycerol phosphate synthase (IGPS), and guanosine monophosphate synthetase (GMPS), which catalyze the transfer of ammonia from glutamine to a purine nucleotide acceptor substrate. The general hypothesis under consideration for the glutamine amidotransferase sub-family is that the functional link between the two active sites involves the transduction of binding and chemical energy from the acceptor active site to the glutaminase site. Furthermore, the glutamine substrate specificity and catalytic efficiency is controlled by dynamic protein-protein interactions that modulate a molecular tunnel for ammonia transfer. The proposed studies will focus upon structural and mechanistic information to define the domain interactions that control the timing of the nucleotide substrate activation and glutarnine hydrolysis steps. Significance of objectives Because of the unique chemical features present in the metabolic pathway under investigation, and the detailed comparative structural information that will emerge, this project has the potential to impact the discovery and development of new therapeutic agents. In addition, these enzymes represent important examples of convergent evolution that hold many mechanistic details of how proteins transmit specific chemical information over large distances. Overall, the combination of biochemical and biophysical approaches proposed will: a) contribute to a comprehensive knowledge regarding nitrogen metabolism and b) provide critical information for the design of new selective agents of potential pharmacological importance that target essential enzymes in ammonia metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE ENCEPHALOPATHY
PERMEABILITY
TRANSITION
IN
HEPATIC
Principal Investigator & Institution: Norenberg, Michael D.; Professor; Pathology; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): Hepatic encephalopathy (HE) is an important cause of morbidity and mortality in patients with severe liver failure. Acute HE associated with fulminant hepatic failure has an extremely poor prognosis and specific therapy is not available, short of an emergency liver transplantation. Although its pathogenesis remains poorly understood, ammonia is strongly implicated as a neurotoxin, and astrocytes appear to be the primary target of ammonia neurotoxicity. Additionally, altered bioenergetics and oxidative stress are thought to play a major role in this disorder. These facts led to a consideration of the involvement of mitochondrial
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permeability transition (MPT) as a factor in the pathogenesis of HE and ammonia neurotoxicity. The MPT is a Ca2+-dependent, cyclosporin A (CsA)-sensitive process due to the opening of a pore in the inner mitochondrial membrane leading to a collapse of ionic gradients and ultimately to mitochondrial dysfunction. We have recently shown that ammonia induced the MPT in cultured astrocytes. We intend to examine the role of the MPT in HE and hyperammonemia using ammonia-treated neural cell cultures and in vivo models of HE/hyperammonemia (HA). Our working hypothesis is that ammonia induces the MPT in astrocytes, culminating in mitochondrial failure and astroglial dysfunction. A corollary of this concept is that inhibition or interference in the development of the MPT in astrocytes may ameliorate CNS dysfunction in HE. The Specific Aims of this proposal are: 1) To identify the factors responsible for the ammonia-induced MPT in cultured neural cells. Our focus will be on agents implicated in the pathogenesis of HE/H that have also been shown to induce the MPT in other cells. Specifically, we will examine the role of Ca 2+, reactive oxygen species, nitric oxide, pH and glutamine. We will determine whether these factors are elevated in ammonia-treated cultures, and whether diminishing their production or blocking their actions reduces or abolishes the MPT. Additionally, we will examine possible sequential interrelationships among these factors. 2) To determine whether ammonia-induced abnormalities in astrocytes (morphological alterations, defects in neurotransmitter uptake, and cell swelling) are mediated by the MPT, we will investigate whether inhibitors of the MPT (CsA, bongkrekik acid) are capable of diminishing or blocking the deleterious effects of ammonia. 3) To investigate the involvement of mitochondrial dysfunction as a potential factor in MPT-mediated cell injury. We will determine the state of mitochondrial function after ammonia treatment, and then investigate whether improving energy metabolism will inhibit ammonia-induced cellular injury. 4) To clarify whether the MPT occurs in in vivo models of HE (thioacetarnide treatment) and hyperammonemia. We will also determine whether factors that inhibit the MPT in vitro (e.g., CsA, trifluoperazine) are also capable of doing so in vivo. Additionally, we will assess the ability of MPT blockers to improve the clinical, histopathologic, neurochemical abnormalities, and the extent of brain swelling observed in HE/HA. We believe that these studies will yield critical data bearing on the pathogenesis of HE, and may potentially aid in the development of novel therapeutic strategies for the treatment of this condition. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TISSUE TRANSGLUTAMINASE: A ROLE IN HUNTINGTON'S DISEASE Principal Investigator & Institution: Lesort, Mathieu J.; Assistant Professor; Psychiatry & Behav Neurobiol; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Provided by applicant): Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a pathological expansion of a polyglutamine domain within the protein huntingtin. The precise mechanisms involved in the etiology are still unknown, however there is evidence that impaired mitochondrial function is likely an important factor in HD. A possible clue to the pathogenesis of HD came with the discovery of neuronal intranuclear and cytoplasmic inclusions composed of mutant huntingtin. It has been suggested that Tissue Transglutaminase (tTG) may be a contributing factor to the formation of these aggregates. Tissue TG is a calcium-dependent transamidating enzyme that catalyzed the
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formation of isopeptide bonds between specific proteins to produce insoluble polymeric structures. Recently we have demonstrated that TG activity and tTG levels are significantly increased in specific brain regions affected by the disease as compared to control cases. Further, studies from the laboratory demonstrated that tTG associates with a truncated huntingtin protein and activation of tTG resulted in the modification of specific proteins associated only with the mutant truncated huntingtin protein. These results suggest that tTG may have a role in the etiology of HD. Our working hypothesis is that impaired mitochondrial function results in an increase in tTG activity and this subsequently results in an increased association of tTG with truncated huntingtin and modification of specific mutant huntingtin associated protein. In this proposal the majority of the experiments will be carried out in human neuroblastoma cells that express in a stable or inducible manner, physiological or pathological huntingtin protein constructs. In this proposal we will: (1) test the hypothesis that mitochondria impairment results in an increase in TG activity, and that the presence of mutant huntingtin potentiates this response, (2) test the hypothesis that tTG interacts selectively with the N-terminal truncated huntingtin protein, and that mitochondria impairment results in an increase in this interaction, (3) test the hypothesis that tTG contributes to the formation and/or stabilization of the aggregates, and that mitochondrial impairment may potentiate this effect, and (4) identify the mutant huntingtin-associated proteins that are tTG substrates and test the hypothesis that modification of these proteins may contribute to the selective neuronal death in HD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRAFFICKING DEFECTS IN HUNTINGTONS DISEASE Principal Investigator & Institution: Mcmurray, Cynthia T.; Professor; Mayo Clinic Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (from applicant's abstract) It is the aim of this grant to understand defects in vesicular trafficking and cytoskeleton that may underlie Huntington's disease. Expansion of a trinucleotide repeat CAG, encoding glutamine, results in at least eight progressive neurodegenerative disorders, including Huntington's disease (HD). The mechanism by which polyglutamine expansion selectively kills neurons is largely unknown. Aggregation is generally accepted as part of pathogenesis, but it is not known whether toxicity initiates in the nucleus or the cytoplasm. Using time lapse imaging, we have tracked the localization of huntingtin in individual neurons from expression of the mutant protein to cell death. Toxicity initiates in the cytoplasm of primary neurons. Further, we have identified targets of huntingtin-mediated aggregation directly from aggregates in human brain. We show that the expanded Huntington's protein sequesters tubulin and vesicular trafficking motors into insoluble complexes. Direct video imaging of vesicles indicates that the mutant protein indeed inhibits vesicular transport particularly in the anterograde direction. The motor that is most affected appears to be kinesin and the cargo that appears most affected is mitochondria. Our data support a model for HD pathogenesis in which aggregation inhibits proteolysis of the HD protein, disrupts cytoskeletal architecture and impairs motors required for vesicular/organelle trafficking. In this proposal, we aim to test the hypothesis that sequestration of tubulindependent motors underlies HD regional pathology. Using gel filtration, immunoblotting and immunoprecipitation reactions, we will evaluate whether sequestration of tubulin-dependent complexes underlies HD regional pathology in human brain. By establishing primary cultures of affected and resistant neurons, we will directly test whether vesicular trafficking is altered in the presence of normal and
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expanded HD protein. Since mitochondria are reduced in number in the presence of the mutant huntingtin, we will monitor the fate and subcellular localization of mitochondria by confocal imaging. Alteration in transport will be correlated with the subcellular localization of the HD protein and trafficking motors using fluorescence-labeled proteins and confocal microscopy. Finally, we will refine our understanding of pathogenesis by identifying other proteins present in aggregates by mass spectrometry. The recent observations that tubulin-dependent complexes and vesicular transport may play a role in pathogenesis of ALS and Alzheimer's disease suggest that there may be common aspects to these neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRANSCRIPTIONAL REGULATION OF OXIDATIVE DEATH Principal Investigator & Institution: Ratan, Rajiv R.; Director; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2008 Summary: Huntington's Disease (HD) is an autosomal dominant disorder resulting from selective loss of neurons in the striatum and cerebral cortex. Loss of neurons in HD results from pathological expansion of CAG repeats encoding glutamine. Though the precise mechanisms by which glutamine repeats lead to neuronal loss in HD are unclear, oxidative stress, apoptosis, and transcriptional dysregulation have all been implicated in disease pathogenesis. To understand better oxidative and transcriptional mechanisms that may lead to neuronal loss in HD, we have utilized an in vitro model of oxidative stress in primary cortical neurons. In preliminary studies we have shown that oxidative cell death can be fully abrogated by sequence-selective DNA binding drugs, including mithramycin A (MMA) and chromomcyin A3. These agents are members of the aureolic acid antitumor antibiotics that share a common chromophore, aglycon ring, but differ in the nature of the sugar moieties connected to either side of the aglycone ring. Both antibiotics inhibit transcription during macromoleclar biosynthesis by binding to the "GC" rich transcriptional response elements. To test whether aureolic antibiotics can protect neurons in an in vivo model ofneurodegeneration that may inolve oxidative stress, we examined the effect of MMA in the R6/2 transgenic model of HD. We found that MMA prolongs survival in these mice by nearly 30%, a magnitude superior to any other single neuroprotective agent. These preliminary data are consistent with the overall hypothesis to be tested in this proposal: MMA inhibits neuronal death due to oxidative stress and/or mutant Huntington protein in vitro and in vivo by inhibiting the binding of pro-apoptotic zinc finger transcription factors such as TIEG, and enhancing the DNA binding of pro-survival transcription factors such as CREB. We will examine this hypothesis by determining whether protective concentrations of MMA inhibit TIEG binding to its GC rich DNA binding sites and whether TIEG is critical for oxidative death in cortical neurons. In the second aim, we will determine how MMA affects CREB DNA binding and whether increases in CREB DNA binding contribute to MMA's salutary effects. In the last specific aim, we will compare the mechanism of neuroprotection of MMA to those ofhistone deacetylase inhibitors, another class of transcriptional regulators. These studies will provide critical, mechanistic data on neuroprotective modulators of transcription. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: VESICULAR NEUROTRANSMITTERS
TRANSPORT
OF
AMINO
ACID
Principal Investigator & Institution: Reimer, Richard J.; Neurology & Neurological Scis; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 15-APR-1998; Project End 31-JUL-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “glutamine” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for glutamine in the PubMed Central database: •
[beta]-Glutamate as a Substrate for Glutamine Synthetase. by Robinson P, Neelon K, Schreier HJ, Roberts MF.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93190
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13N isotope studies of glutamine assimilation pathways in Neurospora crassa. by Calderon J, Cooper AJ, Gelbard AS, Mora J.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209816
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A census of glutamine /asparagine-rich regions: Implications for their conserved function and the prediction of novel prions. by Michelitsch MD, Weissman JS.; 2000 Oct 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17268
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A glutamine residue in the membrane-associating domain of the bovine papillomavirus type 1 E5 oncoprotein mediates its binding to a transmembrane component of the vacuolar H(+)-ATPase. by Goldstein DJ, Kulke R, Dimaio D, Schlegel R.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238300
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A Glutamine Transport Gene, glnQ, Is Required for Fibronectin Adherence and Virulence of Group B Streptococci. by Tamura GS, Nittayajarn A, Schoentag DL.; 2002 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=128016
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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A glutamine-amidotransferase-like protein modulates FixT anti-kinase activity in Sinorhizobium meliloti. by Berges H, Checroun C, Guiral S, Garnerone AM, Boistard P, Batut J.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32199
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A Glutamine-Rich Hydrophobic Patch in Transcription Factor Sp1 Contacts the dTAF11110 Component of the Drosophila TFIID Complex and Mediates Transcriptional Activation. by Gill G, Pascal E, Tseng ZH, Tjian R.; 1994 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42912
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A method to assess compositional bias in biological sequences and its application to prion-like glutamine/asparagine-rich domains in eukaryotic proteomes. by Harrison PM, Gerstein M.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=193619
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A mutant lacking the glutamine synthetase gene (glnA) is impaired in the regulation of the nitrate assimilation system in the cyanobacterium Synechocystis sp. strain PCC 6803. by Reyes JC, Florencio FJ.; 1994 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=197208
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A new type of glutamine synthetase in cyanobacteria: the protein encoded by the glnN gene supports nitrogen assimilation in Synechocystis sp. strain PCC 6803. by Reyes JC, Florencio FJ.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205187
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A novel glutamine --RNA interaction identified by screening libraries in mammalian cells. by Tan R, Frankel AD.; 1998 Apr 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22474
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A yeast glutamine tRNA signals nitrogen status for regulation of dimorphic growth and sporulation. by Murray LE, Rowley N, Dawes IW, Johnston GC, Singer RA.; 1998 Jul 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21125
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Activation of transcription by PU.1 requires both acidic and glutamine domains. by Klemsz MJ, Maki RA.; 1996 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231014
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ADP-ribosylation of glutamine synthetase in the cyanobacterium Synechocystis sp. strain PCC 6803. by Silman NJ, Carr NG, Mann NH.; 1995 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=177058
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Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid [beta]peptide of amyloid plaques. by Perutz MF, Pope BJ, Owen D, Wanker EE, Scherzinger E.; 2002 Apr 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=122815
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Alteration of the Bacillus subtilis glutamine synthetase results in overproduction of the enzyme. by Dean DR, Hoch JA, Aronson AI.; 1977 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235556
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Altered regulation of the glnA gene in glutamine synthetase mutants of Bacillus subtilis. by Schreier HJ, Sonenshein AL.; 1986 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212837
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Altered regulation of the glnRA operon in a Bacillus subtilis mutant that produces methionine sulfoximine-tolerant glutamine synthetase. by Schreier HJ, Rostkowski CA, Kellner EM.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=196239
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Amino-terminal deletions define a glutamine amide transfer domain in glutamine phosphoribosylpyrophosphate amidotransferase and other PurF-type amidotransferases. by Mei BG, Zalkin H.; 1990 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209170
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Ammonium assimilation in Rhizobium phaseoli by the glutamine synthetaseglutamate synthase pathway. by Bravo A, Mora J.; 1988 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210751
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An Alternatively Spliced Form of the Transcription Factor Sp1 Containing Only a Single Glutamine-Rich Transactivation Domain. by Persengiev SP, Saffer JD, Kilpatrick DL.; 1995 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40933
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An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel [beta]-fibrils. by Bevivino AE, Loll PJ.; 2001 Oct 9; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59749
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Asparagine and glutamine rotamers: B-factor cutoff and correction of amide flips yield distinct clustering. by Lovell SC, Word JM, Richardson JS, Richardson DC.; 1999 Jan 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15148
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Association of glutamine 27 polymorphism of [beta]2 adrenoceptor with reported childhood asthma: population based study. by Hopes E, McDougall C, Christie G, Dewar J, Wheatley A, Hall IP, Helms PJ.; 1998 Feb 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28470
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Bacillus subtilis citB gene is regulated synergistically by glucose and glutamine. by Rosenkrantz MS, Dingman DW, Sonenshein AL.; 1985 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214224
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Bacillus subtilis glutamine synthetase mutants pleiotropically altered in glucose catabolite repression. by Fisher SH, Sonenshein AL.; 1984 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215290
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Biosynthetic pathways of the osmolytes N epsilon-acetyl-beta-lysine, beta-glutamine, and betaine in Methanohalophilus strain FDF1 suggested by nuclear magnetic resonance analyses. by Roberts MF, Lai MC, Gunsalus RP.; 1992 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207655
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Carbon and Amino Acids Reciprocally Modulate the Expression of Glutamine Synthetase in Arabidopsis. by Oliveira IC, Coruzzi GM.; 1999 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59385
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Characteristics and Efficiency of Glutamine Production by Coupling of a Bacterial Glutamine Synthetase Reaction with the Alcoholic Fermentation System of Baker's Yeast. by Wakisaka S, Ohshima Y, Ogawa M, Tochikura T, Tachiki T.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106798
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Characterization of glutamine-requiring mutants of Pseudomonas aeruginosa. by Janssen DB, Joosten HM, Herst PM, van der Drift C.; 1982 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=220394
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Characterization of the gene encoding glutamine synthetase I (glnA) from Bradyrhizobium japonicum. by Carlson TA, Guerinot ML, Chelm BK.; 1985 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218906
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Cloning and characterization of a glutamine transport operon of Bacillus stearothermophilus NUB36: effect of temperature on regulation of transcription. by Wu L, Welker NE.; 1991 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208167
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Cloning and expression of the Thiobacillus ferrooxidans glutamine synthetase gene in Escherichia coli. by Barros ME, Rawlings DE, Woods DR.; 1985 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=219347
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Cloning and sequencing of the gene encoding glutamine synthetase I from the archaeum Pyrococcus woesei: anomalous phylogenies inferred from analysis of archaeal and bacterial glutamine synthetase I sequences. by Tiboni O, Cammarano P, Sanangelantoni AM.; 1993 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204614
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Cloning of the glutamine synthetase I gene from Rhizobium meliloti. by Somerville JE, Kahn ML.; 1983 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215066
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Cloning, Expression, and Purification of Glutamine Synthetase from Clostridium acetobutylicum. by Usdin KP, Zappe H, Jones DT, Woods DR.; 1986 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=203548
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Cloning, nucleotide sequence, and potential regulatory elements of the glutamine synthetase gene from murine 3T3-L1 adipocytes. by Bhandari B, Beckwith KD, Miller RE.; 1988 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=281850
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Cloning, primary structure, and regulation of the HIS7 gene encoding a bifunctional glutamine amidotransferase: cyclase from Saccharomyces cerevisiae. by Kuenzler M, Balmelli T, Egli CM, Paravicini G, Braus GH.; 1993 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206611
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Close linkage of genes encoding glutamine synthetases I and II in Frankia alni CpI1. by Hosted TJ, Rochefort DA, Benson DR.; 1993 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=204773
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Combined, Functional Genomic-Biochemical Approach to Intermediary Metabolism: Interaction of Acivicin, a Glutamine Amidotransferase Inhibitor, with Escherichia coli K-12. by Smulski DR, Huang LL, McCluskey MP, Reeve MJ, Vollmer AC, Van Dyk TK, LaRossa RA.; 2001 Jun 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99633
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Comparative Biochemical and Immunological Studies of Bacterial Glutamine Synthetases. by Tronick SR, Ciardi JE, Stadtman ER.; 1973 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246329
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Concerted hexose transport curb by tunicamycin is rendered irreversible by glucose or allose in medium containing L-glutamine. by Ullrey DB, Kalckar HM.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287266
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Conformational effects of substituting amino acids for glutamine-61 on the central transforming region of the P21 proteins. by Pincus MR, Brandt-Rauf PW, Carty RP, Lubowsky J, Avitable M, Gibson KD, Scheraga HA.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299545
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Conservation of Glutamine-Rich Transactivation Function between Yeast and Humans. by Escher D, Bodmer-Glavas M, Barberis A, Schaffner W.; 2000 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=85493
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Constitutive Overexpression of Cytosolic Glutamine Synthetase (GS1) Gene in Transgenic Alfalfa Demonstrates That GS1 May Be Regulated at the Level of RNA Stability and Protein Turnover. by Ortega JL, Temple SJ, Sengupta-Gopalan C.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102286
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Contribution of a Thickened Cell Wall and Its Glutamine Nonamidated Component to the Vancomycin Resistance Expressed by Staphylococcus aureus Mu50. by Cui L, Murakami H, Kuwahara-Arai K, Hanaki H, Hiramatsu K.; 2000 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=90058
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Control of ftsZ Expression, Cell Division, and Glutamine Metabolism in LuriaBertani Medium by the Alarmone ppGpp in Escherichia coli. by Powell BS, Court DL.; 1998 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106991
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Crystal structure of a dimeric chymotrypsin inhibitor 2 mutant containing an inserted glutamine repeat. by Chen YW, Stott K, Perutz MF.; 1999 Feb 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=15450
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Cytosolic Glutamine Synthetase in Soybean Is Encoded by a Multigene Family, and the Members Are Regulated in an Organ-Specific and Developmental Manner. by Morey KJ, Ortega JL, Sengupta-Gopalan C.; 2002 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=148970
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Derepression of nitrogenase activity in glutamine auxotrophs of Rhodopseudomonas capsulata. by Wall JD, Gest H.; 1979 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218340
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Determination of the rate of the glutamate /glutamine cycle in the human brain by in vivo 13C NMR. by Shen J, Petersen KF, Behar KL, Brown P, Nixon TW, Mason GF, Petroff OA, Shulman GI, Shulman RG, Rothman DL.; 1999 Jul 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22218
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Diel Rhythms in Ribulose-1,5-Bisphosphate Carboxylase/Oxygenase and Glutamine Synthetase Gene Expression in a Natural Population of Marine Picoplanktonic Cyanobacteria (Synechococcus spp.). by Wyman M.; 1999 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=91547
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Differential expression of a Clostridium acetobutylicum antisense RNA: implications for regulation of glutamine synthetase. by Fierro-Monti IP, Reid SJ, Woods DR.; 1992 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207476
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Differential transcription of the two glutamine synthetase genes of Bradyrhizobium japonicum. by Carlson TA, Martin GB, Chelm BK.; 1987 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214189
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Distinct Subdomains of Human TAFII130 Are Required for Interactions with Glutamine-Rich Transcriptional Activators. by Saluja D, Vassallo MF, Tanese N.; 1998 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109159
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Distribution of Glutamine and Asparagine Residues and Their Near Neighbors in Peptides and Proteins. by Robinson AB, Robinson LR.; 1991 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=52614
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Effect of glutamine on enzymes of nitrogen metabolism in Bacillus subtilis. by Deshpande KL, Katze JR, Kane JF.; 1981 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217177
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Effect of glutamine on growth and heterocyst differentiation in the cyanobacterium Anabaena variabilis. by Thiel T, Leone M.; 1986 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213549
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Effects of Ammonium, -Glutamate, and -Glutamine on Nitrogen Catabolism in Aspergillus nidulans. by Hynes MJ.; 1974 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245890
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Effects of glutamines and glutamates at sites of covalent modification of a methylaccepting transducer. by Park C, Dutton DP, Hazelbauer GL.; 1990 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210843
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Effects of l-Glutamine Deprivation on Growth of HVJ (Sendai Virus) in BHK Cells. by Ito Y, Kimura Y, Nagata I, Kunii A.; 1974 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=355338
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Effects of Salmonella typhimurium Infection and Ofloxacin Treatment on Glucose and Glutamine Metabolism in Caco-2/TC-7 Cells. by Posho L, Delbos-Bocage L, Gueylard D, Farinotti R, Carbon C.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=105971
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Electrogenic glutamine uptake by Peptostreptococcus anaerobius and generation of a transmembrane potential. by Beck BJ, Russell JB.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205193
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Electron Transport Controls Glutamine Synthetase Activity in the Facultative Heterotrophic Cyanobacterium Synechocystis sp. PCC 6803. by Reyes JC, Crespo JL, Garcia-Dominguez M, Florencio FJ.; 1995 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=161391
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Enzymatic synthesis of aminocyclitol moieties of aminoglycoside antibiotics from inositol by Streptomyces spp.: detection of glutamine-aminocyclitol aminotransferase and diaminocyclitol aminotransferase activities in a spectinomycin producer. by Walker JB.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176663
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Expression of the Bacillus subtilis glutamine synthetase gene in Escherichia coli. by Gardner AL, Aronson AI.; 1984 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215536
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Fe2 +-Tetracycline-Mediated Cleavage of the Tn10 Tetracycline Efflux Protein TetA Reveals a Substrate Binding Site near Glutamine 225 in Transmembrane Helix 7. by McMurry LM, Aldema-Ramos ML, Levy SB.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=135328
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Feedback inhibition of ammonium (methylammonium) ion transport in Escherichia coli by glutamine and glutamine analogs. by Jayakumar A, Hong JS, Barnes EM Jr.; 1987 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211813
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Formation of glutamine from [13n]ammonia, [13n]dinitrogen, and [14C]glutamate by heterocysts isolated from Anabaena cylindrica. by Thomas J, Meeks JC, Wolk CP, Shaffer PW, Austin SM.; 1977 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235134
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Genetic and biochemical characterization of glutamine synthetase from Neurospora crassa glutamine auxotrophs and their revertants. by Davila G, Brom S, Mora Y, Palacios R, Mora J.; 1983 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217941
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Genetic and Physiological Analysis of Germination Efficiency in Maize in Relation to Nitrogen Metabolism Reveals the Importance of Cytosolic Glutamine Synthetase. by Limami AM, Rouillon C, Glevarec G, Gallais A, Hirel B.; 2002 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166697
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Genetic control of glutamine synthetase in Klebiella aerogenes. by Streicher SL, Bender RA, Magasanik B.; 1975 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285646
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Genetic selection for active E.coli amber tRNA(Asn) exclusively led to glutamine inserting suppressors. by Martin F, Eriani G, Reinbolt J, Dirheimer G, Gangloff J.; 1995 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306759
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Genetics and physiology of Neurospora crassa glutamine auxotrophs. by Davila G, Sanchez F, Palacios R, Mora J.; 1978 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222312
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Genetics of the glutamine transport system in Escherichia coli. by Masters PS, Hong JS.; 1981 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216116
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Glutamine /proline-rich PQE-1 proteins protect Caenorhabditis elegans neurons from huntingtin polyglutamine neurotoxicity. by Faber PW, Voisine C, King DC, Bates EA, Hart AC.; 2002 Dec 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=139281
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Glutamine and glutamate transport by Anabaena variabilis. by Chapman JS, Meeks JC.; 1983 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=215059
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Glutamine and proline accumulation by Staphylococcus aureus with reduction in water activity. by Anderson CB, Witter LD.; 1982 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=244260
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Glutamine and related analogs regulate guanosine monophosphate reductase in Salmonella typhimurium. by Garber BB, Jochimsen BU, Gots JS.; 1980 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=294189
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Glutamine as a feedback inhibitor of the Rhodopseudomonas sphaeroides nitrogenase system. by Jones BL, Monty KJ.; 1979 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218049
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Glutamine auxotrophs of Bacillus subtilis that overproduce glutamine synthetase antigen have altered conserved amino acids in or near the active site. by Zhang J, Strauch M, Aronson AI.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210090
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Glutamine Repeats as Polar Zippers: Their Possible Role in Inherited Neurodegenerative Diseases. by Perutz MF, Johnson T, Suzuki M, Finch JT.; 1994 Jun 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43993
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Glutamine synthesis is a regulatory signal controlling glucose catabolism in Saccharomyces cerevisiae. by Flores-Samaniego B, Olivera H, Gonzalez A.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=206930
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Glutamine synthetase and nitrogen cycling in colonies of the marine diazotrophic cyanobacteria Trichodesmium spp. by Carpenter EJ, Bergman B, Dawson R, Siddiqui PJ, Soderback E, Capone DG.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183058
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Glutamine Synthetase GlnA1 Is Essential for Growth of Mycobacterium tuberculosis in Human THP-1 Macrophages and Guinea Pigs. by Tullius MV, Harth G, Horwitz MA.; 2003 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=162033
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Glutamine synthetase of Klebsiella aerogenes: genetic and physiological properties of mutants in the adenylylation system. by Janssen KA, Magasanik B.; 1977 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235039
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Glutamine synthetase of pseudomonads: some biochemical and physicochemical properties. by Meyer JM, Stadtman ER.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217015
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Glutamine synthetase protects against neuronal degeneration in injured retinal tissue. by Gorovits R, Avidan N, Avisar N, Shaked I, Vardimon L.; 1997 Jun 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=21278
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Glutamine-stimulated amino acid and peptide incorporation in Bacteroides melaninogenicus. by Lev M.; 1980 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=294358
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Glu-tRNAGln amidotransferase: A novel heterotrimeric enzyme required for correct decoding of glutamine codons during translation. by Curnow AW, Hong KW, Yuan R, Kim SI, Martins O, Winkler W, Henkin TM, Soll D.; 1997 Oct 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23611
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Gut mucosal and plasma concentrations of glutamine: a comparison between two enriched enteral feeding solutions in critically ill patients. by Preiser JC, Peres-Bota D, Eisendrath P, Vincent JL, Van Gossum A.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=270008
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Helicobacter pylori Glutamine Synthetase Lacks Features Associated with Transcriptional and Posttranslational Regulation. by Garner RM, Fulkerson J Jr, Mobley HL.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=108133
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Heterogeneity in the polyglutamine tract of the glucocorticoid receptor from different rat strains. by Gearing KL, Gustafsson JA, Okret S.; 1993 Apr 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=309449
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High Extracellular Levels of Mycobacterium tuberculosis Glutamine Synthetase and Superoxide Dismutase in Actively Growing Cultures Are Due to High Expression and Extracellular Stability Rather than to a Protein-Specific Export Mechanism. by Tullius MV, Harth G, Horwitz MA.; 2001 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98770
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Identification of the structural gene for glutamine synthetase in Klebsiella aerogenes. by Deleo AB, Magasanik B.; 1975 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285645
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Immunochemical characterization of glutamine synthetase from Neurospora crassa glutamine auxotrophs. by Sanchez F, Davila G, Mora J, Palacios R.; 1979 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216901
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In Situ Glutamine Synthetase Activity in a Marine Unicellular Alga (Development of a Sensitive Colorimetric Assay and the Effects of Nitrogen Status on Enzyme Activity). by Rees T, Larson TR, Heldens J, Huning F.; 1995 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157675
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In vivo 13C NMR measurements of cerebral glutamine synthesis as evidence for glutamate --glutamine cycling. by Sibson NR, Dhankhar A, Mason GF, Behar KL, Rothman DL, Shulman RG.; 1997 Mar 18; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=20152
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In Vivo Regulation of Glutamine Synthetase Activity in the Marine Chlorophyll bContaining Cyanobacterium Prochlorococcus sp. Strain PCC 9511 (Oxyphotobacteria). by El Alaoui S, Diez J, Humanes L, Toribio F, Partensky F, Garcia-Fernandez JM.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92856
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Incorporation of Glutamine Repeats Makes Protein Oligomerize: Implications for Neurodegenerative Diseases. by Stott K, Blackburn JM, Butler PJ, Perutz M.; 1995 Jul 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41547
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Inhibition of Glutamate Transport in Synechococcus cedrorum by Glutamine. by Wan AY, Floyd KW, Hatch MT.; 1975 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=235998
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Inhibition of Mycobacterium tuberculosis Glutamine Synthetase as a Novel Antibiotic Strategy against Tuberculosis: Demonstration of Efficacy In Vivo. by Harth G, Horwitz MA.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=143262
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Isolation and characterization of a Neurospora crassa mutant altered in the alpha polypeptide of glutamine synthetase. by Calderon J, Martinez LM, Mora J.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213155
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Isolation of Klebsiella aerogenes mutants cis-dominant for glutamine synthetase expression. by Rothstein DM, Magasanik B.; 1980 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=293674
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Isolation, characterization, and complementation of Rhizobium meliloti 104A14 mutants that lack glutamine synthetase II activity. by Somerville JE, Shatters RG, Kahn ML.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210320
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Kinetic properties of a phosphate-bond-driven glutamate-glutamine transport system in Streptococcus lactis and Streptococcus cremoris. by Poolman B, Smid EJ, Konings WN.; 1987 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212181
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l-Glutamine as a Substrate for l-Asparaginase from Serratia marcescens. by Novak EK, Phillips AW.; 1974 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285550
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L-Glutamine formation by Flavobacterium rigense. by Yamada S, Nabe K, Ujimaru T, Izuo N, Chibata I.; 1979 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=243354
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Lipase and Its Modulator from Pseudomonas sp. Strain KFCC 10818: Proline-toGlutamine Substitution at Position 112 Induces Formation of Enzymatically Active Lipase in the Absence of the Modulator. by Kim EK, Jang WH, Ko JH, Kang JS, Noh MJ, Yoo OJ.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99672
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Long-term regulation of neuronal high-affinity glutamate and glutamine uptake in Aplysia. by Levenson J, Endo S, Kategaya LS, Fernandez RI, Brabham DG, Chin J, Byrne JH, Eskin A.; 2000 Nov 7; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18854
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Mechanism of -Glutamine Production by an -Glutamine-Producing Mutant of Flavobacterium rigense. by Nabe K, Yamada S, Chibata I.; 1981 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=244069
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Metabolic regulation of the gene encoding glutamine-dependent asparagine synthetase in Arabidopsis thaliana. by Lam HM, Peng SS, Coruzzi GM.; 1994 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=159672
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Methionine sulfoxide is transported by high-affinity methionine and glutamine transport systems in Salmonella typhimurium. by Ayling PD.; 1981 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216234
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Molecular analysis of the Azotobacter vinelandii glnA gene encoding glutamine synthetase. by Toukdarian A, Saunders G, Selman-Sosa G, Santero E, Woodley P, Kennedy C.; 1990 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213009
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Molecular and regulatory properties of glutamine synthetase from the phototrophic bacterium Rhodopseudomonas capsulata E1F1. by Caballero FJ, Cejudo FJ, Florencio FJ, Cardenas J, Castillo F.; 1985 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218924
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Molecular Basis of a Null Mutation in Soybean Lipoxygenase 2: Substitution of Glutamine for an Iron-Ligand Histidine. by Wang WH, Takano T, Shibata D, Kitamura K, Takeda G.; 1994 Jun 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=44090
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Mutational Analysis of Bacillus subtilis Glutamine Phosphoribosylpyrophosphate Amidotransferase Propeptide Processing. by Li S, Smith JL, Zalkin H.; 1999 Mar 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93527
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Mutations affecting glutamine synthetase activity in Salmonella typhimurium. by Kustu SG, McKereghan K.; 1975 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246153
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Mutations that alter the covalent modification of glutamine synthetase in Salmonella typhimurium. by Bancroft S, Rhee SG, Neumann C, Kustu S.; 1978 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222354
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Na +/Glutamine (Asparagine) Cotransport by Staphylococcus lugdunensis and Corynebacterium amycolatum. by Sarker RI, Maloney PC.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94982
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Natural UAG suppressor glutamine tRNA is elevated in mouse cells infected with Moloney murine leukemia virus. by Kuchino Y, Beier H, Akita N, Nishimura S.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304719
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Neurospora crassa mutant impaired in glutamine regulation. by Gonzalez A, Tenorio M, Vaca G, Mora J.; 1983 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217643
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New class of Bacillus subtilis glutamine-requiring mutants. by Reysset G.; 1981 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216252
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Nitrogen control of Salmonella typhimurium: co-regulation of synthesis of glutamine synthetase and amino acid transport systems. by Kustu SG, McFarland NC, Hui SP, Esmon B, Ames GF.; 1979 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218260
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Nitrogen source regulates glutamine synthetase mRNA levels in Neurospora crassa. by Sanchez F, Campomanes M, Quinto C, Hansberg W, Mora J, Palacios R.; 1978 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218521
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Normal Myeloid Development Requires Both the Glutamine-Rich Transactivation Domain and the PEST Region of Transcription Factor PU.1 but Not the Potent Acidic Transactivation Domain. by Fisher RC, Olson MC, Pongubala JM, Perkel JM, Atchison ML, Scott EW, Simon MC.; 1998 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=109018
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Nuclear respiratory factors 1 and 2 utilize similar glutamine-containing clusters of hydrophobic residues to activate transcription. by Gugneja S, Virbasius CM, Scarpulla RC.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231571
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Omega-amidase pathway in the degradation of glutamine in Neurospora crassa. by Calderon J, Morett E, Mora J.; 1985 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214962
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Organization and nucleotide sequence of the glutamine synthetase (glnA) gene from Lactobacillus delbrueckii subsp. bulgaricus. by Ishino Y, Morgenthaler P, Hottinger H, Soll D.; 1992 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=183065
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Overexpression of Cytosolic Glutamine Synthetase. Relation to Nitrogen, Light, and Photorespiration. by Oliveira IC, Brears T, Knight TJ, Clark A, Coruzzi GM.; 2002 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166511
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Oxidative Turnover of Soybean Root Glutamine Synthetase. In Vitro and in Vivo Studies. by Ortega JL, Roche D, Sengupta-Gopalan C.; 1999 Apr 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32034
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Oxygen-dependent inactivation of glutamine phosphoribosylpyrophosphate amidotransferase in stationary-phase cultures of Bacillus subtilis. by Turnbough CL Jr, Switzer RL.; 1975 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285619
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Oxygen-dependent inactivation of glutamine phosphoribosylpyrophosphate amidotransferase in vitro inactivation. by Turnbough CL Jr, Switzer RL.; 1975 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285620
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Pathway of proton transfer in bacterial reaction centers: replacement of glutamic acid 212 in the L subunit by glutamine inhibits quinone (secondary acceptor) turnover. by Paddock ML, Rongey SH, Feher G, Okamura MY.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=297892
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Peptides containing glutamine repeats as substrates for transglutaminase-catalyzed cross-linking: Relevance to diseases of the nervous system. by Kahlem P, Terre C, Green H, Djian P.; 1996 Dec 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26176
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Peroxynitrite-Mediated Nitration of Tyrosine Residues in Escherichia coli Glutamine Synthetase Mimics Adenylylation: Relevance to Signal Transduction. by Berlett BS, Friguet B, Yim MB, Chock PB, Stadtman ER.; 1996 Mar 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39857
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Photorespiratory NH4 + Production in Leaves of Wild-Type and Glutamine Synthetase 2 Antisense Oilseed Rape. by Husted S, Mattsson M, Mollers C, Wallbraun M, Schjoerring JK.; 2002 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166624
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Phytochrome-Mediated Photoperiod Perception, Shoot Growth, Glutamine, Calcium, and Protein Phosphorylation Influence the Activity of the Poplar Bark Storage Protein Gene Promoter (bspA). by Zhu B, Coleman GD.; 2001 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=102308
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Poliovirus capsid proteins derived from P1 precursors with glutamine-valine cleavage sites have defects in assembly and RNA encapsidation. by Ansardi DC, Morrow CD.; 1993 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238192
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Promoter-specific transactivation of hepatitis B virus transcription by a glutamineand proline-rich domain of hepatocyte nuclear factor 1. by Raney AK, Easton AJ, Milich DR, McLachlan A.; 1991 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=250238
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Properties of the Bacillus licheniformis A5 glutamine synthetase purified from cells grown in the presence of ammonia or nitrate. by Donohue TJ, Bernlohr RW.; 1981 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216080
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Purification of PII and PII-UMP and In Vitro Studies of Regulation of Glutamine Synthetase in Rhodospirillum rubrum. by Johansson M, Nordlund S.; 1999 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=103790
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Rapid biosynthesis of N-linolenoyl-l-glutamine, an elicitor of plant volatiles, by membrane-associated enzyme(s) in Manduca sexta. by Lait CG, Alborn HT, Teal PE, Tumlinson JH III.; 2003 Jun 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=165824
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Reactions catalyzed by purified L-glutamine: keto-scyllo-inositol aminotransferase, an enzyme required for biosynthesis of aminocyclitol antibiotics. by Lucher LA, Chen YM, Walker JB.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=172459
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Regulation of a glutamine amidotransferase subunit from Bacillus subtilis by a cloned trpE gene from Bacillus pumilus. by Kane JF, Hill RJ.; 1980 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=293734
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Regulation of Anabaena sp. strain PCC 7120 glutamine synthetase activity in a Synechocystis sp. strain PCC 6803 derivative strain bearing the Anabaena glnA gene and a mutated host glnA gene. by Merida A, Flores E, Florencio FJ.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205765
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Regulation of Bacillus subtilis glutamine phosphoribosylpyrophosphate amidotransferase inactivation in vivo. by Bernlohr DA, Switzer RL.; 1983 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221717
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Regulation of enzyme formation in Klebsiella aerogenes by episomal glutamine synthetase of Escherichia coli. by Streicher SL, Deleo AB, Magasanik B.; 1976 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=233050
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Regulation of glutamine synthesis by glycine and serine in Neurospora crassa. by Hernandez G, Mora Y, Mora J.; 1986 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214380
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Regulation of glutamine synthetase activity in the unicellular cyanobacterium Synechocystis sp. strain PCC 6803 by the nitrogen source: effect of ammonium. by Merida A, Candau P, Florencio FJ.; 1991 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208058
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Regulation of glutamine synthetase by regulatory protein PII in Klebsiella aerogenes mutants lacking adenylyltransferase. by Reuveny Z, Foor F, Magasanik B.; 1981 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217020
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Regulation of glutamine synthetase formation in Escherichia coli: characterization of mutants lacking the uridylyltransferase. by Bloom FR, Levin MS, Foor F, Tyler B.; 1978 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222288
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Regulation of glutamine synthetase II activity in Rhizobium meliloti 104A14. by Shatters RG, Somerville JE, Kahn ML.; 1989 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210321
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Regulation of Glutamine Synthetase II. Patterns of Feedback Inhibition in Microorganisms. by Hubbard JS, Stadtman ER.; 1967 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276552
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Regulation of glutamine synthetase in Streptomyces coelicolor. by Fisher SH, Wray LV Jr.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209911
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Regulation of Glutamine Synthetase V. Partial Purification and Properties of Glutamine Synthetase from Bacillus licheniformis. by Hubbard JS, Stadtman ER.; 1967 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276769
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Regulation of Glutamine Synthetase VI. Interactions of Inhibitors for Bacillus licheniformis Glutamine Synthetase. by Hubbard JS, Stadtman ER.; 1967 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276770
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Regulation of Glutamine Synthetase X. Effect of Growth Conditions on the Susceptibility of Escherichia coli Glutamine Synthetase to Feedback Inhibition. by Kingdon HS, Stadtman ER.; 1967 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=276760
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Regulation of Glutamine Transport in Escherichia coli. by Willis RC, Iwata KK, Furlong CE.; 1975 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=246156
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Regulation of Nitrogen Fixation in Klebsiella pneumoniae: Evidence for a Role of Glutamine Synthetase as a Regulator of Nitrogenase Synthesis. by Streicher SL, Shanmugam KT, Ausubel F, Morandi C, Goldberg RB.; 1974 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=245843
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Regulation of nitrogen metabolism in glutamine auxotrophs of Klebsiella pneumoniae. by Leonardo JM, Goldberg RB.; 1980 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=293910
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Regulation of Synthesis of Glutamine Synthase in Bacillus subtilis. by Rebello JL, Strauss N.; 1969 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=284872
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Regulation of the activity of the Bacillus licheniformis A5 glutamine synthetase. by Donohue TJ, Bernlohr RW.; 1981 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216179
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Regulation of the biosynthesis of aminoacyl-transfer ribonucleic acid synthetases and of transfer ribonucleic acid in Escherichia coli. VI. Mutants with increased levels of glutaminyl-transfer ribonucleic acid synthetase and of glutamine transfer ribonucleic acid. by Cheung A, Morgan S, Low KB, Soll D.; 1979 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216843
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Regulation of the glutamate-glutamine transport system by intracellular pH in Streptococcus lactis. by Poolman B, Hellingwerf KJ, Konings WN.; 1987 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212150
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Regulatory mutations in the Klebsiella aerogenes structural gene for glutamine synthetase. by Bender RA, Magasanik B.; 1977 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=221831
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Relation between the adenylylation state of glutamine synthetase and the expression of other genes involved in nitrogen metabolism. by Goldberg RB, Hanau R.; 1979 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218311
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Repression of nitrate reductase in Neurospora studied by using L-methionine-DLsulfoximine and glutamine auxotroph gln-1b. by Premakumar R, Sorger GJ, Gooden D.; 1980 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=294258
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Requirement for membrane potential in active transport of glutamine by Escherichia coli. by Plate CA.; 1979 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218439
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Rhizobium meliloti 1021 has three differentially regulated loci involved in glutamine biosynthesis, none of which is essential for symbiotic nitrogen fixation. by de Bruijn FJ, Rossbach S, Schneider M, Ratet P, Messmer S, Szeto WW, Ausubel FM, Schell J.; 1989 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=209797
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Role of glnA-linked genes in regulation of glutamine synthetase and histidase formation in Klebsiella aerogenes. by Rothman N, Rothstein D, Foor F, Magasanik B.; 1982 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=220102
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Role of Glutamine 17 of the Bovine Papillomavirus E5 Protein in Platelet-Derived Growth Factor [beta] Receptor Activation and Cell Transformation. by Klein O, Polack GW, Surti T, Kegler-Ebo D, Smith SO, DiMaio D.; 1998 Nov; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110309
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Role of Glutamine Synthetase in Nitrogen Metabolite Repression in Aspergillus nidulans. by Margelis S, D'Souza C, Small AJ, Hynes MJ, Adams TH, Davis MA.; 2001 Oct 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99658
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Role of glutamine synthetase in the uptake and metabolism of methylammonium by Azotobacter vinelandii. by Barnes EM Jr, Zimniak P, Jayakumar A.; 1983 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217892
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Role of Glutamine-117 in the Ribonucleolytic Activity of Human Angiogenin. by Russo N, Shapiro R, Acharya KR, Riordan JF, Vallee BL.; 1994 Apr 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43486
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Salmonella typhimurium LT-2 mutants with altered glutamine synthetase levels and amino acid uptake activities. by Funanage VL, Ayling PD, Dendinger SM, Brenchley JE.; 1978 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=218583
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Search for revertants of the glutamine mischarging mutans of Escherichia coli su+3 tyrosine suppressor tRNA that are able to insert tyrosine at the site of amber mutation. by Celis JE, Squire M, Kaltoft K, Riisom E.; 1977 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=342609
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Sequence of the GLN1 gene of Saccharomyces cerevisiae: role of the upstream region in regulation of glutamine synthetase expression. by Minehart PL, Magasanik B.; 1992 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205784
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Simultaneous prevention of glutamine synthesis and high-affinity transport attenuates Salmonella typhimurium virulence. by Klose KE, Mekalanos JJ.; 1997 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=176100
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Stimulation of glutamine transport by osmotic stress in Escherichia coli K-12. by Gehring K, Hofnung M, Nikaido H.; 1990 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213319
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Streptomyces hygroscopicus has two glutamine synthetase genes. by Kumada Y, Takano E, Nagaoka K, Thompson CJ.; 1990 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=213198
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Structural role for a conserved region in the CTP synthetase glutamine amide transfer domain. by Weng ML, Zalkin H.; 1987 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=212343
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Subunit Interactions and Glutamine Utilization by Escherichia coli Imidazole Glycerol Phosphate Synthase. by Klem TJ, Chen Y, Davisson VJ.; 2001 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94967
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Suppression of a deletion mutation in the glutamine amidotransferase region of the Salmonella typhimurium trpD gene by mutations in pheA and tyrA. by Tanemura S, Bauerle R.; 1979 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=216906
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Switching tRNAGln Identity from Glutamine to Tryptophan. by Rogers MJ, Adachi T, Inokuchi H, Soll D.; 1992 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=48888
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Temperature-Dependent Function of the Glutamine Phosphoribosylpyrophosphate Amidotransferase Ammonia Channel and Coupling with Glycinamide Ribonucleotide Synthetase in a Hyperthermophile. by Bera AK, Chen S, Smith JL, Zalkin H.; 2000 Jul 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=94544
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The actinorhizal root-nodule symbiont Frankia sp. strain CpI1 has two glutamine synthetases. by Edmands J, Noridge NA, Benson DR.; 1987 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=299021
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The central hydrophobic domain of the bovine papillomavirus E5 transforming protein can be functionally replaced by many hydrophobic amino acid sequences containing a glutamine. by Kulke R, Horwitz BH, Zibello T, DiMaio D.; 1992 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=238311
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The femC locus of Staphylococcus aureus required for methicillin resistance includes the glutamine synthetase operon. by Gustafson J, Strassle A, Hachler H, Kayser FH, Berger-Bachi B.; 1994 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205213
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The glutamine-rich activation domains of human Sp1 do not stimulate transcription in Saccharomyces cerevisiae. by Ponticelli AS, Pardee TS, Struhl K.; 1995 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231990
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The hemK gene in Escherichia coli encodes the N5-glutamine methyltransferase that modifies peptide release factors. by Heurgue-Hamard V, Champ S, Engstrom A, Ehrenberg M, Buckingham RH.; 2002 Feb 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=125846
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The Metastatic Suppressor Nm23-H1 Interacts with EBNA3C at Sequences Located between the Glutamine- and Proline-Rich Domains and Can Cooperate in Activation of Transcription. by Subramanian C, Robertson ES.; 2002 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=136985
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The Saccharomyces cerevisiae YCC5 (YCL025c) Gene Encodes an Amino Acid Permease, Agp1, Which Transports Asparagine and Glutamine. by Schreve JL, Sin JK, Garrett JM.; 1998 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107201
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The structures of anthranilate synthase of Serratia marcescens crystallized in the presence of (i) its substrates, chorismate and glutamine, and a product, glutamate, and (ii) its end-product inhibitor, l-tryptophan. by Spraggon G, Kim C, Nguyen-Huu X, Yee MC, Yanofsky C, Mills SE.; 2001 May 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33415
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The Synechococcus Strain PCC 7942 glnN Product (Glutamine Synthetase III) Helps Recovery from Prolonged Nitrogen Chlorosis. by Sauer J, Dirmeier U, Forchhammer K.; 2000 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=111011
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The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine. by Crespo JL, Powers T, Fowler B, Hall MN.; 2002 May 14; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=124480
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Transport of glutamine by Streptococcus bovis and conversion of glutamine to pyroglutamic acid and ammonia. by Chen GJ, Russell JB.; 1989 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210004
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Treatment of Mycobacterium tuberculosis with antisense oligonucleotides to glutamine synthetase mRNA inhibits glutamine synthetase activity, formation of the poly-l-glutamate /glutamine cell wall structure, and bacterial replication. by Harth G, Zamecnik PC, Tang JY, Tabatadze D, Horwitz MA.; 2000 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26678
The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with glutamine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “glutamine” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for glutamine (hyperlinks lead to article summaries): •
A brain-specific isoform of small glutamine-rich tetratricopeptide repeat-containing protein binds to Hsc70 and the cysteine string protein. Author(s): Tobaben S, Varoqueaux F, Brose N, Stahl B, Meyer G. Source: The Journal of Biological Chemistry. 2003 October 3; 278(40): 38376-83. Epub 2003 July 23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878599&dopt=Abstract
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A census of glutamine/asparagine-rich regions: implications for their conserved function and the prediction of novel prions. Author(s): Michelitsch MD, Weissman JS. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 October 24; 97(22): 11910-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050225&dopt=Abstract
6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A glutamine transport gene, glnQ, is required for fibronectin adherence and virulence of group B streptococci. Author(s): Tamura GS, Nittayajarn A, Schoentag DL. Source: Infection and Immunity. 2002 June; 70(6): 2877-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12010975&dopt=Abstract
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A method to assess compositional bias in biological sequences and its application to prion-like glutamine/asparagine-rich domains in eukaryotic proteomes. Author(s): Harrison PM, Gerstein M. Source: Genome Biology. 2003; 4(6): R40. Epub 2003 May 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801414&dopt=Abstract
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A novel glutamine-rich putative transcriptional adaptor protein (TIG-1), preferentially expressed in placental and bone-marrow tissues. Author(s): Abraham S, Solomon WB. Source: Gene. 2000 September 19; 255(2): 389-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11024300&dopt=Abstract
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A novel variant of glutamine: fructose-6-phosphate amidotransferase-1 (GFAT1) mRNA is selectively expressed in striated muscle. Author(s): DeHaven JE, Robinson KA, Nelson BA, Buse MG. Source: Diabetes. 2001 November; 50(11): 2419-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679416&dopt=Abstract
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A radiometric assay for glutamine:fructose-6-phosphate amidotransferase. Author(s): Broschat KO, Gorka C, Kasten TP, Gulve EA, Kilpatrick B. Source: Analytical Biochemistry. 2002 June 1; 305(1): 10-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12018941&dopt=Abstract
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A randomized, controlled trial of parenteral glutamine in ill, very low birth-weight neonates. Author(s): Thompson SW, McClure BG, Tubman TR. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 5503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581795&dopt=Abstract
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Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study. Author(s): des Robert C, Le Bacquer O, Piloquet H, Roze JC, Darmaun D. Source: Pediatric Research. 2002 January; 51(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756645&dopt=Abstract
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Acute enteral glutamine infusion enhances heme oxygenase-1 expression in human duodenal mucosa. Author(s): Coeffier M, Le Pessot F, Leplingard A, Marion R, Lerebours E, Ducrotte P, Dechelotte P. Source: The Journal of Nutrition. 2002 September; 132(9): 2570-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221210&dopt=Abstract
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Acute mania is accompanied by elevated glutamate/glutamine levels within the left dorsolateral prefrontal cortex. Author(s): Michael N, Erfurth A, Ohrmann P, Gossling M, Arolt V, Heindel W, Pfleiderer B. Source: Psychopharmacology. 2003 July; 168(3): 344-6. Epub 2003 April 09. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684737&dopt=Abstract
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Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid betapeptide of amyloid plaques. Author(s): Perutz MF, Pope BJ, Owen D, Wanker EE, Scherzinger E. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 April 16; 99(8): 5596-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11960015&dopt=Abstract
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Altered proteasomal function due to the expression of polyglutamine-expanded truncated N-terminal huntingtin induces apoptosis by caspase activation through mitochondrial cytochrome c release. Author(s): Jana NR, Zemskov EA, Wang Gh, Nukina N. Source: Human Molecular Genetics. 2001 May 1; 10(10): 1049-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331615&dopt=Abstract
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Altered response to oral glutamine challenge as prognostic factor for overt episodes in patients with minimal hepatic encephalopathy. Author(s): Romero-Gomez M, Grande L, Camacho I, Benitez S, Irles JA, Castro M. Source: Journal of Hepatology. 2002 December; 37(6): 781-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445419&dopt=Abstract
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Amyloid-like features of polyglutamine aggregates and their assembly kinetics. Author(s): Chen S, Berthelier V, Hamilton JB, O'Nuallain B, Wetzel R. Source: Biochemistry. 2002 June 11; 41(23): 7391-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044172&dopt=Abstract
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An alternative method to supplement glutamine in parenteral nutrition? Author(s): Sandifer DP. Source: Critical Care Medicine. 2000 November; 28(11): 3761-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098992&dopt=Abstract
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An arginine/glutamine difference at the juxtaposition of transmembrane domain 6 and the third extracellular loop contributes to the markedly different nucleotide selectivities of human and canine P2Y11 receptors. Author(s): Qi AD, Zambon AC, Insel PA, Nicholas RA. Source: Molecular Pharmacology. 2001 December; 60(6): 1375-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11723245&dopt=Abstract
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An expanded glutamine repeat destabilizes native ataxin-3 structure and mediates formation of parallel beta -fibrils. Author(s): Bevivino AE, Loll PJ. Source: Proceedings of the National Academy of Sciences of the United States of America. 2001 October 9; 98(21): 11955-60. Epub 2001 September 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11572942&dopt=Abstract
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Androgen receptor gene polyglutamine length is associated with testicular histology in infertile patients. Author(s): Casella R, Maduro MR, Misfud A, Lipshultz LI, Yong EL, Lamb DJ. Source: The Journal of Urology. 2003 January; 169(1): 224-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478141&dopt=Abstract
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Androgen receptors containing expanded polyglutamine tracts exhibit progressive toxicity when stably expressed in the neuroblastoma cell line, SH-SY 5Y. Author(s): Avila DM, Allman DR, Gallo JM, McPhaul MJ. Source: Experimental Biology and Medicine (Maywood, N.J.). 2003 September; 228(8): 982-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968071&dopt=Abstract
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Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema. Author(s): Picker JD, Puga AC, Levy HL, Marsden D, Shih VE, Degirolami U, Ligon KL, Cederbaum SD, Kern RM, Cox GF. Source: The Journal of Pediatrics. 2003 March; 142(3): 349-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640389&dopt=Abstract
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Assessment of the safety of glutamine and other amino acids. Author(s): Garlick PJ. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2556S-61S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533313&dopt=Abstract
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Association study between CAG trinucleotide repeats in the PCQAP gene (PC2 glutamine/Q-rich-associated protein) and schizophrenia. Author(s): De Luca A, Conti E, Grifone N, Amati F, Spalletta G, Caltagirone C, Bonaviri G, Pasini A, Gennarelli M, Stefano B, Berti L, Mittler G, Meisterernst M, Dallapiccola B, Novelli G. Source: American Journal of Medical Genetics. 2003 January 1; 116B(1): 32-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12497610&dopt=Abstract
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Atypical MELAS syndrome associated with a new mitochondrial tRNA glutamine point mutation. Author(s): Bataillard M, Chatzoglou E, Rumbach L, Sternberg D, Tournade A, Laforet P, Jardel C, Maisonobe T, Lombes A. Source: Neurology. 2001 February 13; 56(3): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11171912&dopt=Abstract
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Basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in vitreous fluid from eyes with retinal detachment complicated by proliferative vitreoretinopathy. Author(s): La Heij EC, van de Waarenburg MP, Blaauwgeers HG, Kessels AG, Liem AT, Theunissen C, Steinbusch H, Hendrikse F. Source: American Journal of Ophthalmology. 2002 September; 134(3): 367-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12208248&dopt=Abstract
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Beyond the Qs in the polyglutamine diseases. Author(s): Orr HT. Source: Genes & Development. 2001 April 15; 15(8): 925-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316786&dopt=Abstract
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Can glutamine and growth hormone promote protein anabolism in children with cystic fibrosis? Author(s): Hayes V, Schaeffer D, Mauras N, Punati J, Darmaun D. Source: Hormone Research. 2002; 58 Suppl 1: 21-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12373009&dopt=Abstract
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Can glutamine modify the apparent immunodepression observed after prolonged, exhaustive exercise? Author(s): Castell LM. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 May; 18(5): 371-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985938&dopt=Abstract
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Cause of neural death in neurodegenerative diseases attributable to expansion of glutamine repeats. Author(s): Perutz MF, Windle AH. Source: Nature. 2001 July 12; 412(6843): 143-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449262&dopt=Abstract
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Changes in the cellular distribution of glutamine synthetase in Alzheimer's disease. Author(s): Robinson SR. Source: Journal of Neuroscience Research. 2001 December 1; 66(5): 972-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746426&dopt=Abstract
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Changes in the nutritional state and immune-serological parameters of esophagectomized patients fed jejunaly with glutamine-poor and glutamine-rich nutriments. Author(s): Hallay J, Kovacs G, Kiss Sz S, Farkas M, Lakos G, Sipka S, Bodolay E, Sapy P. Source: Hepatogastroenterology. 2002 November-December; 49(48): 1555-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397734&dopt=Abstract
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Characteristics of L-glutamine transport during Caco-2 cell differentiation. Author(s): Costa C, Huneau J, Tome D. Source: Biochimica Et Biophysica Acta. 2000 December 20; 1509(1-2): 95-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11118521&dopt=Abstract
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Characterization of L-glutamine transport by a human neuroblastoma cell line. Author(s): Wasa M, Wang HS, Okada A. Source: American Journal of Physiology. Cell Physiology. 2002 June; 282(6): C1246-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997238&dopt=Abstract
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Clinical evidence for enteral nutritional support with glutamine: a systematic review. Author(s): Garcia-de-Lorenzo A, Zarazaga A, Garcia-Luna PP, Gonzalez-Huix F, LopezMartinez J, Mijan A, Quecedo L, Casimiro C, Usan L, del Llano J. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 September; 19(9): 805-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12921894&dopt=Abstract
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Cloning and characterization of mouse glutamine:fructose-6-phosphate amidotransferase 2 gene promoter. Author(s): Yamazaki K, Mizui Y, Oki T, Okada M, Tanaka I. Source: Gene. 2000 December 31; 261(2): 329-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11167021&dopt=Abstract
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Combination of recombinant human growth hormone and glutamine-enriched total parenteral nutrition to surgical patients: effects on circulating amino acids. Author(s): Kolstad O, Jenssen TG, Ingebretsen OC, Vinnars E, Revhaug A. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 December; 20(6): 503-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11883998&dopt=Abstract
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Combined growth hormone/insulin-like growth factor I in addition to glutaminesupplemented TPN results in net protein anabolism in critical illness. Author(s): Carroll PV, Jackson NC, Russell-Jones DL, Treacher DF, Sonksen PH, Umpleby AM. Source: American Journal of Physiology. Endocrinology and Metabolism. 2004 January; 286(1): E151-7. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759221&dopt=Abstract
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Comparison of a immunonutrition formula enriched arginine, glutamine and omega3 fatty acid, with a currently high-enriched enteral nutrition for trauma patients. Author(s): Chuntrasakul C, Siltham S, Sarasombath S, Sittapairochana C, Leowattana W, Chockvivatanavanit S, Bunnak A. Source: J Med Assoc Thai. 2003 June; 86(6): 552-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924804&dopt=Abstract
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Compartmentation of glutamine, glutamate, and GABA metabolism in neurons and astrocytes: functional implications. Author(s): Waagepetersen HS, Sonnewald U, Schousboe A. Source: The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry. 2003 October; 9(5): 398-403. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14580123&dopt=Abstract
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Conditionally indispensable amino acids (glutamine, cyst(e)ine, tyrosine, arginine, ornithine, taurine) in enteral feeding and the dipeptide concept. Author(s): Furst P. Source: Nestle Nutr Workshop Ser Clin Perform Programme. 2000; 3: 199-217; Discussion 217-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490607&dopt=Abstract
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Continuous and intermittent exposure to the hypoxia of altitude: implications for glutamine metabolism and exercise performance. Author(s): Bailey DM, Castell LM, Newsholme EA, Davies B. Source: British Journal of Sports Medicine. 2000 June; 34(3): 210-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10854022&dopt=Abstract
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Contribution of a thickened cell wall and its glutamine nonamidated component to the vancomycin resistance expressed by Staphylococcus aureus Mu50. Author(s): Cui L, Murakami H, Kuwahara-Arai K, Hanaki H, Hiramatsu K. Source: Antimicrobial Agents and Chemotherapy. 2000 September; 44(9): 2276-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952568&dopt=Abstract
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Cost-containment with glutamine dipeptide-supplemented TPN. Author(s): Sitges-Serra A. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 June; 20(3): 285-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407879&dopt=Abstract
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Decreased glutamate + glutamine in Alzheimer's disease detected in vivo with (1)HMRS at 0.5 T. Author(s): Antuono PG, Jones JL, Wang Y, Li SJ. Source: Neurology. 2001 March 27; 56(6): 737-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11274307&dopt=Abstract
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Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Author(s): Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D'Elia M, Bernier J. Source: Critical Care Medicine. 2003 October; 31(10): 2444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530749&dopt=Abstract
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Decreased plasma and cerebrospinal fluid glutamine concentrations in a patient with bialaphos poisoning. Author(s): Ohtake T, Yasuda H, Takahashi H, Goto T, Suzuki K, Yonemura K, Hishida A. Source: Human & Experimental Toxicology. 2001 August; 20(8): 429-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11727795&dopt=Abstract
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Deficiency in peripheral glutamine production in pediatric patients with burns. Author(s): Gore DC, Jahoor F. Source: The Journal of Burn Care & Rehabilitation. 2000 March-April; 21(2): 171; Discussion 172-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10752751&dopt=Abstract
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Development of a bioartificial liver with glutamine synthetase-transduced recombinant human hepatoblastoma cell line, HepG2. Author(s): Miyashita T, Enosawa S, Suzuki S, Tamura A, Tanaka H, Amemiya H, Matsumura T, Omasa T, Suga K, Aoki T, Koyanagi Y. Source: Transplantation Proceedings. 2000 November; 32(7): 2355-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120198&dopt=Abstract
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Does glutamine enable severely ill intensive care patients to cope better with infection and increase their chance of survival? Author(s): Hardy G. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 September; 18(9): 712-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297200&dopt=Abstract
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Dysregulatory dysequilibrium of gene transcription and of nuclear transport in polyglutamine neuro-degeneration. Author(s): Agius LM. Source: Medical Hypotheses. 2003 June; 60(6): 869-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12699716&dopt=Abstract
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Early endosomal localization of hrs requires a sequence within the proline- and glutamine-rich region but not the FYVE finger. Author(s): Hayakawa A, Kitamura N. Source: The Journal of Biological Chemistry. 2000 September 22; 275(38): 29636-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10889197&dopt=Abstract
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Effect of a glutamine-enriched enteral diet on intestinal permeability and infectious morbidity at 28 days in critically ill patients with systemic inflammatory response syndrome: a randomized, single-blind, prospective, multicenter study. Author(s): Conejero R, Bonet A, Grau T, Esteban A, Mesejo A, Montejo JC, Lopez J, Acosta JA. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 September; 18(9): 716-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297203&dopt=Abstract
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Effect of a short CAG (glutamine) repeat on human androgen receptor function. Author(s): Ding D, Xu L, Menon M, Reddy GP, Barrack ER. Source: The Prostate. 2004 January 1; 58(1): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14673949&dopt=Abstract
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Effect of blood ammonia elevation following oral glutamine load on the psychometric performance of cirrhotic patients. Author(s): Masini A, Efrati C, Merli M, Nicolao F, Amodio P, Del Piccolo F, Riggio O. Source: Metabolic Brain Disease. 2003 March; 18(1): 27-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603080&dopt=Abstract
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Effect of enteral glutamine on leucine, phenylalanine and glutamine metabolism in hypercortisolemic subjects. Author(s): Claeyssens S, Bouteloup-Demange C, Gachon P, Hecketsweiler B, Lerebours E, Lavoinne A, Dechelotte P. Source: American Journal of Physiology. Endocrinology and Metabolism. 2000 May; 278(5): E817-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10780937&dopt=Abstract
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Effect of enteral supplementation with glutamine on mesenteric blood flow in premature neonates. Author(s): Mercier A, Eurin D, Poulet-Young V, Marret S, Dechelotte P. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 April; 22(2): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706129&dopt=Abstract
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Effect of glutamine and protein supplementation on exercise-induced decreases in salivary IgA. Author(s): Krzywkowski K, Petersen EW, Ostrowski K, Link-Amster H, Boza J, Halkjaer-Kristensen J, Pedersen BK. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 August; 91(2): 832-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11457800&dopt=Abstract
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Effect of glutamine in short-bowel syndrome. Author(s): Scolapio JS, McGreevy K, Tennyson GS, Burnett OL. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 August; 20(4): 319-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11478829&dopt=Abstract
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Effect of glutamine supplementation combined with resistance training in young adults. Author(s): Candow DG, Chilibeck PD, Burke DG, Davison KS, Smith-Palmer T. Source: European Journal of Applied Physiology. 2001 December; 86(2): 142-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11822473&dopt=Abstract
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Effect of glutamine supplementation on exercise-induced changes in lymphocyte function. Author(s): Krzywkowski K, Petersen EW, Ostrowski K, Kristensen JH, Boza J, Pedersen BK. Source: American Journal of Physiology. Cell Physiology. 2001 October; 281(4): C125965. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11546663&dopt=Abstract
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Effect of glutamine-enriched total parenteral nutrition in patients with acute pancreatitis. Author(s): Ockenga J, Borchert K, Rifai K, Manns MP, Bischoff SC. Source: Clinical Nutrition (Edinburgh, Lothian). 2002 October; 21(5): 409-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381339&dopt=Abstract
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Effect of growth hormone and glutamine on the short bowel: five years later. Author(s): Scolapio JS. Source: Gut. 2000 August; 47(2): 164. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896902&dopt=Abstract
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Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study. Author(s): Szkudlarek J, Jeppesen PB, Mortensen PB. Source: Gut. 2000 August; 47(2): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896910&dopt=Abstract
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Effect of high-dose growth hormone and glutamine on body composition, urine creatinine excretion, fatty acid absorption, and essential fatty acids status in short bowel patients: a randomized, double-blind, crossover, placebo-controlled study. Author(s): Jeppesen PB, Szkudlarek J, Hoy CE, Mortensen PB. Source: Scandinavian Journal of Gastroenterology. 2001 January; 36(1): 48-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218239&dopt=Abstract
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Effect of L-ornithine-L-aspartate on patients with and without TIPS undergoing glutamine challenge: a double blind, placebo controlled trial. Author(s): Rees CJ, Oppong K, Al Mardini H, Hudson M, Record CO. Source: Gut. 2000 October; 47(4): 571-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10986219&dopt=Abstract
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Effect of oral glutamine supplementation during bone marrow transplantation. Author(s): Coghlin Dickson TM, Wong RM, offrin RS, Shizuru JA, Johnston LJ, Hu WW, Blume KG, Stockerl-Goldstein KE. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 March-April; 24(2): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772184&dopt=Abstract
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Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants. Author(s): Poindexter BB, Ehrenkranz RA, Stoll BJ, Koch MA, Wright LL, Oh W, Papile LA, Bauer CR, Carlo WA, Donovan EF, Fanaroff AA, Korones SB, Laptook AR, Shankaran S, Stevenson DK, Tyson JE, Lemons JA; National Institute of Child Health and Human Development Neonatal Research Network. Source: The American Journal of Clinical Nutrition. 2003 March; 77(3): 737-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12600870&dopt=Abstract
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Effect of replacing the aspartic acid/glutamic acid residues of bullfrog sialic acid binding lectin with asparagine/glutamine and arginine on the inhibition of cell proliferation in murine leukemia P388 cells. Author(s): Ogawa Y, Iwama M, Ohgi K, Tsuji T, Irie M, Itagaki T, Kobayashi H, Inokuchi N. Source: Biological & Pharmaceutical Bulletin. 2002 June; 25(6): 722-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081136&dopt=Abstract
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Effect of sodium benzoate on blood ammonia response to oral glutamine challenge in cirrhotic patients: a note of caution. Author(s): Efrati C, Masini A, Merli M, Valeriano V, Riggio O. Source: The American Journal of Gastroenterology. 2000 December; 95(12): 3574-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151894&dopt=Abstract
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Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Author(s): Pfleiderer B, Michael N, Erfurth A, Ohrmann P, Hohmann U, Wolgast M, Fiebich M, Arolt V, Heindel W. Source: Psychiatry Research. 2003 April 1; 122(3): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12694892&dopt=Abstract
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Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects. Author(s): Arwert LI, Deijen JB, Drent ML. Source: Nutritional Neuroscience. 2003 October; 6(5): 269-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14609312&dopt=Abstract
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Effects of arginine, L-alanyl-L-glutamine or taurine on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Author(s): Muhling J, Fuchs M, Fleck C, Sablotzki A, Krull M, Dehne MG, Gonter J, Weiss S, Engel J, Hempelmann G. Source: Amino Acids. 2002; 22(1): 39-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025873&dopt=Abstract
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Effects of enteral glutamine on gut mucosal protein synthesis in healthy humans receiving glucocorticoids. Author(s): Bouteloup-Demange C, Claeyssens S, Maillot C, Lavoinne A, Lerebours E, Dechelotte P. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2000 May; 278(5): G677-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10801259&dopt=Abstract
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Effects of glutamine deprivation on protein synthesis in a model of human enterocytes in culture. Author(s): Le Bacquer O, Nazih H, Blottiere H, Meynial-Denis D, Laboisse C, Darmaun D. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2001 December; 281(6): G1340-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705738&dopt=Abstract
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Effects of glutamine isomers on human (Caco-2) intestinal epithelial proliferation, strain-responsiveness, and differentiation. Author(s): Murnin M, Kumar A, Li GD, Brown M, Sumpio BE, Basson MD. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2000 July-August; 4(4): 435-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11058864&dopt=Abstract
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Effects of glutamine on tumor growth and apoptosis of hepatoma cells. Author(s): Liu SL, Shi DY, Shen ZH, Wu YD. Source: Acta Pharmacologica Sinica. 2000 July; 21(7): 668-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11360680&dopt=Abstract
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Effects of oral supplement of L-glutamine on diverted colon wall. Author(s): Paulo FL. Source: Journal of Cellular and Molecular Medicine. 2002 July-September; 6(3): 377-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417053&dopt=Abstract
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Enteral glutamine stimulates protein synthesis and decreases ubiquitin mRNA level in human gut mucosa. Author(s): Coeffier M, Claeyssens S, Hecketsweiler B, Lavoinne A, Ducrotte P, Dechelotte P. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2003 August; 285(2): G266-73. Epub 2003 April 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702496&dopt=Abstract
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Enteral glutamine supplementation and morbidity in low birth weight infants. Author(s): Vaughn P, Thomas P, Clark R, Neu J. Source: The Journal of Pediatrics. 2003 June; 142(6): 662-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838195&dopt=Abstract
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Epidermal growth factor activation of intestinal glutamine transport is mediated by mitogen-activated protein kinases. Author(s): Wolfgang CL, Lin C, Meng Q, Karinch AM, Vary TC, Pan M. Source: Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract. 2003 January; 7(1): 149-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12559196&dopt=Abstract
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Exercise-induced immunodepression- plasma glutamine is not the link. Author(s): Hiscock N, Pedersen BK. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2002 September; 93(3): 813-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12183472&dopt=Abstract
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Expression of full-length polyglutamine-expanded Huntingtin disrupts growth factor receptor signaling in rat pheochromocytoma (PC12) cells. Author(s): Song C, Perides G, Liu YF. Source: The Journal of Biological Chemistry. 2002 February 22; 277(8): 6703-7. Epub 2001 December 03. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11733534&dopt=Abstract
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Free and protein-bound glutamine have identical splanchnic extraction in healthy human volunteers. Author(s): Boza JJ, Dangin M, Moennoz D, Montigon F, Vuichoud J, Jarret A, Pouteau E, Gremaud G, Oguey-Araymon S, Courtois D, Woupeyi A, Finot PA, Ballevre O. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2001 July; 281(1): G267-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11408280&dopt=Abstract
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Free glutamine and glutamic acid increase in human milk through a three-month lactation period. Author(s): Agostoni C, Carratu B, Boniglia C, Lammardo AM, Riva E, Sanzini E. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 November; 31(5): 50812. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144435&dopt=Abstract
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Full-sized RanBPM cDNA encodes a protein possessing a long stretch of proline and glutamine within the N-terminal region, comprising a large protein complex. Author(s): Nishitani H, Hirose E, Uchimura Y, Nakamura M, Umeda M, Nishii K, Mori N, Nishimoto T. Source: Gene. 2001 July 11; 272(1-2): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470507&dopt=Abstract
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Functional integration of the transport of ammonium, glutamate and glutamine in astrocytes. Author(s): Brookes N. Source: Neurochemistry International. 2000 August-September; 37(2-3): 121-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10812197&dopt=Abstract
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Functional mapping of the GAGA factor assigns its transcriptional activity to the Cterminal glutamine-rich domain. Author(s): Vaquero A, Espinas ML, Azorin F, Bernues J. Source: The Journal of Biological Chemistry. 2000 June 30; 275(26): 19461-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764754&dopt=Abstract
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Further evidence for the beneficial effects of glutamine in the nutrition of ICU patients. Author(s): Wernerman J. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 September; 18(9): 722. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297204&dopt=Abstract
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Glucocorticoid induced expression of glutamine synthetase in hepatoma cells. Author(s): Gaunitz F, Heise K, Schumann R, Gebhardt R. Source: Biochemical and Biophysical Research Communications. 2002 August 30; 296(4): 1026-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200152&dopt=Abstract
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Glucose, but not glutamine, protects against spontaneous and anti-Fas antibodyinduced apoptosis in human neutrophils. Author(s): Healy DA, Watson RW, Newsholme P. Source: Clinical Science (London, England : 1979). 2002 August; 103(2): 179-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149110&dopt=Abstract
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Glutamate and glutamine in the anterior cingulate and thalamus of medicated patients with chronic schizophrenia and healthy comparison subjects measured with 4.0-T proton MRS. Author(s): Theberge J, Al-Semaan Y, Williamson PC, Menon RS, Neufeld RW, Rajakumar N, Schaefer B, Densmore M, Drost DJ. Source: The American Journal of Psychiatry. 2003 December; 160(12): 2231-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14638596&dopt=Abstract
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Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Author(s): Theberge J, Bartha R, Drost DJ, Menon RS, Malla A, Takhar J, Neufeld RW, Rogers J, Pavlosky W, Schaefer B, Densmore M, Al-Semaan Y, Williamson PC. Source: The American Journal of Psychiatry. 2002 November; 159(11): 1944-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12411236&dopt=Abstract
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Glutamate-glutamine cycling in the epileptic human hippocampus. Author(s): Petroff OA, Errante LD, Rothman DL, Kim JH, Spencer DD. Source: Epilepsia. 2002 July; 43(7): 703-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12102672&dopt=Abstract
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Glutamine and acute illness. Author(s): Wernerman J. Source: Current Opinion in Critical Care. 2003 August; 9(4): 279-85. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12883282&dopt=Abstract
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Glutamine and arginine affect Caco-2 cell proliferation by promotion of nucleotide synthesis. Author(s): Yamauchi K, Komatsu T, Kulkarni AD, Ohmori Y, Minami H, Ushiyama Y, Nakayama M, Yamamoto S. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 April; 18(4): 329-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934546&dopt=Abstract
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Glutamine and barrier function in cultured Caco-2 epithelial cell monolayers. Author(s): DeMarco VG, Li N, Thomas J, West CM, Neu J. Source: The Journal of Nutrition. 2003 July; 133(7): 2176-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12840174&dopt=Abstract
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Glutamine and glutamate as vital metabolites. Author(s): Newsholme P, Lima MM, Procopio J, Pithon-Curi TC, Doi SQ, Bazotte RB, Curi R. Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2003 February; 36(2): 153-63. Epub 2003 January 29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563517&dopt=Abstract
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Glutamine and glutamate--their central role in cell metabolism and function. Author(s): Newsholme P, Procopio J, Lima MM, Pithon-Curi TC, Curi R. Source: Cell Biochemistry and Function. 2003 March; 21(1): 1-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12579515&dopt=Abstract
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Glutamine and gut barrier function. Author(s): MacFie J, McNaught C. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 May; 18(5): 433-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985953&dopt=Abstract
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Glutamine and its relationship with intracellular redox status, oxidative stress and cell proliferation/death. Author(s): Mates JM, Perez-Gomez C, Nunez de Castro I, Asenjo M, Marquez J. Source: The International Journal of Biochemistry & Cell Biology. 2002 May; 34(5): 43958. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11906817&dopt=Abstract
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Glutamine and KGF each regulate extracellular thiol/disulfide redox and enhance proliferation in Caco-2 cells. Author(s): Jonas CR, Gu LH, Nkabyo YS, Mannery YO, Avissar NE, Sax HC, Jones DP, Ziegler TR. Source: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2003 December; 285(6): R1421-9. Epub 2003 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12947032&dopt=Abstract
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Glutamine and wound healing. Author(s): Collins N. Source: Advances in Skin & Wound Care. 2002 September-October; 15(5): 233-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368714&dopt=Abstract
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Glutamine attenuates post-traumatic glutathione depletion in human muscle. Author(s): Flaring UB, Rooyackers OE, Wernerman J, Hammarqvist F. Source: Clinical Science (London, England : 1979). 2003 March; 104(3): 275-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12605586&dopt=Abstract
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Glutamine attenuates tumor necrosis factor-alpha release and enhances heat shock protein 72 in human peripheral blood mononuclear cells. Author(s): Wischmeyer PE, Riehm J, Singleton KD, Ren H, Musch MW, Kahana M, Chang EB. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 January; 19(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507630&dopt=Abstract
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Glutamine decreases interleukin-8 and interleukin-6 but not nitric oxide and prostaglandins e(2) production by human gut in-vitro. Author(s): Coeffier M, Marion R, Leplingard A, Lerebours E, Ducrotte P, Dechelotte P. Source: Cytokine. 2002 April 21; 18(2): 92-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12096924&dopt=Abstract
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Glutamine delays spontaneous apoptosis in neutrophils. Author(s): Pithon-Curi TC, Schumacher RI, Freitas JJ, Lagranha C, Newsholme P, Palanch AC, Doi SQ, Curi R. Source: American Journal of Physiology. Cell Physiology. 2003 June; 284(6): C1355-61. Epub 2003 January 15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529242&dopt=Abstract
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Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate. Author(s): Clark EC, Patel SD, Chadwick PR, Warhurst G, Curry A, Carlson GL. Source: Gut. 2003 February; 52(2): 224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524404&dopt=Abstract
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Glutamine distribution in patients with ulcerative colitis and in patients with familial adenomatous polyposis coli before and after restorative proctocolectomy. Author(s): Heuschen UA, Allemeyer EH, Hinz U, Langer K, Heuschen G, DeckerBaumann C, Herfarth C, Stern J. Source: International Journal of Colorectal Disease. 2002 July; 17(4): 245-52. Epub 2001 December 18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12073073&dopt=Abstract
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Glutamine for short-bowel syndrome. Author(s): Buchman AL. Source: Current Gastroenterology Reports. 2002 August; 4(4): 321. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12149172&dopt=Abstract
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Glutamine in pediatrics: where next? Author(s): Ball PA, Hardy G. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 June; 18(6): 451-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044814&dopt=Abstract
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Glutamine metabolism in the fetus and critically ill low birth weight neonate. Author(s): Neu J, Auestad N, DeMarco VG. Source: Adv Pediatr. 2002; 49: 203-26. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214772&dopt=Abstract
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Glutamine preserves protein synthesis and paracellular permeability in Caco-2 cells submitted to “luminal fasting”. Author(s): Le Bacquer O, Laboisse C, Darmaun D. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2003 July; 285(1): G128-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12799310&dopt=Abstract
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Glutamine prevents cytokine-induced apoptosis in human colonic epithelial cells. Author(s): Evans ME, Jones DP, Ziegler TR. Source: The Journal of Nutrition. 2003 October; 133(10): 3065-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14519785&dopt=Abstract
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Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. Author(s): Chang WK, Yang KD, Chuang H, Jan JT, Shaio MF. Source: Clinical Immunology (Orlando, Fla.). 2002 August; 104(2): 151-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12165276&dopt=Abstract
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Glutamine repeats: structural hypotheses and neurodegeneration. Author(s): Masino L, Pastore A. Source: Biochemical Society Transactions. 2002 August; 30(4): 548-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12196134&dopt=Abstract
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Glutamine starvation of monocytes inhibits the ubiquitin-proteasome proteolytic pathway. Author(s): Zellner M, Gerner C, Munk Eliasen M, Wurm S, Pollheimer J, Spittler A, Brostjan C, Roth E, Oehler R. Source: Biochimica Et Biophysica Acta. 2003 July 14; 1638(2): 138-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12853119&dopt=Abstract
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Glutamine stimulates argininosuccinate synthetase gene expression through cytosolic O-glycosylation of Sp1 in Caco-2 cells. Author(s): Brasse-Lagnel C, Fairand A, Lavoinne A, Husson A. Source: The Journal of Biological Chemistry. 2003 December 26; 278(52): 52504-10. Epub 2003 October 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570901&dopt=Abstract
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Glutamine supplementation and deprivation: effect on artificially reared rat small intestinal morphology. Author(s): Potsic B, Holliday N, Lewis P, Samuelson D, DeMarco V, Neu J. Source: Pediatric Research. 2002 September; 52(3): 430-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193680&dopt=Abstract
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Glutamine supplementation fails to affect muscle protein kinetics in critically ill patients. Author(s): Gore DC, Wolfe RR. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2002 November-December; 26(6): 342-9; Discussion 349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405645&dopt=Abstract
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Glutamine supplementation further enhances exercise-induced plasma IL-6. Author(s): Hiscock N, Petersen EW, Krzywkowski K, Boza J, Halkjaer-Kristensen J, Pedersen BK. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 July; 95(1): 145-8. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611772&dopt=Abstract
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Glutamine supplementation in bone marrow transplantation. Author(s): Ziegler TR. Source: The British Journal of Nutrition. 2002 January; 87 Suppl 1: S9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895159&dopt=Abstract
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Glutamine supplementation in critically ill and elective surgical patients: does the evidence warrant its use? Author(s): Miskovitz P. Source: Critical Care Medicine. 2002 September; 30(9): 2152-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352061&dopt=Abstract
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Glutamine supplementation in serious illness: a systematic review of the evidence. Author(s): Novak F, Heyland DK, Avenell A, Drover JW, Su X. Source: Critical Care Medicine. 2002 September; 30(9): 2022-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352035&dopt=Abstract
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Glutamine supplementation in vitro and in vivo, in exercise and in immunodepression. Author(s): Castell L. Source: Sports Medicine (Auckland, N.Z.). 2003; 33(5): 323-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696982&dopt=Abstract
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Glutamine supplements in premature infants: why and how. Author(s): Neu J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 5335. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581791&dopt=Abstract
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Glutamine supports recovery from loss of transepithelial resistance and increase of permeability induced by media change in Caco-2 cells. Author(s): Li N, DeMarco VG, West CM, Neu J. Source: The Journal of Nutritional Biochemistry. 2003 July; 14(7): 401-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12915221&dopt=Abstract
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Glutamine synthetase and glutamate dehydrogenase in the prefrontal cortex of patients with schizophrenia. Author(s): Burbaeva GSh, Boksha IS, Turishcheva MS, Vorobyeva EA, Savushkina OK, Tereshkina EB. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 June; 27(4): 675-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787856&dopt=Abstract
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Glutamine synthetase GlnA1 is essential for growth of Mycobacterium tuberculosis in human THP-1 macrophages and guinea pigs. Author(s): Tullius MV, Harth G, Horwitz MA. Source: Infection and Immunity. 2003 July; 71(7): 3927-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12819079&dopt=Abstract
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Glutamine synthetase in brain: effect of ammonia. Author(s): Suarez I, Bodega G, Fernandez B. Source: Neurochemistry International. 2002 August-September; 41(2-3): 123-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12020613&dopt=Abstract
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Glutamine synthetase isolated from human brain: octameric structure and homology of partial primary structure with human liver glutamine synthetase. Author(s): Boksha IS, Schonfeld HJ, Langen H, Muller F, Tereshkina EB, Burbaeva GSh. Source: Biochemistry. Biokhimiia. 2002 September; 67(9): 1012-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12387715&dopt=Abstract
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Glutamine to intensive care unit patients. Author(s): Wernerman J. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 July-August; 27(4): 302-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903897&dopt=Abstract
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Glutamine, a life-saving nutrient, but why? Author(s): Preiser JC, Wernerman J. Source: Critical Care Medicine. 2003 October; 31(10): 2555-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530768&dopt=Abstract
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Glutamine-enhanced nutrition in the critically ill patient. Author(s): Andrews F, Griffiths R. Source: Hosp Med. 2002 March; 63(3): 144-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933816&dopt=Abstract
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Glutamine-enriched enteral nutrition decreases infectious complications in trauma patients. Author(s): Boelens PG, Houdijk AP, Haarman HJ, Nijveldt RJ, van Leeuwen PA. Source: The American Journal of Clinical Nutrition. 2002 July; 76(1): 253-4; Author Reply 254-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12081843&dopt=Abstract
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Glutamine-enriched enteral nutrition increases HLA-DR expression on monocytes of trauma patients. Author(s): Boelens PG, Houdijk AP, Fonk JC, Nijveldt RJ, Ferwerda CC, Von BlombergVan Der Flier BM, Thijs LG, Haarman HJ, Puyana JC, Van Leeuwen PA. Source: The Journal of Nutrition. 2002 September; 132(9): 2580-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221212&dopt=Abstract
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Glutamine-enriched parenteral nutrition after autologous peripheral blood stem cell transplantation: effects on immune reconstitution and mucositis. Author(s): Piccirillo N, De Matteis S, Laurenti L, Chiusolo P, Sora F, Pittiruti M, Rutella S, Cicconi S, Fiorini A, D'Onofrio G, Leone G, Sica S. Source: Haematologica. 2003 February; 88(2): 192-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604409&dopt=Abstract
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Hepatic glutamine metabolism. Author(s): Watford M, Chellaraj V, Ismat A, Brown P, Raman P. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 April; 18(4): 301-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11934540&dopt=Abstract
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Histone H3 is aberrantly phosphorylated in glutamine-repeat diseases. Author(s): Yazawa I, Hazeki N, Nakase H, Kanazawa I, Tanaka M. Source: Biochemical and Biophysical Research Communications. 2003 February 28; 302(1): 144-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593861&dopt=Abstract
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Human 293 cell metabolism in low glutamine-supplied culture: interpretation of metabolic changes through metabolic flux analysis. Author(s): Nadeau I, Sabatie J, Koehl M, Perrier M, Kamen A. Source: Metabolic Engineering. 2000 October; 2(4): 277-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120640&dopt=Abstract
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Huntingtin inclusions do not deplete polyglutamine-containing transcription factors in HD mice. Author(s): Yu ZX, Li SH, Nguyen HP, Li XJ. Source: Human Molecular Genetics. 2002 April 15; 11(8): 905-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971872&dopt=Abstract
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Identification of a cis-acting element and a novel trans-acting factor of the glutamine synthetase gene in liver cells. Author(s): Gaunitz F, Weber S, Scheja L, Gebhardt R. Source: Biochemical and Biophysical Research Communications. 2001 June 8; 284(2): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11394889&dopt=Abstract
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Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay. Author(s): Heiser V, Engemann S, Brocker W, Dunkel I, Boeddrich A, Waelter S, Nordhoff E, Lurz R, Schugardt N, Rautenberg S, Herhaus C, Barnickel G, Bottcher H, Lehrach H, Wanker EE. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 December 10; 99 Suppl 4: 16400-6. Epub 2002 August 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200548&dopt=Abstract
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Identification of GFAT1-L, a novel splice variant of human glutamine: fructose-6phosphate amidotransferase (GFAT1) that is expressed abundantly in skeletal muscle. Author(s): Niimi M, Ogawara T, Yamashita T, Yamamoto Y, Ueyama A, Kambe T, Okamoto T, Ban T, Tamanoi H, Ozaki K, Fujiwara T, Fukui H, Takahashi EI, Kyushiki H, Tanigami A. Source: Journal of Human Genetics. 2001; 46(10): 566-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11587069&dopt=Abstract
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Identification of phenylbutyrylglutamine, a new metabolite of phenylbutyrate metabolism in humans. Author(s): Comte B, Kasumov T, Pierce BA, Puchowicz MA, Scott ME, Dahms W, Kerr D, Nissim I, Brunengraber H. Source: Journal of Mass Spectrometry : Jms. 2002 June; 37(6): 581-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12112740&dopt=Abstract
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II. Glutamine and glutamate. Author(s): Tapiero H, Mathe G, Couvreur P, Tew KD. Source: Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. 2002 November; 56(9): 446-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12481981&dopt=Abstract
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Immunoassay for serum glutamine synthetase in serum: development, reference values, and preliminary study in dementias. Author(s): Takahashi M, Stanton E, Moreno JI, Jackowski G. Source: Clinical Chemistry. 2002 February; 48(2): 375-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805026&dopt=Abstract
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Impact of oral L-glutamine on glutathione, glutamine, and glutamate blood levels in volunteers. Author(s): Valencia E, Marin A, Hardy G. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 May; 18(5): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985937&dopt=Abstract
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Impaired energy metabolism during neonatal sepsis: the effects of glutamine. Author(s): Eaton S. Source: The Proceedings of the Nutrition Society. 2003 August; 62(3): 745-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14692610&dopt=Abstract
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Impaired glutamate transport and glutamate-glutamine cycling: downstream effects of the Huntington mutation. Author(s): Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB. Source: Brain; a Journal of Neurology. 2002 August; 125(Pt 8): 1908-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135980&dopt=Abstract
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Improved fermentation processes for NS0 cell lines expressing human antibodies and glutamine synthetase. Author(s): Dempsey J, Ruddock S, Osborne M, Ridley A, Sturt S, Field R. Source: Biotechnology Progress. 2003 January-February; 19(1): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573022&dopt=Abstract
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Improving glucose and glutamine metabolism of human HEK 293 and Trichoplusia ni insect cells engineered to express a cytosolic pyruvate carboxylase enzyme. Author(s): Elias CB, Carpentier E, Durocher Y, Bisson L, Wagner R, Kamen A. Source: Biotechnology Progress. 2003 January-February; 19(1): 90-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12573011&dopt=Abstract
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Improving nutritional support in critically Ill septic patients: glutamine alone or in combination? Author(s): Chiolero RL, Berger MM. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 September; 18(9): 723-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12297205&dopt=Abstract
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In vivo measurements of glutamine + glutamate (Glx) and N-acetyl aspartate (NAA) levels in human partial epilepsy. Author(s): Savic I, Thomas AM, Ke Y, Curran J, Fried I, Engel J Jr. Source: Acta Neurologica Scandinavica. 2000 September; 102(3): 179-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10987378&dopt=Abstract
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In vivo nuclear magnetic resonance studies of glutamate-gamma-aminobutyric acidglutamine cycling in rodent and human cortex: the central role of glutamine. Author(s): Behar KL, Rothman DL. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2498S-504S; Discussion 2523S-4S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533301&dopt=Abstract
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Infection, multiple organ failure, and survival in the intensive care unit: influence of glutamine-supplemented parenteral nutrition on acquired infection. Author(s): Griffiths RD, Allen KD, Andrews FJ, Jones C. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 July-August; 18(7-8): 54652. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093428&dopt=Abstract
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Influence of glutamine and glycyl-glutamine on in vitro lymphocyte proliferation in children with solid tumors. Author(s): Kohler H, Klowik M, Brand O, Gobel U, Schroten H. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2001 June; 9(4): 261-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430422&dopt=Abstract
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Influence of glutamine on cytokine production by human gut in vitro. Author(s): Coeffier M, Miralles-Barrachina O, Le Pessot F, Lalaude O, Daveau M, Lavoinne A, Lerebours E, Dechelotte P. Source: Cytokine. 2001 February 7; 13(3): 148-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161457&dopt=Abstract
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Influence of glutamine-enriched parenteral nutrition on nitrogen balance and immunologic status in patients undergoing elective aortic aneurysm repair. Author(s): Karwowska KA, Dworacki G, Trybus M, Zeromski J, Szulc R. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 June; 17(6): 475-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399407&dopt=Abstract
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Influence of glutamine-supplemented Caco-2 cells on cytokine production of mononuclear cells. Author(s): Aosasa S, Wells-Byrum D, Alexander JW, Ogle CK. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 September-October; 27(5): 333-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971733&dopt=Abstract
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Influence of polymeric enteral nutrition supplemented with different doses of glutamine on gut permeability in critically ill patients. Author(s): Velasco N, Hernandez G, Wainstein C, Castillo L, Maiz A, Lopez F, Guzman S, Bugedo G, Acosta AM, Bruhn A. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 November-December; 17(11-12): 907-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11744338&dopt=Abstract
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Inhibition of glutamine synthetase in a549 cells during hyperoxia. Author(s): McGrath-Morrow SA, Stahl J. Source: American Journal of Respiratory Cell and Molecular Biology. 2002 July; 27(1): 99-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091252&dopt=Abstract
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Inhibition of glutamine transport depletes glutamate and GABA neurotransmitter pools: further evidence for metabolic compartmentation. Author(s): Rae C, Hare N, Bubb WA, McEwan SR, Broer A, McQuillan JA, Balcar VJ, Conigrave AD, Broer S. Source: Journal of Neurochemistry. 2003 April; 85(2): 503-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675927&dopt=Abstract
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Inhibition of muscle glutamine formation in hypercatabolic patients. Author(s): Biolo G, Fleming RY, Maggi SP, Nguyen TT, Herndon DN, Wolfe RR. Source: Clinical Science (London, England : 1979). 2000 September; 99(3): 189-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11787470&dopt=Abstract
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Inhibition of Mycobacterium tuberculosis glutamine synthetase as a novel antibiotic strategy against tuberculosis: demonstration of efficacy in vivo. Author(s): Harth G, Horwitz MA. Source: Infection and Immunity. 2003 January; 71(1): 456-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12496196&dopt=Abstract
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Insulin-like growth factor-I stimulates amino acid transport in a glutamine-deprived human neuroblastoma cell line. Author(s): Wasa M, Wang HS, Tazuke Y, Okada A. Source: Biochimica Et Biophysica Acta. 2001 February 16; 1525(1-2): 118-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11342260&dopt=Abstract
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Interaction between glutamine availability and metabolism of glycogen, tricarboxylic acid cycle intermediates and glutathione. Author(s): Rennie MJ, Bowtell JL, Bruce M, Khogali SE. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2488S-90S; Discussion 2496S-7S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533298&dopt=Abstract
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Intravenous glutamine does not stimulate mixed muscle protein synthesis in healthy young men and women. Author(s): Zachwieja JJ, Witt TL, Yarasheski KE. Source: Metabolism: Clinical and Experimental. 2000 December; 49(12): 1555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11145116&dopt=Abstract
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Is glutamine beneficial in ischemic heart disease? Author(s): Khogali SE, Pringle SD, Weryk BV, Rennie MJ. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 February; 18(2): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844641&dopt=Abstract
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Is there a requirement for glutamine catabolism in the small intestine? Author(s): Watford M. Source: The British Journal of Nutrition. 1999 April; 81(4): 261-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10999012&dopt=Abstract
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John M. Kinney International Awards. Looking back: a human reason for studying the effects of glutamine in patients with AIDS. Author(s): Shabert JK. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 March; 17(3): 205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11312061&dopt=Abstract
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Kinetic characterization of human glutamine-fructose-6-phosphate amidotransferase I: potent feedback inhibition by glucosamine 6-phosphate. Author(s): Broschat KO, Gorka C, Page JD, Martin-Berger CL, Davies MS, Huang Hc HC, Gulve EA, Salsgiver WJ, Kasten TP. Source: The Journal of Biological Chemistry. 2002 April 26; 277(17): 14764-70. Epub 2002 February 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11842094&dopt=Abstract
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Levels of basic fibroblast growth factor, glutamine synthetase, and interleukin-6 in subretinal fluid from patients with retinal detachment. Author(s): La Heij EC, Van De Waarenburg MP, Blaauwgeers HG, Kessels AG, De Vente J, Liem AT, Steinbusch H, Hendrikse F. Source: American Journal of Ophthalmology. 2001 October; 132(4): 544-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589877&dopt=Abstract
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L-glutamine supplementation improves nelfinavir-associated diarrhea in HIVinfected individuals. Author(s): Huffman FG, Walgren ME. Source: Hiv Clinical Trials. 2003 September-October; 4(5): 324-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583848&dopt=Abstract
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Limited heat-shock protein 72 induction in Caco-2 cells by L-glutamine. Author(s): Lindemann G, Grohs M, Stange EF, Fellermann K. Source: Digestion. 2001; 64(2): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684820&dopt=Abstract
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Longitudinal pattern of glutamine/glutamate balance across the leg in long-stay intensive care unit patients. Author(s): Vesali RF, Klaude M, Rooyackers OE, TJader I, Barle H, Wernerman J. Source: Clinical Nutrition (Edinburgh, Lothian). 2002 December; 21(6): 505-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468371&dopt=Abstract
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Long-term culture of glutamine synthetase-transfected HepG2 cells in circulatory flow bioreactor for development of a bioartificial liver. Author(s): Enosawa S, Miyashita T, Suzuki S, Li XK, Tsunoda M, Amemiya H, Yamanaka M, Hiramatsu S, Tanimura N, Omasa T, Suga K, Matsumura T. Source: Cell Transplantation. 2000 September-October; 9(5): 711-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11144971&dopt=Abstract
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Loss of glutamine synthetase in the human epileptogenic hippocampus: possible mechanism for raised extracellular glutamate in mesial temporal lobe epilepsy. Author(s): Eid T, Thomas MJ, Spencer DD, Runden-Pran E, Lai JC, Malthankar GV, Kim JH, Danbolt NC, Ottersen OP, de Lanerolle NC. Source: Lancet. 2004 January 3; 363(9402): 28-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14723991&dopt=Abstract
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Low plasma glutamine after multiple trauma: relationship with intracellular glutamine in polymorphonuclear neutrophils during prolonged ICU stay. Author(s): Engel JM, Muhling J, Weiss S, Lohr T, Simonis Y, Menges T, Hempelmann G. Source: Acta Anaesthesiologica Scandinavica. 2003 July; 47(6): 707-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803588&dopt=Abstract
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Low serum concentrations of insulin-like growth factor-I in children with active Crohn disease: effect of enteral nutritional support and glutamine supplementation. Author(s): Akobeng AI, Clayton PE, Miller V, Hall CM, Thomas AG. Source: Scandinavian Journal of Gastroenterology. 2002 December; 37(12): 1422-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523592&dopt=Abstract
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Lymphocyte proliferation is possible with low concentrations of glycyl-glutamine. Author(s): Kohler H, Hartig-Knecht H, Ruggeberg J, Adam R, Schroten H. Source: European Journal of Nutrition. 2000 June; 39(3): 103-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918991&dopt=Abstract
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Metabolic response of muscle to alanine, glutamine, and valine supplementation during severe illness. Author(s): Gore DC, Wolfe RR. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 September-October; 27(5): 307-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971729&dopt=Abstract
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Mitochondrial glutathione depletion by glutamine in growing tumor cells. Author(s): Carretero J, Obrador E, Pellicer JA, Pascual A, Estrela JM. Source: Free Radical Biology & Medicine. 2000 November 1; 29(9): 913-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063916&dopt=Abstract
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Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut. Author(s): Coeffier M, Marion R, Ducrotte P, Dechelotte P. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(4): 407-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12880609&dopt=Abstract
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Molecular and functional analysis of glutamine uptake in human hepatoma and liverderived cells. Author(s): Bode BP, Fuchs BC, Hurley BP, Conroy JL, Suetterlin JE, Tanabe KK, Rhoads DB, Abcouwer SF, Souba WW. Source: American Journal of Physiology. Gastrointestinal and Liver Physiology. 2002 November; 283(5): G1062-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12381519&dopt=Abstract
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Molecular identification of human glutamine- and ammonia-dependent NAD synthetases. Carbon-nitrogen hydrolase domain confers glutamine dependency. Author(s): Hara N, Yamada K, Terashima M, Osago H, Shimoyama M, Tsuchiya M. Source: The Journal of Biological Chemistry. 2003 March 28; 278(13): 10914-21. Epub 2003 January 23. Erratum In: J Biol Chem. 2003 October 17; 278(42): 41572. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547821&dopt=Abstract
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Multiple replacements of glutamine 143 in human manganese superoxide dismutase: effects on structure, stability, and catalysis. Author(s): Leveque VJ, Stroupe ME, Lepock JR, Cabelli DE, Tainer JA, Nick HS, Silverman DN. Source: Biochemistry. 2000 June 20; 39(24): 7131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10852710&dopt=Abstract
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Muscle glutamine production in burn patients: the physiological meaning of tracer estimates. Author(s): Wagenmakers AJ. Source: Clinical Science (London, England : 1979). 2001 March; 100(3): 299-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11222116&dopt=Abstract
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NAC, glutamine, and alpha lipoic acid. Interview by John S. James. Author(s): Lands L. Source: Aids Treat News. 1997 April 4; (No 268): 2-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11364196&dopt=Abstract
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Neurodegeneration. A glutamine-rich trail leads to transcription factors. Author(s): Freiman RN, Tjian R. Source: Science. 2002 June 21; 296(5576): 2149-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12077389&dopt=Abstract
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Neuroprotection by glutamine synthetase. Author(s): Vardimon L. Source: Isr Med Assoc J. 2000 July; 2 Suppl: 46-51. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10909417&dopt=Abstract
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New data and concepts on glutamine and glucose metabolism in the gut. Author(s): Mithieux G. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2001 July; 4(4): 26771. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11458019&dopt=Abstract
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New developments in glutamine delivery. Author(s): Furst P. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2562S-8S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533314&dopt=Abstract
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Nitric oxide regulates the phosphorylation of the threonine-glutamine-tyrosine motif in proteins of human spermatozoa during capacitation. Author(s): Thundathil J, de Lamirande E, Gagnon C. Source: Biology of Reproduction. 2003 April; 68(4): 1291-8. Epub 2002 October 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606410&dopt=Abstract
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Nonlinear decrease over time in N-acetyl aspartate levels in the absence of neuronal loss and increases in glutamine and glucose in transgenic Huntington's disease mice. Author(s): Jenkins BG, Klivenyi P, Kustermann E, Andreassen OA, Ferrante RJ, Rosen BR, Beal MF. Source: Journal of Neurochemistry. 2000 May; 74(5): 2108-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10800956&dopt=Abstract
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N-terminal extension of canine glutamine synthetase created by splicing alters its enzymatic property. Author(s): Shin D, Park C. Source: The Journal of Biological Chemistry. 2004 January 9; 279(2): 1184-90. Epub 2003 October 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583610&dopt=Abstract
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Nuclear localization of a non-caspase truncation product of atrophin-1, with an expanded polyglutamine repeat, increases cellular toxicity. Author(s): Nucifora FC Jr, Ellerby LM, Wellington CL, Wood JD, Herring WJ, Sawa A, Hayden MR, Dawson VL, Dawson TM, Ross CA. Source: The Journal of Biological Chemistry. 2003 April 11; 278(15): 13047-55. Epub 2002 December 02. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464607&dopt=Abstract
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Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2000 August; 5(4): 290-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956377&dopt=Abstract
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Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, doubleblind, placebo-controlled study. Author(s): Clark RH, Feleke G, Din M, Yasmin T, Singh G, Khan FA, Rathmacher JA. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 May-June; 24(3): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850936&dopt=Abstract
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Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Author(s): Cockerham MB, Weinberger BB, Lerchie SB. Source: The Annals of Pharmacotherapy. 2000 March; 34(3): 300-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917373&dopt=Abstract
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Oral glutamine in paediatric oncology patients: a dose finding study. Author(s): Ward E, Picton S, Reid U, Thomas D, Gardener C, Smith M, Henderson M, Holden V, Kinsey S, Lewis I, Allgar V. Source: European Journal of Clinical Nutrition. 2003 January; 57(1): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548294&dopt=Abstract
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Oral glutamine in the prevention of fluorouracil induced intestinal toxicity: a double blind, placebo controlled, randomised trial. Author(s): Daniele B, Perrone F, Gallo C, Pignata S, De Martino S, De Vivo R, Barletta E, Tambaro R, Abbiati R, D'Agostino L. Source: Gut. 2001 January; 48(1): 28-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11115819&dopt=Abstract
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Oral glutamine supplements in autologous hematopoietic transplant: impact on gastrointestinal toxicity and plasma protein levels. Author(s): Canovas G, Leon-Sanz M, Gomez P, Valero MA, Gomis P, La Huerta JJ. Source: Haematologica. 2000 November; 85(11): 1229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064482&dopt=Abstract
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Oral glutamine: does it make sense? Author(s): Roth E. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 January; 17(1): 52-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165889&dopt=Abstract
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Overexpression of the complementary DNA for human glutamine:fructose-6phosphate amidotransferase in mesangial cells enhances glucose-induced fibronectin synthesis and transcription factor cyclic adenosine monophosphate-responsive element binding phosphorylation. Author(s): Singh LP, Alexander M, Greene K, Crook ED. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2003 February; 51(1): 32-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580319&dopt=Abstract
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Oxidation of glutamine by the splanchnic bed in humans. Author(s): Haisch M, Fukagawa NK, Matthews DE. Source: American Journal of Physiology. Endocrinology and Metabolism. 2000 April; 278(4): E593-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10751191&dopt=Abstract
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Palmitate-induced activation of the hexosamine pathway in human myotubes: increased expression of glutamine:fructose-6-phosphate aminotransferase. Author(s): Weigert C, Klopfer K, Kausch C, Brodbeck K, Stumvoll M, Haring HU, Schleicher ED. Source: Diabetes. 2003 March; 52(3): 650-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606504&dopt=Abstract
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Parenteral L-alanyl-L-glutamine improves 6-month outcome in critically ill patients. Author(s): Goeters C, Wenn A, Mertes N, Wempe C, Van Aken H, Stehle P, Bone HG. Source: Critical Care Medicine. 2002 September; 30(9): 2032-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352037&dopt=Abstract
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Phase III double-blind study of glutamine versus placebo for the prevention of acute diarrhea in patients receiving pelvic radiation therapy. Author(s): Kozelsky TF, Meyers GE, Sloan JA, Shanahan TG, Dick SJ, Moore RL, Engeler GP, Frank AR, McKone TK, Urias RE, Pilepich MV, Novotny PJ, Martenson JA; North Central Cancer Treatment Group. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2003 May 1; 21(9): 1669-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12721240&dopt=Abstract
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Phenotypic effects of expanded ataxin-1 polyglutamines with interruptions in vitro. Author(s): Calabresi V, Guida S, Servadio A, Jodice C. Source: Brain Research Bulletin. 2001 October-November 1; 56(3-4): 337-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719269&dopt=Abstract
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Phorbol esters rapidly attenuate glutamine uptake and growth in human colon carcinoma cells. Author(s): Pawlik TM, Souba WW, Sweeney TJ, Bode BP. Source: The Journal of Surgical Research. 2000 May 15; 90(2): 149-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10792956&dopt=Abstract
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Phosphorylation of human glutamine:fructose-6-phosphate amidotransferase by cAMP-dependent protein kinase at serine 205 blocks the enzyme activity. Author(s): Chang Q, Su K, Baker JR, Yang X, Paterson AJ, Kudlow JE. Source: The Journal of Biological Chemistry. 2000 July 21; 275(29): 21981-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10806197&dopt=Abstract
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Plasma glutamine and ammonia concentrations in ornithine carbamoyltransferase deficiency and citrullinaemia. Author(s): Wilson CJ, Lee PJ, Leonard JV. Source: Journal of Inherited Metabolic Disease. 2001 December; 24(7): 691-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11804205&dopt=Abstract
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Plasma glutamine and glutamate concentrations in Gabonese children with Plasmodium falciparum infection. Author(s): Planche T, Dzeing A, Emmerson AC, Onanga M, Kremsner PG, Engel K, Kombila M, Ngou-Milama E, Krishna S. Source: Qjm : Monthly Journal of the Association of Physicians. 2002 February; 95(2): 8997. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861956&dopt=Abstract
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Plasma glutamine depletion and patient outcome in acute ICU admissions. Author(s): Oudemans-van Straaten HM, Bosman RJ, Treskes M, van der Spoel HJ, Zandstra DF. Source: Intensive Care Medicine. 2001 January; 27(1): 84-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280678&dopt=Abstract
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Plasma taurine concentrations increase after enteral glutamine supplementation in trauma patients and stressed rats. Author(s): Boelens PG, Houdijk AP, de Thouars HN, Teerlink T, van Engeland MI, Haarman HJ, van Leeuwen PA. Source: The American Journal of Clinical Nutrition. 2003 January; 77(1): 250-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499349&dopt=Abstract
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Polyglutamine protein aggregates are dynamic. Author(s): Kim S, Nollen EA, Kitagawa K, Bindokas VP, Morimoto RI. Source: Nature Cell Biology. 2002 October; 4(10): 826-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12360295&dopt=Abstract
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Poly-L-glutamine forms cation channels: relevance to the pathogenesis of the polyglutamine diseases. Author(s): Monoi H, Futaki S, Kugimiya S, Minakata H, Yoshihara K. Source: Biophysical Journal. 2000 June; 78(6): 2892-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10827970&dopt=Abstract
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Postoperative glycyl-glutamine infusion reduces immunosuppression: partial prevention of the surgery induced decrease in HLA-DR expression on monocytes. Author(s): Spittler A, Sautner T, Gornikiewicz A, Manhart N, Oehler R, Bergmann M, Fugger R, Roth E. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 February; 20(1): 37-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11161542&dopt=Abstract
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Potential role of glutamine administration in inflammatory bowel disease. Author(s): Jonas CR, Ziegler TR. Source: Nestle Nutr Workshop Ser Clin Perform Programme. 1999; 2: 217-30; Discussion 230-5. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11490624&dopt=Abstract
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Presence of glutamine:fructose-6-phosphate amidotransferase for glucosamine-6phosphate synthesis in endothelial cells: effects of hyperglycaemia and glutamine. Author(s): Wu G, Haynes TE, Yan W, Meininger CJ. Source: Diabetologia. 2001 February; 44(2): 196-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270676&dopt=Abstract
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Prevention of chemotherapy and radiation toxicity with glutamine. Author(s): Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B. Source: Cancer Treatment Reviews. 2003 December; 29(6): 501-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585260&dopt=Abstract
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Primary structure, genomic organization, and functional and electrogenic characteristics of human system N 1, a Na+- and H+-coupled glutamine transporter. Author(s): Fei YJ, Sugawara M, Nakanishi T, Huang W, Wang H, Prasad PD, Leibach FH, Ganapathy V. Source: The Journal of Biological Chemistry. 2000 August 4; 275(31): 23707-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10823827&dopt=Abstract
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Prognostic significance of glutamine synthetase expression in unifocal advanced hepatocellular carcinoma. Author(s): Osada T, Nagashima I, Tsuno NH, Kitayama J, Nagawa H. Source: Journal of Hepatology. 2000 August; 33(2): 247-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10952242&dopt=Abstract
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Properties and regulation of glutamine transporter SN1 by protein kinases SGK and PKB. Author(s): Boehmer C, Okur F, Setiawan I, Broer S, Lang F. Source: Biochemical and Biophysical Research Communications. 2003 June 20; 306(1): 156-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12788082&dopt=Abstract
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Proteasomal interactors control activities as diverse as the cell cycle and glutaminergic neurotransmission. Author(s): Rezvani K, Mee M, Dawson S, McIlhinney J, Fujita J, Mayer RJ. Source: Biochemical Society Transactions. 2003 April; 31(2): 470-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653665&dopt=Abstract
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Protective effects of estrogens on polyglutamine-expanded androgen receptor aggregation in mice. Author(s): Darrington RS, Leigh PN, Gallo JM. Source: Neuroscience Letters. 2003 October 16; 350(1): 37-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12962912&dopt=Abstract
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Protein binding of a DRPLA family through arginine-glutamic acid dipeptide repeats is enhanced by extended polyglutamine. Author(s): Yanagisawa H, Bundo M, Miyashita T, Okamura-Oho Y, Tadokoro K, Tokunaga K, Yamada M. Source: Human Molecular Genetics. 2000 May 22; 9(9): 1433-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10814707&dopt=Abstract
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Protein kinase C activation of intestinal glutamine transport is mediated by mitogenactivated protein kinases. Author(s): Pan M, Wolfgang CA, Karinch AM, Lin C, Meng Q, Vary TC, Souba WW. Source: The Journal of Surgical Research. 2002 July; 106(1): 137-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127819&dopt=Abstract
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Proteomic identification of oxidatively modified proteins in Alzheimer's disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxy-terminal hydrolase L-1. Author(s): Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, Markesbery WR, Butterfield DA. Source: Free Radical Biology & Medicine. 2002 August 15; 33(4): 562-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160938&dopt=Abstract
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Proton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer's disease. Author(s): Hattori N, Abe K, Sakoda S, Sawada T. Source: Neuroreport. 2002 January 21; 13(1): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11924885&dopt=Abstract
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Purification and characterization of glutamine:fructose 6-phosphate amidotransferase from rat liver. Author(s): Huynh QK, Gulve EA, Dian T. Source: Archives of Biochemistry and Biophysics. 2000 July 15; 379(2): 307-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10898949&dopt=Abstract
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Purification of polyglutamine aggregates and identification of elongation factor1alpha and heat shock protein 84 as aggregate-interacting proteins. Author(s): Mitsui K, Nakayama H, Akagi T, Nekooki M, Ohtawa K, Takio K, Hashikawa T, Nukina N. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 November 1; 22(21): 9267-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417652&dopt=Abstract
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Quantification of glutamine in dried blood spots and plasma by tandem mass spectrometry for the biochemical diagnosis and monitoring of ornithine transcarbamylase deficiency. Author(s): Trinh MU, Blake J, Harrison JR, Gerace R, Ranieri E, Fletcher JM, Johnson DW. Source: Clinical Chemistry. 2003 April; 49(4): 681-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651832&dopt=Abstract
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Recruitment of nonexpanded polyglutamine proteins to intranuclear aggregates in neuronal intranuclear hyaline inclusion disease. Author(s): Takahashi J, Tanaka J, Arai K, Funata N, Hattori T, Fukuda T, Fujigasaki H, Uchihara T. Source: Journal of Neuropathology and Experimental Neurology. 2001 April; 60(4): 36976. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305872&dopt=Abstract
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Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Author(s): Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, Garrett T, Savage D, Antman K, Hesdorffer CS, Balmaceda C. Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 May; 7(5): 1192-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350883&dopt=Abstract
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Regulation of glutamine transport by the type I insulin-like growth factor receptor in a human neuroblastoma cell line. Author(s): Wang HS, Wasa M, Okada A. Source: Cancer Letters. 2001 July 10; 168(1): 81-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368881&dopt=Abstract
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Regulative capacity of glutamine. Author(s): Oehler R, Roth E. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2003 May; 6(3): 27782. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690259&dopt=Abstract
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Regulative potential of glutamine--relation to glutathione metabolism. Author(s): Roth E, Oehler R, Manhart N, Exner R, Wessner B, Strasser E, Spittler A. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 March; 18(3): 217-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882392&dopt=Abstract
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Relation between glutamine, branched-chain amino acids, and protein metabolism. Author(s): Holecek M. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 February; 18(2): 130-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844643&dopt=Abstract
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Relative effects of glucose and glutamine on reactive oxygen intermediate production by neutrophils. Author(s): Furukawa S, Saito H, Matsuda T, Inoue T, Fukatsu K, Han I, Ikeda S, Hidemura A, Muto T. Source: Shock (Augusta, Ga.). 2000; 13(4): 274-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10774615&dopt=Abstract
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Response of glutamine metabolism to glutamine-supplemented parenteral nutrition. Author(s): van Acker BA, Hulsewe KW, Wagenmakers AJ, von Meyenfeldt MF, Soeters PB. Source: The American Journal of Clinical Nutrition. 2000 September; 72(3): 790-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10966901&dopt=Abstract
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Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Author(s): May PE, Barber A, D'Olimpio JT, Hourihane A, Abumrad NN. Source: American Journal of Surgery. 2002 April; 183(4): 471-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975938&dopt=Abstract
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117
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Role of glucose in the regulation of glutamine metabolism in health and in type 1 insulin-dependent diabetes. Author(s): Hankard RG, Haymond MW, Darmaun D. Source: American Journal of Physiology. Endocrinology and Metabolism. 2000 September; 279(3): E608-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10950829&dopt=Abstract
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Role of glutamine depletion in severe illness. Author(s): Darmaun D. Source: Diabetes Nutr Metab. 2000 February; 13(1): 25-30. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10824720&dopt=Abstract
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Role of glutamine in cerebral nitrogen metabolism and ammonia neurotoxicity. Author(s): Cooper AJ. Source: Mental Retardation and Developmental Disabilities Research Reviews. 2001; 7(4): 280-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11754523&dopt=Abstract
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Role of glutamine on the de novo purine nucleotide synthesis in Caco-2 cells. Author(s): Boza JJ, Moennoz D, Bournot CE, Blum S, Zbinden I, Finot PA, Ballevre O. Source: European Journal of Nutrition. 2000 February; 39(1): 38-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10900556&dopt=Abstract
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Role of L-glutamine in critical illness: new insights. Author(s): Kelly D, Wischmeyer PE. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2003 March; 6(2): 21722. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589192&dopt=Abstract
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SCA1 molecular genetics: a history of a 13 year collaboration against glutamines. Author(s): Orr HT, Zoghbi HY. Source: Human Molecular Genetics. 2001 October 1; 10(20): 2307-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11673415&dopt=Abstract
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SCA17, a novel autosomal dominant cerebellar ataxia caused by an expanded polyglutamine in TATA-binding protein. Author(s): Nakamura K, Jeong SY, Uchihara T, Anno M, Nagashima K, Nagashima T, Ikeda S, Tsuji S, Kanazawa I. Source: Human Molecular Genetics. 2001 July 1; 10(14): 1441-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448935&dopt=Abstract
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Serum and CSF glutamine levels in valproate-related hyperammonemic encephalopathy. Author(s): Vossler DG, Wilensky AJ, Cawthon DF, Kraemer DL, Ojemann LM, Caylor LM, Morgan JD. Source: Epilepsia. 2002 February; 43(2): 154-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11903461&dopt=Abstract
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Small glutamine-rich protein/viral protein U-binding protein is a novel cochaperone that affects heat shock protein 70 activity. Author(s): Angeletti PC, Walker D, Panganiban AT. Source: Cell Stress & Chaperones. 2002 July; 7(3): 258-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482202&dopt=Abstract
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Small glutamine-rich tetratricopeptide repeat-containing protein (SGT) interacts with the ubiquitin-dependent endocytosis (UbE) motif of the growth hormone receptor. Author(s): Schantl JA, Roza M, De Jong AP, Strous GJ. Source: The Biochemical Journal. 2003 August 1; 373(Pt 3): 855-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735788&dopt=Abstract
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Solution studies of chymotrypsin inhibitor-2 glutamine insertion mutants show no interglutamine interactions. Author(s): Gordon-Smith DJ, Carbajo RJ, Stott K, Neuhaus D. Source: Biochemical and Biophysical Research Communications. 2001 January 26; 280(3): 855-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11162601&dopt=Abstract
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Somatic instability of the DNA sequences encoding the polymorphic polyglutamine tract of the AIB1 gene. Author(s): Dai P, Wong LJ. Source: Journal of Medical Genetics. 2003 December; 40(12): 885-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684685&dopt=Abstract
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Special feature for the Olympics: effects of exercise on the immune system: modification of immune responses to exercise by carbohydrate, glutamine and antioxidant supplements. Author(s): Gleeson M, Bishop NC. Source: Immunology and Cell Biology. 2000 October; 78(5): 554-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050539&dopt=Abstract
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119
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Specific glutamine and asparagine residues of gamma-S crystallin are resistant to in vivo deamidation. Author(s): Takemoto L, Boyle D. Source: The Journal of Biological Chemistry. 2000 August 25; 275(34): 26109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10843993&dopt=Abstract
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Specificity determining residues in ammonia- and glutamine-dependent carbamoyl phosphate synthetases. Author(s): Saeed-Kothe A, Powers-Lee SG. Source: The Journal of Biological Chemistry. 2002 March 1; 277(9): 7231-8. Epub 2001 December 27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756425&dopt=Abstract
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Spinocerebellar ataxia type 6: channelopathy or glutamine repeat disorder? Author(s): Frontali M. Source: Brain Research Bulletin. 2001 October-November 1; 56(3-4): 227-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11719255&dopt=Abstract
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Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Author(s): Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E, Prochazka B, Kozak T. Source: Bone Marrow Transplantation. 2002 December; 30(12): 953-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476290&dopt=Abstract
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Starvation-induced lysosomal degradation of aldolase B requires glutamine 111 in a signal sequence for chaperone-mediated transport. Author(s): Susan PP, Dunn WA Jr. Source: Journal of Cellular Physiology. 2001 April; 187(1): 48-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241348&dopt=Abstract
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Steroid receptor coactivator-3 glutamine repeat polymorphism and the androgen insensitivity syndrome. Author(s): Mongan NP, Jaaskelainen J, Bhattacharyya S, Leu RM, Hughes IA. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2003 February; 148(2): 277-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590649&dopt=Abstract
120
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Strong aggregation and increased toxicity of polyleucine over polyglutamine stretches in mammalian cells. Author(s): Dorsman JC, Pepers B, Langenberg D, Kerkdijk H, Ijszenga M, den Dunnen JT, Roos RA, van Ommen GJ. Source: Human Molecular Genetics. 2002 June 15; 11(13): 1487-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12045202&dopt=Abstract
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Structural features associated with the binding of glutamine-containing peptides to Factor XIII. Author(s): Marinescu A, Cleary DB, Littlefield TR, Maurer MC. Source: Archives of Biochemistry and Biophysics. 2002 October 1; 406(1): 9-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234485&dopt=Abstract
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Sub-lethal concentrations of activated complement increase rat lymphocyte glutamine utilization and oxidation while lethal concentrations cause death by a mechanism involving ATP depletion. Author(s): Bacurau RF, O'Toole CE, Newsholme P, Costa Rosa LF. Source: Cell Biochemistry and Function. 2002 September; 20(3): 183-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12125093&dopt=Abstract
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SUMO-1 co-localized with mutant atrophin-1 with expanded polyglutamines accelerates intranuclear aggregation and cell death. Author(s): Terashima T, Kawai H, Fujitani M, Maeda K, Yasuda H. Source: Neuroreport. 2002 December 3; 13(17): 2359-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12488827&dopt=Abstract
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Supplemental glutamine augments phagocytosis and reactive oxygen intermediate production by neutrophils and monocytes from postoperative patients in vitro. Author(s): Furukawa S, Saito H, Inoue T, Matsuda T, Fukatsu K, Han I, Ikeda S, Hidemura A. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2000 May; 16(5): 323-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793298&dopt=Abstract
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The anabolic effects of recombinant human growth hormone and glutamine on parenterally fed, short bowel rats. Author(s): Gu Y, Wu ZH. Source: World Journal of Gastroenterology : Wjg. 2002 August; 8(4): 752-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174391&dopt=Abstract
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The BCAA-BCKA cycle: its relation to alanine and glutamine synthesis and protein balance. Author(s): Holecek M. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 January; 17(1): 70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165898&dopt=Abstract
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The conserved glutamine-rich region of chick csal1 and csal3 mediates protein interactions with other spalt family members. Implications for Townes-Brocks syndrome. Author(s): Sweetman D, Smith T, Farrell ER, Chantry A, Munsterberg A. Source: The Journal of Biological Chemistry. 2003 February 21; 278(8): 6560-6. Epub 2002 December 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482848&dopt=Abstract
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The effect of glutamine on protein balance and amino acid flux across arm and leg tissues in healthy volunteers. Author(s): Svanberg E, Moller-Loswick AC, Matthews DE, Korner U, Lundholm K. Source: Clinical Physiology (Oxford, England). 2001 July; 21(4): 478-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442580&dopt=Abstract
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The effect of glutamine supplementation in patients following elective surgery and accidental injury. Author(s): Wilmore DW. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2543S-9S; Discussion 2550S-1S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533310&dopt=Abstract
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The effect of glutamine-supplemented total parenteral nutrition on nitrogen economy depends on severity of diseases in surgical patients. Author(s): Lin MT, Kung SP, Yeh SL, Lin C, Lin TH, Chen KH, Liaw KY, Lee PH, Chang KJ, Chen WJ. Source: Clinical Nutrition (Edinburgh, Lothian). 2002 June; 21(3): 213-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12127929&dopt=Abstract
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The effect of polyglutamine expansion in the human androgen receptor on its ability to suppress beta-catenin-Tcf/Lef dependent transcription. Author(s): Cullen DA, Killick R, Leigh PN, Gallo JM. Source: Neuroscience Letters. 2004 January 2; 354(1): 54-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14698481&dopt=Abstract
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The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial. Author(s): Zhou YP, Jiang ZM, Sun YH, Wang XR, Ma EL, Wilmore D. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 July-August; 27(4): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903886&dopt=Abstract
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The effectiveness of growth hormone, glutamine and a low-fat diet containing highcarbohydrate on the enhancement of the function of remnant intestine among patients with short bowel syndrome: a review of published trials. Author(s): Li-Ling, Irving M. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 June; 20(3): 199-204. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11407865&dopt=Abstract
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The effects of 8 weeks of creatine monohydrate and glutamine supplementation on body composition and performance measures. Author(s): Lehmkuhl M, Malone M, Justice B, Trone G, Pistilli E, Vinci D, Haff EE, Kilgore JL, Haff GG. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2003 August; 17(3): 425-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930166&dopt=Abstract
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The effects of high-dose glutamine ingestion on weightlifting performance. Author(s): Antonio J, Sanders MS, Kalman D, Woodgate D, Street C. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2002 February; 16(1): 157-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834123&dopt=Abstract
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The evidence for glutamine use in the critically-ill. Author(s): Griffiths RD. Source: The Proceedings of the Nutrition Society. 2001 August; 60(3): 403-10. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681816&dopt=Abstract
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The glutamine 27 glutamic acid polymorphism of the beta2-adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population-based study in Spain. Author(s): Gonzalez Sanchez JL, Proenza AM, Martinez Larrad MT, Ramis JM, Fernandez Perez C, Palou A, Serrano Rios M. Source: Clinical Endocrinology. 2003 October; 59(4): 476-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14510910&dopt=Abstract
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The heterodimeric amino acid transporter 4F2hc/y+LAT2 mediates arginine efflux in exchange with glutamine. Author(s): Broer A, Wagner CA, Lang F, Broer S. Source: The Biochemical Journal. 2000 August 1; 349 Pt 3: 787-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10903140&dopt=Abstract
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The influence of diet and exercise on muscle and plasma glutamine concentrations. Author(s): Blanchard MA, Jordan G, Desbrow B, MacKinnon LT, Jenkins DG. Source: Medicine and Science in Sports and Exercise. 2001 January; 33(1): 69-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194114&dopt=Abstract
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The influence of the buried glutamine or glutamate residue in position 6 on the structure of immunoglobulin variable domains. Author(s): Honegger A, Pluckthun A. Source: Journal of Molecular Biology. 2001 June 8; 309(3): 687-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11397089&dopt=Abstract
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The ins and outs of a polyglutamine neurodegenerative disease: spinocerebellar ataxia type 1 (SCA1). Author(s): Orr HT. Source: Neurobiology of Disease. 2000 June; 7(3): 129-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10860780&dopt=Abstract
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The local vascular tolerance to an intravenous infusion of a concentrated glutamine solution in ICU patients. Author(s): Berg A, Forsberg E, Wernerman J. Source: Clinical Nutrition (Edinburgh, Lothian). 2002 April; 21(2): 135-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12056785&dopt=Abstract
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The metastatic suppressor Nm23-H1 interacts with EBNA3C at sequences located between the glutamine- and proline-rich domains and can cooperate in activation of transcription. Author(s): Subramanian C, Robertson ES. Source: Journal of Virology. 2002 September; 76(17): 8702-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163590&dopt=Abstract
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The polyglutamine expansion in spinocerebellar ataxia type 6 causes a beta subunitspecific enhanced activation of P/Q-type calcium channels in Xenopus oocytes. Author(s): Restituito S, Thompson RM, Eliet J, Raike RS, Riedl M, Charnet P, Gomez CM. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2000 September 1; 20(17): 6394-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10964945&dopt=Abstract
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The polyglutamine motif is highly conserved at the Clock locus in various organisms and is not polymorphic in humans. Author(s): Saleem Q, Anand A, Jain S, Brahmachari SK. Source: Human Genetics. 2001 August; 109(2): 136-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11511917&dopt=Abstract
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The potential mechanism for glutamine-induced collagen biosynthesis in cultured human skin fibroblasts. Author(s): Karna E, Miltyk W, Wolczynski S, Palka JA. Source: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. 2001 August; 130(1): 23-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11470441&dopt=Abstract
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The relation between glutamine and the immunodepression observed in exercise. Author(s): Castell LM, Newsholme EA. Source: Amino Acids. 2001; 20(1): 49-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310930&dopt=Abstract
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The relationship of plasma glutamine to ammonium and of glycine to acid-base balance in propionic acidaemia. Author(s): Al-Hassnan ZN, Boyadjiev SA, Praphanphoj V, Hamosh A, Braverman NE, Thomas GH, Geraghty MT. Source: Journal of Inherited Metabolic Disease. 2003; 26(1): 89-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12872849&dopt=Abstract
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The role of L-alanyl-L-glutamine in the immune response in vitro. Author(s): Kircher B, Eibl G, Enrich B, Latzer K, Herold M, Niederwieser D. Source: Wiener Klinische Wochenschrift. 2002 August 30; 114(15-16): 702-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12602115&dopt=Abstract
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The XRCC1 399 glutamine allele is a risk factor for adenocarcinoma of the lung. Author(s): Divine KK, Gilliland FD, Crowell RE, Stidley CA, Bocklage TJ, Cook DL, Belinsky SA. Source: Mutation Research. 2001 January 5; 461(4): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104903&dopt=Abstract
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Total parenteral nutrition enriched with arginine and glutamate generates glutamine and limits protein catabolism in surgical patients hospitalized in intensive care units. Author(s): Berard MP, Zazzo JF, Condat P, Vasson MP, Cynober L. Source: Critical Care Medicine. 2000 November; 28(11): 3637-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098966&dopt=Abstract
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Transfer of glutamine between astrocytes and neurons. Author(s): Broer S, Brookes N. Source: Journal of Neurochemistry. 2001 May; 77(3): 705-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331400&dopt=Abstract
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Transglutamines and endocrine system (minireview). Author(s): Dvorcakova M, Macejova D, Pallet V, Higueret P, Vasson MP, Rock E, Brtko J. Source: Endocrine Regulations. 2002 March; 36(1): 31-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11971749&dopt=Abstract
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Ultrastructure of nuclear aggregates formed by expressing an expanded polyglutamine. Author(s): Hazeki N, Tsukamoto T, Yazawa I, Koyama M, Hattori S, Someki I, Iwatsubo T, Nakamura K, Goto J, Kanazawa I. Source: Biochemical and Biophysical Research Communications. 2002 June 7; 294(2): 429-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12051730&dopt=Abstract
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Unregulated elevation of glutamate dehydrogenase activity induces glutaminestimulated insulin secretion: identification and characterization of a GLUD1 gene mutation and insulin secretion studies with MIN6 cells overexpressing the mutant glutamate dehydrogenase. Author(s): Tanizawa Y, Nakai K, Sasaki T, Anno T, Ohta Y, Inoue H, Matsuo K, Koga M, Furukawa S, Oka Y. Source: Diabetes. 2002 March; 51(3): 712-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11872671&dopt=Abstract
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Uptake of 14C- and 11C-labeled glutamate, glutamine and aspartate in vitro and in vivo. Author(s): Wu F, Orlefors H, Bergstrom M, Antoni G, Omura H, Eriksson B, Watanabe Y, Langstrom B. Source: Anticancer Res. 2000 January-February; 20(1A): 251-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10769663&dopt=Abstract
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Where is the glutamine? Intradialytic supplementation may not solve all issues in amino acid balance. Author(s): Solomons NW, Stehle P, Furst P. Source: The American Journal of Clinical Nutrition. 2000 November; 72(5): 1236-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063458&dopt=Abstract
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Whole body and skeletal muscle glutamine metabolism in healthy subjects. Author(s): Mittendorfer B, Volpi E, Wolfe RR. Source: American Journal of Physiology. Endocrinology and Metabolism. 2001 February; 280(2): E323-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158937&dopt=Abstract
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CHAPTER 2. NUTRITION AND GLUTAMINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and glutamine.
Finding Nutrition Studies on Glutamine The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “glutamine” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following is a typical result when searching for recently indexed consumer information on glutamine: •
Glutamine in total parenteral nutrition. Author(s): Texas A&M University, Round Rock, TX. Source: Shipley, S.G. Nutrition-today (USA). (April 1996). volume 31(2) page 74-77.
Additional consumer oriented references include: •
Is glutamine a conditionally essential amino acid. Source: Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. August 1990. volume 48 (8) page 297-309. 0029-6643
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Muscle provides glutamine to the immune system. Source: Nutr-Rev. New York, N.Y. : Springer-Verlag New York Inc. October 1990. volume 48 (10) page 390-392. 0029-6643
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The Journal of Biological Chemistry, Volume 249, 1974: Uptake and metabolism of plasma glutamine by the small intestine. Source: Windmueller, H G Spaeth, A E Nutr-Revolume 1990 August; 48(8): 310-2 00296643
The following information is typical of that found when using the “Full IBIDS Database” to search for “glutamine” (or a synonym): •
Both glucose-insulin-potassium and glutamine in warm blood cardioplegia increase the rates of myocardial glucose and free fatty acid oxidation. Author(s): Department of Cardiothoracic and Vascular Surgery, School of Medicine, University of Tromso, Norway.
[email protected] Source: Elvenes, O P Korvald, C Irtun, O Larsen, T Sorlie, D Scand-Cardiovasc-J. 2002 February; 36(1): 19-26 1401-7431
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Changes in the nutritional state and immune-serological parameters of esophagectomized patients fed jejunaly with glutamine-poor and glutamine-rich nutriments. Author(s): Second Department of Surgery, Medical and Health Science Centre School of Medicine, University of Debrecen, Moricz Zs. Krt. 22., Debrecen H-4004, Hungary.
[email protected] Source: Hallay, J Kovacs, G Kiss Sz, S Farkas, M Lakos, G Sipka, S Bodolay, E Sapy, P Hepatogastroenterology. 2002 Nov-December; 49(48): 1555-9 0172-6390
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Clinical application of glutamine therapy. Source: Abood, S.K. Proc-North-Am-Vet-Conf. [Gainesville, Fla.] : Eastern States Veterinary Association, 1992-. 1998. volume 12 page 429.
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Conditionally indispensable amino acids (glutamine, cyst(e)ine, tyrosine, arginine, ornithine, taurine) in enteral feeding and the dipeptide concept. Author(s): Institute for Biological Chemistry and Nutrition, Stuttgart, Germany. Source: Furst, P Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 2000; 3: 199-217; discussion 217-9 1422-7584
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Effect of glutamine supplementation combined with resistance training in young adults. Author(s): College of Kinesiology, University of Saskatchewan, Saskatoon, Canada.
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Source: Candow, D G Chilibeck, P D Burke, D G Davison, K S Smith Palmer, T Eur-JAppl-Physiol. 2001 December; 86(2): 142-9 1439-6319 •
Effects of oral supplement of L-glutamine on diverted colon wall. Author(s): Colorectal Surgery Division, Department of Surgery, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
[email protected] Source: Paulo, F L J-Cell-Mol-Med. 2002 Jul-September; 6(3): 377-82 1582-1838
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Evidence that glutamine is involved in neutrophil function. Author(s): Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, SP, Brazil.
[email protected] Source: Pithon Curi, Tania C Trezena, Ariane G Tavares Lima, Wothan Curi, Rui CellBiochem-Funct. 2002 June; 20(2): 81-6 0263-6484
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Glutamine and wound healing. Author(s): Pembroke Pines, FL, USA.
[email protected] Source: Collins, N Adv-Skin-Wound-Care. 2002 Sep-October; 15(5): 233-4 1527-7941
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Glutamine decreases interleukin-8 and interleukin-6 but not nitric oxide and prostaglandins e(2) production by human gut in-vitro. Author(s): Appareil Digestif Environnement et Nutrition (ADEN EA 3234), Rouen, France. Source: Coeffier, M Marion, R Leplingard, A Lerebours, E Ducrotte, P Dechelotte, P Cytokine. 2002 April 21; 18(2): 92-7 1043-4666
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Glutamine for short-bowel syndrome. Source: Buchman, A L Curr-Gastroenterol-Repage 2002 August; 4(4): 321 1522-8037
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Glutamine metabolism in the fetus and critically ill low birth weight neonate. Author(s): University of Florida, Shands Children's Hospital at the University of Florida, Gainesville, USA. Source: Neu, J Auestad, N DeMarco, V G Adv-Pediatr. 2002; 49: 203-26 0065-3101
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Glutamine protects activated human T cells from apoptosis by up-regulating glutathione and Bcl-2 levels. Author(s): Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, Kaohsiung, Taiwan. Source: Chang, W K Yang, K D Chuang, H January, J T Shaio, M F Clin-Immunol. 2002 August; 104(2): 151-60 1521-6616
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Glutamine supplementation for prevention of morbidity in preterm infants (Cochrane Review). Author(s): Neonatal Intensive Care Unit, Royal Maternity Hospital, Grosvenor Road, Belfast, Northern Ireland, UK.
[email protected] Source: Tubman, T R Thompson, S W Cochrane-Database-Syst-Revolume 2001; 4: CD001457 1469-493X
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Glutamine-enhanced nutrition in the critically ill patient. Author(s): Intensive Care Medicine Research Group, Department of Medicine, University of Liverpool, Liverpool L69 3GA. Source: Andrews, Francis Griffiths, Richard Hosp-Med. 2002 March; 63(3): 144-7 14623935
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Identification of L-glutamine: 2-deoxy-scyllo-inosose aminotransferase required for the biosynthesis of butirosin in Bacillus circulans. Author(s): Department of Chemistry, Tokyo Institute of Technology, Japan. Source: Tamegai, H Nango, E Kuwahara, M Yamamoto, H Ota, Y Kuriki, H Eguchi, T Kakinuma, K J-Antibiot-(Tokyo). 2002 August; 55(8): 707-14 0021-8820
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Influence of glutamine and glycyl-glutamine on in vitro lymphocyte proliferation in children with solid tumors. Author(s): Department of Pediatrics, Heinrich-Heine-Universitat, Dusseldorf, Germany. Source: Kohler, H Klowik, M Brand, O Gobel, U Schroten, H Support-Care-Cancer. 2001 June; 9(4): 261-6 0941-4355
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Inhibition of glutamine synthetase in a549 cells during hyperoxia. Author(s): Department of Pediatrics, Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
[email protected] Source: McGrath Morrow, S A Stahl, J Am-J-Respir-Cell-Mol-Biol. 2002 July; 27(1): 99106 1044-1549
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Lethality of standard total parenteral nutrition following major liver resection in rats is prevented by high arginine and high branched chain amino acids but not by glutamine. Author(s): Department of Surgery, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA. Source: Qiu, J G Delany, H M Teh, E L Gliedman, M L Chang, C J Levenson, S M JAssoc-Acad-Minor-Phys. 2001 March; 12(1-2): 109-18 1048-9886
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L-glutamine. Source: Anonymous Altern-Med-Revolume 2001 August; 6(4): 406-10 1089-5159
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Plasma glutamine and glutamate concentrations in Gabonese children with Plasmodium falciparum infection. Author(s): Department of Infectious Diseases, St George's Hospital Medical School, Cranmer Terrace, London, UK. Source: Planche, T Dzeing, A Emmerson, A C Onanga, M Kremsner, P G Engel, K Kombila, M Ngou Milama, E Krishna, S QJM. 2002 February; 95(2): 89-97 1460-2725
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Possible role of glutamate, aspartate, glutamine, GABA or taurine on cadmium toxicity on the hypothalamic pituitary axis activity in adult male rats. Author(s): Laboratorio de Toxicologia, Facultad de Ciencias, Universidad de Vigo, Las Lagunas, Orense, Spain.
[email protected] Source: Lafuente, A Esquifino, A I Biometals. 2002 June; 15(2): 183-7 0966-0844
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Potential role of glutamine administration in inflammatory bowel disease. Author(s): Department of Medicine, Division of Endocrinology and Metabolism, Nutrition and Health Sciences Program, Emory University School of Medicine, Atlanta, Ga., USA. Source: Jonas, C R Ziegler, T R Nestle-Nutr-Workshop-Ser-Clin-Perform-Programme. 1999; 2: 217-30; discussion 230-5 1422-7584
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Preference for a solution of branched-chain amino acids plus glutamine and arginine correlates with free running activity in rats: involvement of serotonergic-dependent processes of lateral hypothalamus. Author(s): Ajinomoto Co. Inc., Central Research Laboratories, Kawasaki, Japan.
[email protected] Source: Smriga, M Kameishi, M Tanaka, T Kondoh, T Torii, K Nutr-Neurosci. 2002 June; 5(3): 189-99 1028-415X
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Preventive effect of glutamine on intestinal barrier dysfunction induced by severe trauma. Author(s): Burn Institute, Chinese PLA 304 Hospital, 51 Fu Cheng Road, Beijing 100037,China.
[email protected]
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Source: Li, June You Lu, Yi Hu, Sen Sun, Dan Yao, Yong Ming World-J-Gastroenterol. 2002 February; 8(1): 168-71 1007-9327 •
Prolonged dietary treatment with conjugated linoleic acid stimulates porcine muscle peroxisome proliferator activated receptor gamma and glutamine-fructose aminotransferase gene expression in vivo. Author(s): Meat Research Section, Agriculture and Agri-Food Canada, Lacombe Research Centre, 6000 C&E Trail, Alberta, Canada T4L 1W1.
[email protected] Source: Meadus, W J MacInnis, R Dugan, M E R J-Mol-Endocrinol. 2002 April; 28(2): 7986 0952-5041
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Proton MR spectroscopic study at 3 Tesla on glutamate/glutamine in Alzheimer's disease. Author(s): BF Research Institute, Inc, National Cardiovascular Center, Suita, Osaka, Japan. Source: Hattori, Noriaki Abe, Kazuo Sakoda, Saburo Sawada, Tohru Neuroreport. 2002 January 21; 13(1): 183-6 0959-4965
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Synthesis, screening and quantitative structure-activity relationship (QSAR) studies of some glutamine analogues for possible anticancer activity. Author(s): Division of Medicinal Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India.
[email protected] Source: Srikanth, K KuMarch, ChA Ghosh, B Jha, T Bioorg-Med-Chem. 2002 July; 10(7): 2119-31 0968-0896
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The amino acids precursory to proteins are primary human food: proline, glutamine, and arginine found free in the juices of common vegetables and herbs. Source: Kapuler, A.M. Gurusiddiah, S. J-med-food. Larchmont, NY : Mary Ann Liebert, Inc., c1998-. 1998. volume 1 (2) page 97-115. 1096-620X
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The anabolic effects of recombinant human growth hormone and glutamine on parenterally fed, short bowel rats. Author(s): Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Second Medical University, Shanghai 200011, China.
[email protected] Source: Gu, Y Wu, Z H World-J-Gastroenterol. 2002 August; 8(4): 752-7 1007-9327
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The effects of high-dose glutamine ingestion on weightlifting performance. Author(s): Sports Science Laboratory, University of Delaware, Newark, Delaware 19716, USA. Source: Antonio, Jose Sanders, Michael S Kalman, Douglas Woodgate, Derek Street, Chris J-Strength-Cond-Res. 2002 February; 16(1): 157-60 1064-8011
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The influence of L-glutamine on the depression of hepatic cytochrome P450 activity in male rats caused by total parenteral nutrition. Author(s): Department of Industrial and Physical Pharmacy, School of Pharmacy, Purdue University, West Lafayette, Indiana, USA. Source: Shaw, Andrew A Hall, Stephen D Franklin, Michael R Galinsky, Raymond E Drug-Metab-Dispos. 2002 February; 30(2): 177-82 0090-9556
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Thermostability of manganese- and iron-superoxide dismutases from Escherichia coli is determined by the characteristic position of a glutamine residue. Author(s): Department of Physiology and Biochemistry, University of Malta, Msida, Malta. Source: Hunter, T Bannister, J V Hunter, G J Eur-J-Biochem. 2002 November; 269(21): 5137-48 0014-2956
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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to glutamine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Minerals Cisplatin Source: Healthnotes, Inc.; www.healthnotes.com
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Food and Diet HMB Source: Healthnotes, Inc.; www.healthnotes.com Wound Healing Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND GLUTAMINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to glutamine. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to glutamine and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “glutamine” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to glutamine: •
5-fluorouracil and folinic acid-induced mucositis: no effect of oral glutamine supplementation. Author(s): Jebb SA, Osborne RJ, Maughan TS, Mohideen N, Mack P, Mort D, Shelley MD, Elia M. Source: British Journal of Cancer. 1994 October; 70(4): 732-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7917930&dopt=Abstract
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A cDNA sequence encoding glutamine synthetase is preferentially expressed in nodules of Vigna aconitifolia. Author(s): Lin Z, Miao GH, Verma DP. Source: Plant Physiology. 1995 January; 107(1): 279-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7870822&dopt=Abstract
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A clinical study of the effectiveness of oral glutamine supplementation during total parenteral nutrition: influence on mesenteric mononuclear cells. Author(s): Aosasa S, Mochizuki H, Yamamoto T, Ono S, Ichikura T. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1999 September-October; 23(5 Suppl): S41-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483893&dopt=Abstract
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A double blind, randomised, controlled trial of glutamine supplementation in parenteral nutrition. Author(s): Powell-Tuck J, Jamieson CP, Bettany GE, Obeid O, Fawcett HV, Archer C, Murphy DL. Source: Gut. 1999 July; 45(1): 82-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10369709&dopt=Abstract
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A strong constitutive positive element is essential for the ammonium-regulated expression of a soybean gene encoding cytosolic glutamine synthetase. Author(s): Terce-Laforgue T, Carrayol E, Cren M, Desbrosses G, Hecht V, Hirel B. Source: Plant Molecular Biology. 1999 February; 39(3): 551-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10092182&dopt=Abstract
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Acute effects of intravenous glutamine supplementation on protein metabolism in very low birth weight infants: a stable isotope study. Author(s): des Robert C, Le Bacquer O, Piloquet H, Roze JC, Darmaun D. Source: Pediatric Research. 2002 January; 51(1): 87-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756645&dopt=Abstract
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Altered kinetic properties of tyrosine-183 to cysteine mutation in glutamine synthetase of anabaena variabilis strain SA1 is responsible for excretion of ammonium ion produced by nitrogenase. Author(s): Healy FG, Latorre C, Albrecht SL, Reddy PM, Shanmugam KT. Source: Current Microbiology. 2003 June; 46(6): 423-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12732949&dopt=Abstract
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An alternative method to supplement glutamine in parenteral nutrition? Author(s): Sandifer DP. Source: Critical Care Medicine. 2000 November; 28(11): 3761-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11098992&dopt=Abstract
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Antipeptide antibodies that can distinguish specific subunit polypeptides of glutamine synthetase from bean (Phaseolus vulgaris L.). Author(s): Cai X, Henry RL, Takemoto LJ, Guikema JA, Wong PP.
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Source: Plant Physiology. 1992; 98: 402-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11537881&dopt=Abstract •
Assessment of the safety of glutamine and other amino acids. Author(s): Garlick PJ. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2556S-61S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533313&dopt=Abstract
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Bcl-xL expression interferes with the effects of L-glutamine supplementation on hybridoma cultures. Author(s): Charbonneau JR, Furtak T, Lefebvre J, Gauthier ER. Source: Biotechnology and Bioengineering. 2003 February 5; 81(3): 279-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12474250&dopt=Abstract
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Bidirectional supply of glutamine maintains enterocyte ATP content in the in vitro using chamber model. Author(s): Yang H, Soderholm JD, Larsson J, Permert J, Lindgren J, Wiren M. Source: International Journal of Colorectal Disease. 2000 November; 15(5-6): 291-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11151432&dopt=Abstract
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Cloning and characterisation of glutamine synthetase from Colletotrichum gloeosporioides and demonstration of elevated expression during pathogenesis on Stylosanthes guianensis. Author(s): Stephenson SA, Green JR, Manners JM, Maclean DJ. Source: Current Genetics. 1997 May; 31(5): 447-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9162117&dopt=Abstract
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Comparison of a immunonutrition formula enriched arginine, glutamine and omega3 fatty acid, with a currently high-enriched enteral nutrition for trauma patients. Author(s): Chuntrasakul C, Siltham S, Sarasombath S, Sittapairochana C, Leowattana W, Chockvivatanavanit S, Bunnak A. Source: J Med Assoc Thai. 2003 June; 86(6): 552-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12924804&dopt=Abstract
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Complementary expression of glutamine synthetase and carbamoylphosphate synthetase I in ornithine carbamoyltransferase-deficient mouse liver (spf-ash mouse). Author(s): Shiojiri N, Ohta T, Ogawa K, Gebhardt R. Source: Histochemistry and Cell Biology. 1997 December; 108(6): 489-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9450631&dopt=Abstract
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Control of de novo purine biosynthesis genes in ureide-producing legumes: induction of glutamine phosphoribosylpyrophosphate amidotransferase gene and
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characterization of its cDNA from soybean and Vigna. Author(s): Kim JH, Delauney AJ, Verma DP. Source: The Plant Journal : for Cell and Molecular Biology. 1995 January; 7(1): 77-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7894513&dopt=Abstract •
Decreased mortality and infectious morbidity in adult burn patients given enteral glutamine supplements: a prospective, controlled, randomized clinical trial. Author(s): Garrel D, Patenaude J, Nedelec B, Samson L, Dorais J, Champoux J, D'Elia M, Bernier J. Source: Critical Care Medicine. 2003 October; 31(10): 2444-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14530749&dopt=Abstract
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Decreased mortality and infectious morbidity in adult burn patients with enteral glutamine supplements. Author(s): Garrel DR, Bernier J. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(S1): S78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684041&dopt=Abstract
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Dietary glutamine supplementation prevents jejunal atrophy in weaned pigs. Author(s): Wu G, Meier SA, Knabe DA. Source: The Journal of Nutrition. 1996 October; 126(10): 2578-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8857520&dopt=Abstract
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Dietary glutamine supplementation reduces plasma nitrate levels in rats. Author(s): Houdijk AP, Visser JJ, Rijnsburger ER, Teerlink T, van Leeuwen PA. Source: Clinical Nutrition (Edinburgh, Lothian). 1998 February; 17(1): 11-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10205309&dopt=Abstract
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Dietary L-glutamine supplementation reduces the growth of the Morris Hepatoma 7777 in exercise-trained and sedentary rats. Author(s): Shewchuk LD, Baracos VE, Field CJ. Source: The Journal of Nutrition. 1997 January; 127(1): 158-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9040560&dopt=Abstract
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Does glutamine reduce bacterial translocation? A study in two animal models with impaired gut barrier. Author(s): Foitzik T, Kruschewski M, Kroesen AJ, Hotz HG, Eibl G, Buhr HJ. Source: International Journal of Colorectal Disease. 1999 August; 14(3): 143-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10460904&dopt=Abstract
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Does glutamine supplementation increase radioresistance in squamous cell carcinoma of the cervix? Author(s): Santoso JT, Lucci JA 3rd, Coleman RL, Hatch S, Wong P, Miller D, Mathis JM.
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Early gastrointestinal regulatory peptide response to intestinal resection in the rat is stimulated by enteral glutamine supplementation. Author(s): Wiren M, Adrian TE, Arnelo U, Permert J, Staab P, Larsson J. Source: Digestive Surgery. 1999; 16(3): 197-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10436367&dopt=Abstract
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Effect of carbohydrate supplementation on plasma glutamine during prolonged exercise and recovery. Author(s): van Hall G, Saris WH, Wagenmakers AJ. Source: International Journal of Sports Medicine. 1998 February; 19(2): 82-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9562214&dopt=Abstract
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Effect of enteral supplementation with glutamine on mesenteric blood flow in premature neonates. Author(s): Mercier A, Eurin D, Poulet-Young V, Marret S, Dechelotte P. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 April; 22(2): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12706129&dopt=Abstract
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Effect of glutamine and protein supplementation on exercise-induced decreases in salivary IgA. Author(s): Krzywkowski K, Petersen EW, Ostrowski K, Link-Amster H, Boza J, Halkjaer-Kristensen J, Pedersen BK. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2001 August; 91(2): 832-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11457800&dopt=Abstract
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Effect of glutamine on the intestinal permeability changes induced by indomethacin in humans. Author(s): Hond ED, Peeters M, Hiele M, Bulteel V, Ghoos Y, Rutgeerts P. Source: Alimentary Pharmacology & Therapeutics. 1999 May; 13(5): 679-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10233193&dopt=Abstract
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Effect of glutamine supplement and hepatectomy on DNA and protein synthesis in the remnant liver. Author(s): Yoshida S, Yunoki T, Aoyagi K, Ohta J, Ishibashi N, Noake T, Kakegawa T. Source: The Journal of Surgical Research. 1995 October; 59(4): 475-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7564320&dopt=Abstract
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Effect of glutamine supplementation combined with resistance training in young adults. Author(s): Candow DG, Chilibeck PD, Burke DG, Davison KS, Smith-Palmer T.
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Effect of glutamine supplementation of the diet on tissue protein synthesis rate of glucocorticoid-treated rats. Author(s): Boza JJ, Turini M, Moennoz D, Montigon F, Vuichoud J, Gueissaz N, Gremaud G, Pouteau E, Piguet-Welsch C, Finot PA, Ballevre O. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 January; 17(1): 35-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165886&dopt=Abstract
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Effect of glutamine supplementation on changes in the immune system induced by repeated exercise. Author(s): Rohde T, MacLean DA, Pedersen BK. Source: Medicine and Science in Sports and Exercise. 1998 June; 30(6): 856-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624643&dopt=Abstract
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Effect of glutamine supplementation on exercise-induced changes in lymphocyte function. Author(s): Krzywkowski K, Petersen EW, Ostrowski K, Kristensen JH, Boza J, Pedersen BK. Source: American Journal of Physiology. Cell Physiology. 2001 October; 281(4): C125965. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11546663&dopt=Abstract
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Effect of glutamine supplementation on protein metabolism and glutathione in tumor-bearing rats. Author(s): Yoshida S, Kaibara A, Yamasaki K, Ishibashi N, Noake T, Kakegawa T. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1995 November-December; 19(6): 492-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8748364&dopt=Abstract
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Effect of high dose growth hormone with glutamine and no change in diet on intestinal absorption in short bowel patients: a randomised, double blind, crossover, placebo controlled study. Author(s): Szkudlarek J, Jeppesen PB, Mortensen PB. Source: Gut. 2000 August; 47(2): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10896910&dopt=Abstract
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Effect of L-glutamine supplementation on impaired glucose regulation during intravenous lipid administration. Author(s): Ballard TC, Farag A, Branum GD, Akwari OE, Opara EC.
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Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn's disease. Author(s): Den Hond E, Hiele M, Peeters M, Ghoos Y, Rutgeerts P. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1999 January-February; 23(1): 7-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9888411&dopt=Abstract
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Effect of low- and high-carbohydrate diets on the plasma glutamine and circulating leukocyte responses to exercise. Author(s): Gleeson M, Blannin AK, Walsh NP, Bishop NC, Clark AM. Source: Int J Sport Nutr. 1998 March; 8(1): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9534081&dopt=Abstract
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Effect of oral glutamine supplementation during bone marrow transplantation. Author(s): Coghlin Dickson TM, Wong RM, offrin RS, Shizuru JA, Johnston LJ, Hu WW, Blume KG, Stockerl-Goldstein KE. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 March-April; 24(2): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10772184&dopt=Abstract
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Effect of oral glutamine supplementation on human neutrophil lipopolysaccharidestimulated degranulation following prolonged exercise. Author(s): Walsh NP, Blannin AK, Bishop NC, Robson PJ, Gleeson M. Source: International Journal of Sport Nutrition and Exercise Metabolism. 2000 March; 10(1): 39-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722780&dopt=Abstract
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Effect of parenteral glutamine supplementation on lymphocyte subpopulations in critically ill patients receiving glutamine enriched enteral nutrition. Author(s): Demirag K, Uyar M, Gulbahar O, Kocabas S, Delen Akcay Y, Moral AR. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(S1): S50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14683937&dopt=Abstract
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Effect of parenteral glutamine supplementation on plasma amino acid concentrations in extremely low-birth-weight infants. Author(s): Poindexter BB, Ehrenkranz RA, Stoll BJ, Koch MA, Wright LL, Oh W, Papile LA, Bauer CR, Carlo WA, Donovan EF, Fanaroff AA, Korones SB, Laptook AR, Shankaran S, Stevenson DK, Tyson JE, Lemons JA; National Institute of Child Health and Human Development Neonatal Research Network.
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Effects of diazepam on neutrophil (PMN) free amino acid profiles and immune functions in vitro. Metabolical and immunological consequences of L-alanyl-Lglutamine supplementation. Author(s): Muhling J, Sablotzki A, Fuchs M, Krull M, Dehne MG, Weiss S, Gonter J, Quandt D, Hempelmann G. Source: The Journal of Nutritional Biochemistry. 2001 January; 12(1): 46-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11179861&dopt=Abstract
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Effects of effervescent creatine, ribose, and glutamine supplementation on muscular strength, muscular endurance, and body composition. Author(s): Falk DJ, Heelan KA, Thyfault JP, Koch AJ. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2003 November; 17(4): 810-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14636104&dopt=Abstract
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Effects of glutamine on head and neck squamous cell carcinoma. Author(s): Erickson R, Ross D, Medina J. Source: Otolaryngology and Head and Neck Surgery. 1999 October; 121(4): 348-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10504586&dopt=Abstract
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Effects of glutamine supplementation of an amino acid-based purified diet on intestinal mucosal integrity in cats with methotrexate-induced enteritis. Author(s): Marks SL, Cook AK, Reader R, Kass PH, Theon AP, Greve C, Rogers QR. Source: Am J Vet Res. 1999 June; 60(6): 755-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10376908&dopt=Abstract
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Effects of glutamine supplementation on circulating lymphocytes after bone marrow transplantation: a pilot study. Author(s): Ziegler TR, Bye RL, Persinger RL, Young LS, Antin JH, Wilmore DW. Source: The American Journal of the Medical Sciences. 1998 January; 315(1): 4-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9427568&dopt=Abstract
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Effects of glutamine supplementation on innate immune response in rats with gutderived sepsis. Author(s): Yeh SL, Lai YN, Shang HF, Lin MT, Chen WJ. Source: The British Journal of Nutrition. 2004 March; 91(3): 423-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=15005828&dopt=Abstract
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Effects of glutamine supplementation, GH, and IGF-I on glutamine metabolism in critically ill patients.
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Effects of glutamine supplements and radiochemotherapy on systemic immune and gut barrier function in patients with advanced esophageal cancer. Author(s): Yoshida S, Matsui M, Shirouzu Y, Fujita H, Yamana H, Shirouzu K. Source: Annals of Surgery. 1998 April; 227(4): 485-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9563534&dopt=Abstract
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Effects of growth hormone (rhGH) and glutamine supplemented parenteral nutrition on intestinal adaptation in short bowel rats. Author(s): Gu Y, Wu ZH, Xie JX, Jin DY, Zhuo HC. Source: Clinical Nutrition (Edinburgh, Lothian). 2001 April; 20(2): 159-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11327744&dopt=Abstract
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Effects of n-3 fatty acid, fructose-1,6-diphosphate and glutamine on mucosal cell proliferation and apoptosis of small bowel graft after transplantation in rats. Author(s): Wu XT, Li JS, Zhao XF, Li N, Ma YK, Zhuang W, Zhou Y, Yang G. Source: World Journal of Gastroenterology : Wjg. 2003 June; 9(6): 1323-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800249&dopt=Abstract
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Effects of oral arginine and glutamine on radiation-induced injury in the rat. Author(s): Hwang JM, Chan DC, Chang TM, Tsao TY, Tsou SS, Lu RH, Tsai LM. Source: The Journal of Surgical Research. 2003 February; 109(2): 149-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12643857&dopt=Abstract
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Effects of oral supplement of L-glutamine on diverted colon wall. Author(s): Paulo FL. Source: Journal of Cellular and Molecular Medicine. 2002 July-September; 6(3): 377-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417053&dopt=Abstract
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Effects of parenteral alanine-glutamine supplementation on the rat nutritional condition. Author(s): Ortiz de Urbina JJ, Jorquera F, Villares C, Culebras J, Gonzalez P, GonzalezGallego J, Tunon MJ. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(S1): S31-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14683865&dopt=Abstract
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Effects on skeletal muscle of intravenous glutamine supplementation to ICU patients. Author(s): Tjader I, Rooyackers O, Forsberg AM, Vesali RF, Garlick PJ, Wernerman J.
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Enteral alanyl-glutamine supplement promotes intestinal adaptation in rats. Author(s): Satoh J, Tsujikawa T, Fujiyama Y, Banba T. Source: International Journal of Molecular Medicine. 2003 October; 12(4): 615-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12964044&dopt=Abstract
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Enteral glutamine supplementation and dexamethasone attenuate the local intestinal damage in rats with experimental necrotizing enterocolitis. Author(s): Dilsiz A, Ciftci I, Aktan TM, Gurbilek M, Karagozoglu E. Source: Pediatric Surgery International. 2003 October; 19(8): 578-82. Epub 2003 October 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14556027&dopt=Abstract
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Enteral glutamine supplementation and morbidity in low birth weight infants. Author(s): Vaughn P, Thomas P, Clark R, Neu J. Source: The Journal of Pediatrics. 2003 June; 142(6): 662-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12838195&dopt=Abstract
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Enteral glutamine supplementation for the very low birthweight infant: plasma amino acid concentrations. Author(s): Roig JC, Meetze WH, Auestad N, Jasionowski T, Veerman M, McMurray CA, Neu J. Source: The Journal of Nutrition. 1996 April; 126(4 Suppl): 1115S-20S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8642443&dopt=Abstract
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Enteral glutamine supplementation for very low birth weight infants decreases morbidity. Author(s): Neu J, Roig JC, Meetze WH, Veerman M, Carter C, Millsaps M, Bowling D, Dallas MJ, Sleasman J, Knight T, Auestad N. Source: The Journal of Pediatrics. 1997 November; 131(5): 691-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9403648&dopt=Abstract
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Enteral glutamine supplementation for very-low-birth-weight infants decreases hospital costs. Author(s): Dallas MJ, Bowling D, Roig JC, Auestad N, Neu J. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1998 November-December; 22(6): 352-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9829607&dopt=Abstract
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Expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), and Bcl-2 protooncogene protein by Muller (glial) cells in retinal light damage of rats. Author(s): Grosche J, Hartig W, Reichenbach A. Source: Neuroscience Letters. 1995 February 9; 185(2): 119-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7746501&dopt=Abstract
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Functional importance of Asp56 from the alpha-polypeptide of Phaseolus vulgaris glutamine synthetase. An essential residue for transferase but not for biosynthetic enzyme activity. Author(s): Clemente MT, Marquez AJ. Source: European Journal of Biochemistry / Febs. 1999 September; 264(2): 453-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10491091&dopt=Abstract
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Glucocorticoids play an important role in mediating the enhanced metabolism of arginine and glutamine in enterocytes of postweaning pigs. Author(s): Flynn NE, Wu G. Source: The Journal of Nutrition. 1997 May; 127(5): 732-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9164994&dopt=Abstract
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Glucose, galactose, and glutamine metabolism in pig isolated enterocytes during development. Author(s): Darcy-Vrillon B, Posho L, Morel MT, Bernard F, Blachier F, Meslin JC, Duee PH. Source: Pediatric Research. 1994 August; 36(2): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7970931&dopt=Abstract
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Glutamate in enteral nutrition: can glutamate replace glutamine in supplementation to enteral nutrition in burned rats? Author(s): Hasebe M, Suzuki H, Mori E, Furukawa J, Kobayashi K, Ueda Y. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1999 September-October; 23(5 Suppl): S78-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483902&dopt=Abstract
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Glutamine alimentation in catabolic state. Author(s): Boelens PG, Nijveldt RJ, Houdijk AP, Meijer S, van Leeuwen PA. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2569S-77S; Discussion 2590S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533315&dopt=Abstract
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Glutamine and arginine: immunonutrients for improved health. Author(s): Field CJ, Johnson I, Pratt VC.
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Glutamine and cancer. Author(s): Medina MA. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2539S-42S; Discussion 2550S-1S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533309&dopt=Abstract
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Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high-dose chemotherapy. Author(s): Goringe AP, Brown S, O'Callaghan U, Rees J, Jebb S, Elia M, Poynton CH. Source: Bone Marrow Transplantation. 1998 April; 21(8): 829-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9603409&dopt=Abstract
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Glutamine and wound healing. Author(s): Collins N. Source: Advances in Skin & Wound Care. 2002 September-October; 15(5): 233-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368714&dopt=Abstract
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Glutamine effects on permeability and ATP content of jejunal mucosa in starved rats. Author(s): Yang H, Soderholm J, Larsson J, Permert J, Olaison G, Lindgren J, Wiren M. Source: Clinical Nutrition (Edinburgh, Lothian). 1999 October; 18(5): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10601538&dopt=Abstract
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Glutamine for irinotecan diarrhea. Author(s): Savarese D, Al-Zoubi A, Boucher J. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2000 January; 18(2): 450-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10637264&dopt=Abstract
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Glutamine for the gut: mystical properties or an ordinary amino acid? Author(s): Buchman AL. Source: Current Gastroenterology Reports. 1999 October; 1(5): 417-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10980981&dopt=Abstract
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Glutamine in pediatrics: where next? Author(s): Ball PA, Hardy G. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 June; 18(6): 451-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044814&dopt=Abstract
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Glutamine metabolism stimulates intestinal cell MAPKs by a cAMP-inhibitable, Rafindependent mechanism. Author(s): Rhoads JM, Argenzio RA, Chen W, Graves LM, Licato LL, Blikslager AT, Smith J, Gatzy J, Brenner DA. Source: Gastroenterology. 2000 January; 118(1): 90-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10611157&dopt=Abstract
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Glutamine parenteral supplementation in stem cell transplant. Author(s): Piccirillo N, De Matteis S, Sora F, Laurenti L, Chiusolo P, Leone G, Sica S. Source: Bone Marrow Transplantation. 2004 February; 33(4): 455; Author Reply 457. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14676779&dopt=Abstract
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Glutamine supplementation and deprivation: effect on artificially reared rat small intestinal morphology. Author(s): Potsic B, Holliday N, Lewis P, Samuelson D, DeMarco V, Neu J. Source: Pediatric Research. 2002 September; 52(3): 430-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193680&dopt=Abstract
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Glutamine supplementation and GH/IGF-I treatment in critically ill patients: effects on glutamine metabolism and protein balance. Author(s): Umpleby AM, Carroll PV, Russell-Jones DL, Treacher DF, Jackson NC. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 February; 18(2): 127-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844642&dopt=Abstract
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Glutamine supplementation and intestinal permeability in Crohn's disease. Author(s): Akobeng AK, Miller V, Thomas AG, Richmond K. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 May-June; 24(3): 196. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850950&dopt=Abstract
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Glutamine supplementation does not prevent bacterial translocation after non-lethal haemorrhage in rats. Author(s): Bark T, Katouli M, Ljungquist O, Mollby R, Svenberg T. Source: The European Journal of Surgery = Acta Chirurgica. 1995 January; 161(1): 3-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7727603&dopt=Abstract
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Glutamine supplementation enhances mucosal immunity in rats with Gut-Derived sepsis. Author(s): Lai YN, Yeh SL, Lin MT, Shang HF, Yeh CL, Chen WJ. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2004 March; 20(3): 286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14990270&dopt=Abstract
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Glutamine supplementation fails to affect muscle protein kinetics in critically ill patients. Author(s): Gore DC, Wolfe RR. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2002 November-December; 26(6): 342-9; Discussion 349-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12405645&dopt=Abstract
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Glutamine supplementation for low-birth-weight and very low-birth-weight infants. Author(s): Wu PY. Source: Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi. 1998 March-April; 39(2): 7881. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9599893&dopt=Abstract
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Glutamine supplementation for preventing morbidity in preterm infants. Author(s): Tubman TR, Thompson SW. Source: Cochrane Database Syst Rev. 2000; (2): Cd001457. Review. Update In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796267&dopt=Abstract
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Glutamine supplementation for prevention of morbidity in preterm infants. Author(s): Tubman TR, Thompson SW. Source: Cochrane Database Syst Rev. 2001; (4): Cd001457. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11687112&dopt=Abstract
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Glutamine supplementation further enhances exercise-induced plasma IL-6. Author(s): Hiscock N, Petersen EW, Krzywkowski K, Boza J, Halkjaer-Kristensen J, Pedersen BK. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 July; 95(1): 145-8. Epub 2003 February 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611772&dopt=Abstract
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Glutamine supplementation in artificial nutritional support. Author(s): Powell-Tuck J. Source: Lancet. 1997 August 23; 350(9077): 534. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9284773&dopt=Abstract
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Glutamine supplementation in bone marrow transplantation. Author(s): Ziegler TR. Source: The British Journal of Nutrition. 2002 January; 87 Suppl 1: S9-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11895159&dopt=Abstract
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Glutamine supplementation in cancer patients transplantation and high dose chemotherapy. Author(s): Ziegler TR.
receiving
bone
marrow
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Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2578S-84S; Discussion 2590S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533316&dopt=Abstract •
Glutamine supplementation in cancer patients receiving chemotherapy: a doubleblind randomized study. Author(s): Bozzetti F, Biganzoli L, Gavazzi C, Cappuzzo F, Carnaghi C, Buzzoni R, Dibartolomeo M, Baietta E. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1997 July-August; 13(7-8): 74851. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9263281&dopt=Abstract
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Glutamine supplementation in cancer patients. Author(s): Yoshida S, Kaibara A, Ishibashi N, Shirouzu K. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2001 September; 17(9): 766-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527675&dopt=Abstract
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Glutamine supplementation in catabolic illness. Author(s): Ziegler TR. Source: The American Journal of Clinical Nutrition. 1996 October; 64(4): 645-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8839515&dopt=Abstract
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Glutamine supplementation in catabolic patients. Author(s): Sacks GS. Source: The Annals of Pharmacotherapy. 1999 March; 33(3): 348-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200861&dopt=Abstract
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Glutamine supplementation in critically ill and elective surgical patients: does the evidence warrant its use? Author(s): Miskovitz P. Source: Critical Care Medicine. 2002 September; 30(9): 2152-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352061&dopt=Abstract
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Glutamine supplementation in low-birth-weight infants: mechanisms of action. Author(s): Neu J, DeMarco V, Weiss M. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1999 September-October; 23(5 Suppl): S49-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483895&dopt=Abstract
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Glutamine supplementation in serious illness: a systematic review of the evidence. Author(s): Novak F, Heyland DK, Avenell A, Drover JW, Su X.
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Source: Critical Care Medicine. 2002 September; 30(9): 2022-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352035&dopt=Abstract •
Glutamine supplementation in vitro and in vivo, in exercise and in immunodepression. Author(s): Castell L. Source: Sports Medicine (Auckland, N.Z.). 2003; 33(5): 323-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12696982&dopt=Abstract
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Glutamine supplementation is safe in home parenteral nutrition (HPN). Author(s): Culkin A, Gabe SM, Forbes A, Chadwick C. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(S1): S89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684083&dopt=Abstract
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Glutamine supplementation maintains intramuscular glutamine concentrations and normalizes lymphocyte function in infected early weaned pigs. Author(s): Yoo SS, Field CJ, McBurney MI. Source: The Journal of Nutrition. 1997 November; 127(11): 2253-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9349855&dopt=Abstract
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Glutamine supplementation of enteral nutrition: impact on whole body protein kinetics and glucose metabolism in critically ill patients. Author(s): Long CL, Nelson KM, DiRienzo DB, Weis JK, Stahl RD, Broussard TD, Theus WL, Clark JA, Pinson TW, Geiger JW, et al. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1995 November-December; 19(6): 470-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8748361&dopt=Abstract
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Glutamine supplementation prevents the decrease of mitogen response after a treadmill exercise in rats. Author(s): Moriguchi S, Miwa H, Kishino Y. Source: J Nutr Sci Vitaminol (Tokyo). 1995 February; 41(1): 115-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7616318&dopt=Abstract
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Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle. Author(s): Bruce M, Constantin-Teodosiu D, Greenhaff PL, Boobis LH, Williams C, Bowtell JL. Source: American Journal of Physiology. Endocrinology and Metabolism. 2001 April; 280(4): E669-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254475&dopt=Abstract
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Glutamine supplementation. Heal the gut, help the patient. Author(s): Savy GK. Source: Journal of Infusion Nursing : the Official Publication of the Infusion Nurses Society. 2002 January-February; 25(1): 65-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840007&dopt=Abstract
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Glutamine supplements in premature infants: why and how. Author(s): Neu J. Source: Journal of Pediatric Gastroenterology and Nutrition. 2003 November; 37(5): 5335. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14581791&dopt=Abstract
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Glutamine synthetase activity in Solanaceous cell suspensions accumulating alkaloids or not. 13C NMR and enzymatic assay. Author(s): Mesnard F, Marty D, Gillet-Manceau F, Fliniaux MA, Monti JP. Source: Comptes Rendus De L'academie Des Sciences. Serie Iii, Sciences De La Vie. 1999 September; 322(9): 743-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10547716&dopt=Abstract
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Glutamine synthetase from N2-fixing cyanobacterium Nostoc muscorum-purification, biochemical and immunological characteristics. Author(s): Srivastava R, Amla DV. Source: Indian J Exp Biol. 1997 October; 35(10): 1098-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475046&dopt=Abstract
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Glutamine to intensive care unit patients. Author(s): Wernerman J. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 July-August; 27(4): 302-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903897&dopt=Abstract
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Glutamine transport in rat brain synaptic and non-synaptic mitochondria. Author(s): Roberg B, Torgner IA, Kvamme E. Source: Neurochemical Research. 1999 March; 24(3): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215512&dopt=Abstract
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Glutamine treatment of paclitaxel-induced myalgias and arthralgias. Author(s): Savarese D, Boucher J, Corey B. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 December; 16(12): 3918-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9850043&dopt=Abstract
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Glutamine, myo-inositol, and organic brain osmolytes after portocaval anastomosis in the rat: implications for ammonia-induced brain edema. Author(s): Cordoba J, Gottstein J, Blei AT. Source: Hepatology (Baltimore, Md.). 1996 October; 24(4): 919-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8855198&dopt=Abstract
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Glutamine. Author(s): Heys SD, Ashkanani F. Source: The British Journal of Surgery. 1999 March; 86(3): 289-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10201766&dopt=Abstract
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Glutamine: a potentially useful supplement for athletes. Author(s): Antonio J, Street C. Source: Canadian Journal of Applied Physiology = Revue Canadienne De Physiologie Appliquee. 1999 February; 24(1): 1-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9916176&dopt=Abstract
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Glutamine-antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Author(s): Shabert JK, Winslow C, Lacey JM, Wilmore DW. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1999 November-December; 15(11-12): 860-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10575661&dopt=Abstract
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Glutamine-enhanced nutrition in the critically ill patient. Author(s): Andrews F, Griffiths R. Source: Hosp Med. 2002 March; 63(3): 144-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11933816&dopt=Abstract
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Glutamine-supplemented tube feedings versus total parenteral nutrition in children receiving intensive chemotherapy. Author(s): Ford C, Whitlock JA, Pietsch JB. Source: Journal of Pediatric Oncology Nursing : Official Journal of the Association of Pediatric Oncology Nurses. 1997 April; 14(2): 68-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9144976&dopt=Abstract
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Glutathione stimulates A549 cell proliferation in glutamine-deficient culture: the effect of glutamate supplementation. Author(s): Kang YJ, Feng Y, Hatcher EL. Source: Journal of Cellular Physiology. 1994 December; 161(3): 589-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7962140&dopt=Abstract
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Growth hormone, glutamine, and a modified diet enhance nutrient absorption in patients with severe short bowel syndrome. Author(s): Byrne TA, Morrissey TB, Nattakom TV, Ziegler TR, Wilmore DW. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1995 July-August; 19(4): 296302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8523629&dopt=Abstract
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Gut glutamine metabolism at different stages of sepsis in rats. Author(s): Nose K, Wasa M, Okada A. Source: Surgery Today. 2002; 32(8): 695-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12181719&dopt=Abstract
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Identification of several soybean cytosolic glutamine synthetase transcripts highly or specifically expressed in nodules: expression studies using one of the corresponding genes in transgenic Lotus corniculatus. Author(s): Marsolier MC, Debrosses G, Hirel B. Source: Plant Molecular Biology. 1995 January; 27(1): 1-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7865779&dopt=Abstract
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Immunosuppression in undernourished rats: the effect of glutamine supplementation. Author(s): Cunha WD, Friedler G, Vaisberg M, Egami MI, Costa Rosa LF. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 October; 22(5): 453-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14512032&dopt=Abstract
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Impact of oral L-glutamine on glutathione, glutamine, and glutamate blood levels in volunteers. Author(s): Valencia E, Marin A, Hardy G. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2002 May; 18(5): 367-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11985937&dopt=Abstract
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Increased circulating B and T lymphocyte in burn patients given enteral glutamine supplement. Author(s): Garrel DR, Bernier J. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(S1): S38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14683893&dopt=Abstract
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Influence of divalent cations on the catalytic properties and secondary structure of unadenylylated glutamine synthetase from Azospirillum brasilense. Author(s): Antonyuk LP, Smirnova VE, Kamnev AA, Serebrennikova OB, Vanoni MA, Zanetti G, Kudelina IA, Sokolov OI, Ignatov VV.
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Source: Biometals : an International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine. 2001 March; 14(1): 13-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11368271&dopt=Abstract •
Involvement of glutamine, arginine, and polyamines in the action of ornithine alphaketoglutarate on macrophage functions in stressed rats. Author(s): Moinard C, Caldefie F, Walrand S, Felgines C, Vasson MP, Cynober L. Source: Journal of Leukocyte Biology. 2000 June; 67(6): 834-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10857856&dopt=Abstract
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L-glutamine supplementation improves nelfinavir-associated diarrhea in HIVinfected individuals. Author(s): Huffman FG, Walgren ME. Source: Hiv Clinical Trials. 2003 September-October; 4(5): 324-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583848&dopt=Abstract
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L-glutamine supplementation in home total parenteral nutrition patients: stability, safety, and effects on intestinal absorption. Author(s): Hornsby-Lewis L, Shike M, Brown P, Klang M, Pearlstone D, Brennan MF. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1994 May-June; 18(3): 268-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8065004&dopt=Abstract
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L-glutamine supplementation of a high fat diet reduces body weight and attenuates hyperglycemia and hyperinsulinemia in C57BL/6J mice. Author(s): Opara EC, Petro A, Tevrizian A, Feinglos MN, Surwit RS. Source: The Journal of Nutrition. 1996 January; 126(1): 273-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8558312&dopt=Abstract
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Low serum concentrations of insulin-like growth factor-I in children with active Crohn disease: effect of enteral nutritional support and glutamine supplementation. Author(s): Akobeng AI, Clayton PE, Miller V, Hall CM, Thomas AG. Source: Scandinavian Journal of Gastroenterology. 2002 December; 37(12): 1422-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523592&dopt=Abstract
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Luminal glutamine perfusion alters endotoxin-related changes in ileal permeability of the piglet. Author(s): Dugan ME, McBurney MI. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1995 January-February; 19(1): 83-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7658607&dopt=Abstract
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Mechanisms of glutamine transport in rat adipocytes and acute regulation by cell swelling.
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Author(s): Ritchie JW, Baird FE, Christie GR, Stewart A, Low SY, Hundal HS, Taylor PM. Source: Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2001; 11(5): 259-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11684815&dopt=Abstract •
Metabolic and immune effects of dietary arginine, glutamine and omega-3 fatty acids supplementation in immunocompromised patients. Author(s): Chuntrasakul C, Siltharm S, Sarasombath S, Sittapairochana C, Leowattana W, Chockvivatanavanit S, Bunnak A. Source: J Med Assoc Thai. 1998 May; 81(5): 334-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9623033&dopt=Abstract
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Metabolic regulation of the gene encoding glutamine-dependent asparagine synthetase in Arabidopsis thaliana. Author(s): Lam HM, Peng SS, Coruzzi GM. Source: Plant Physiology. 1994 December; 106(4): 1347-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7846154&dopt=Abstract
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Metabolic response of muscle to alanine, glutamine, and valine supplementation during severe illness. Author(s): Gore DC, Wolfe RR. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 September-October; 27(5): 307-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12971729&dopt=Abstract
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NAC, glutamine, and alpha lipoic acid. Interview by John S. James. Author(s): Lands L. Source: Aids Treat News. 1997 April 4; (No 268): 2-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11364196&dopt=Abstract
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Neither glutamine nor arginine supplementation of diets increase glutamine body stores in healthy growing rats. Author(s): Boza JJ, Moennoz D, Jarret AR, Vuichoud J, Garcia-Rodenas C, Finot PA, Ballevre O. Source: Clinical Nutrition (Edinburgh, Lothian). 2000 October; 19(5): 319-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11031069&dopt=Abstract
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Nitrogen metabolism in actinorhizal nodules of Alnus glutinosa: expression of glutamine synthetase and acetylornithine transaminase. Author(s): Guan C, Ribeiro A, Akkermans AD, Jing Y, van Kammen A, Bisseling T, Pawlowski K.
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No differences in mucosal adaptive growth one week after intestinal resection in rats given enteral glutamine supplementation or deprived of glutamine. Author(s): Wiren ME, Permert J, Skullman SP, Wang F, Larsson J. Source: The European Journal of Surgery = Acta Chirurgica. 1996 June; 162(6): 489-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8817227&dopt=Abstract
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No effect of bolus glutamine supplementation on the postresectional adaptation of small bowel mucosa in rats receiving chow ad libitum. Author(s): Yang H, Larsson J, Permert J, Braaf Y, Wiren M. Source: Digestive Surgery. 2000; 17(3): 256-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10867459&dopt=Abstract
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Nutrients and HIV: part three - N-acetylcysteine, alpha-lipoic acid, L-glutamine, and L-carnitine. Author(s): Patrick L. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2000 August; 5(4): 290-305. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10956377&dopt=Abstract
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Nutritional benefits of enteral alanyl-glutamine supplementation on rat small intestinal damage induced by cyclophosphamide. Author(s): Satoh J, Tsujikawa T, Fujiyama Y, Bamba T. Source: Journal of Gastroenterology and Hepatology. 2003 June; 18(6): 719-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12753156&dopt=Abstract
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Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, doubleblind, placebo-controlled study. Author(s): Clark RH, Feleke G, Din M, Yasmin T, Singh G, Khan FA, Rathmacher JA. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2000 May-June; 24(3): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850936&dopt=Abstract
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Oral glutamine (AES-14) supplementation inhibits PI-3k/Akt signaling in experimental breast cancer. Author(s): Todorova VK, Harms SA, Luo S, Kaufmann Y, Babb KB, Klimberg VS. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 November-December; 27(6): 404-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14621121&dopt=Abstract
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Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Author(s): Cockerham MB, Weinberger BB, Lerchie SB. Source: The Annals of Pharmacotherapy. 2000 March; 34(3): 300-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917373&dopt=Abstract
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Oral glutamine supplements in autologous hematopoietic transplant: impact on gastrointestinal toxicity and plasma protein levels. Author(s): Canovas G, Leon-Sanz M, Gomez P, Valero MA, Gomis P, La Huerta JJ. Source: Haematologica. 2000 November; 85(11): 1229-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11064482&dopt=Abstract
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Oral glutamine to prevent chemotherapy induced stomatitis: a pilot study. Author(s): Skubitz KM, Anderson PM. Source: The Journal of Laboratory and Clinical Medicine. 1996 February; 127(2): 223-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8636652&dopt=Abstract
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Oral L-glutamine therapy for sickle cell anemia: I. Subjective clinical improvement and favorable change in red cell NAD redox potential. Author(s): Niihara Y, Zerez CR, Akiyama DS, Tanaka KR. Source: American Journal of Hematology. 1998 June; 58(2): 117-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9625578&dopt=Abstract
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Organization and expression of genes in the genomic region surrounding the glutamine synthetase gene Gln1 from Lotus japonicus. Author(s): Thykjaer T, Danielsen D, She Q, Stougaard J. Source: Molecular & General Genetics : Mgg. 1997 August; 255(6): 628-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9323367&dopt=Abstract
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Outcome of critically ill patients after supplementation with glutamine. Author(s): Griffiths RD. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1997 July-August; 13(7-8): 7524. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9263282&dopt=Abstract
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Overexpression of the complementary DNA for human glutamine:fructose-6phosphate amidotransferase in mesangial cells enhances glucose-induced fibronectin synthesis and transcription factor cyclic adenosine monophosphate-responsive element binding phosphorylation. Author(s): Singh LP, Alexander M, Greene K, Crook ED.
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Oxidative inactivation of glutamine synthetase from the cyanobacterium Anabaena variabilis. Author(s): Martin G, Haehnel W, Boger P. Source: Journal of Bacteriology. 1997 February; 179(3): 730-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9006027&dopt=Abstract
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Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapyinduced toxicity. Author(s): van Zaanen HC, van der Lelie H, Timmer JG, Furst P, Sauerwein HP. Source: Cancer. 1994 November 15; 74(10): 2879-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7954251&dopt=Abstract
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Peroxynitrite-mediated nitration of tyrosine residues in Escherichia coli glutamine synthetase mimics adenylylation: relevance to signal transduction. Author(s): Berlett BS, Friguet B, Yim MB, Chock PB, Stadtman ER. Source: Proceedings of the National Academy of Sciences of the United States of America. 1996 March 5; 93(5): 1776-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8700834&dopt=Abstract
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Pilot study with a glutamine-supplemented enteral formula in critically ill infants. Author(s): Barbosa E, Moreira EA, Goes JE, Faintuch J. Source: Revista Do Hospital Das Clinicas. 1999 January-February; 54(1): 21-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10488597&dopt=Abstract
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Plasma amino acid levels in children with sickle cell disease receiving an oral glutamine supplement. Author(s): Storm MC, Helms RA, Williams R, Olivi S, Li C, Wang WC. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(S1): S73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14684022&dopt=Abstract
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Plasma taurine concentrations increase after enteral glutamine supplementation in trauma patients and stressed rats. Author(s): Boelens PG, Houdijk AP, de Thouars HN, Teerlink T, van Engeland MI, Haarman HJ, van Leeuwen PA. Source: The American Journal of Clinical Nutrition. 2003 January; 77(1): 250-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499349&dopt=Abstract
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Prevention of chemotherapy and radiation toxicity with glutamine. Author(s): Savarese DM, Savy G, Vahdat L, Wischmeyer PE, Corey B.
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Source: Cancer Treatment Reviews. 2003 December; 29(6): 501-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585260&dopt=Abstract •
Prevention of muscle function impairment by glutamine supplementation during systemic inflammation. Author(s): Maglara A, McArdle A, Griffiths RD, Jackson MJ. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 August; 22(S1): S32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14683871&dopt=Abstract
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Prolonged dietary treatment with conjugated linoleic acid stimulates porcine muscle peroxisome proliferator activated receptor gamma and glutamine-fructose aminotransferase gene expression in vivo. Author(s): Meadus WJ, MacInnis R, Dugan ME. Source: Journal of Molecular Endocrinology. 2002 April; 28(2): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11932205&dopt=Abstract
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Prophylactic effect of dietary glutamine supplementation on interleukin 8 and tumour necrosis factor alpha production in trinitrobenzene sulphonic acid induced colitis. Author(s): Ameho CK, Adjei AA, Harrison EK, Takeshita K, Morioka T, Arakaki Y, Ito E, Suzuki I, Kulkarni AD, Kawajiri A, Yamamoto S. Source: Gut. 1997 October; 41(4): 487-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9391247&dopt=Abstract
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Rapid aggregate formation of the huntingtin N-terminal fragment carrying an expanded polyglutamine tract. Author(s): Hazeki N, Nakamura K, Goto J, Kanazawa I. Source: Biochemical and Biophysical Research Communications. 1999 March 16; 256(2): 361-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10079189&dopt=Abstract
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Reduction of chemotherapy-induced side-effects by parenteral glutamine supplementation in patients with metastatic colorectal cancer. Author(s): Decker-Baumann C, Buhl K, Frohmuller S, von Herbay A, Dueck M, Schlag PM. Source: European Journal of Cancer (Oxford, England : 1990). 1999 February; 35(2): 2027. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10448260&dopt=Abstract
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Reduction of paclitaxel-induced peripheral neuropathy with glutamine. Author(s): Vahdat L, Papadopoulos K, Lange D, Leuin S, Kaufman E, Donovan D, Frederick D, Bagiella E, Tiersten A, Nichols G, Garrett T, Savage D, Antman K, Hesdorffer CS, Balmaceda C.
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Source: Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. 2001 May; 7(5): 1192-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11350883&dopt=Abstract •
Regulation of glutamine:fructose-6-phosphate amidotransferase by cAMP-dependent protein kinase. Author(s): Zhou J, Huynh QK, Hoffman RT, Crook ED, Daniels MC, Gulve EA, McClain DA. Source: Diabetes. 1998 December; 47(12): 1836-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9836513&dopt=Abstract
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Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine. Author(s): May PE, Barber A, D'Olimpio JT, Hourihane A, Abumrad NN. Source: American Journal of Surgery. 2002 April; 183(4): 471-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11975938&dopt=Abstract
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Role of L-glutamine in critical illness: new insights. Author(s): Kelly D, Wischmeyer PE. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2003 March; 6(2): 21722. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589192&dopt=Abstract
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Site-directed mutagenesis of Glu-297 from the alpha-polypeptide of Phaseolus vulgaris glutamine synthetase alters kinetic and structural properties and confers resistance to L-methionine sulfoximine. Author(s): Clemente MT, Marquez AJ. Source: Plant Molecular Biology. 1999 July; 40(5): 835-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10487218&dopt=Abstract
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Some aspects of the acute phase response after a marathon race, and the effects of glutamine supplementation. Author(s): Castell LM, Poortmans JR, Leclercq R, Brasseur M, Duchateau J, Newsholme EA. Source: European Journal of Applied Physiology and Occupational Physiology. 1997; 75(1): 47-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9007457&dopt=Abstract
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Special feature for the Olympics: effects of exercise on the immune system: modification of immune responses to exercise by carbohydrate, glutamine and antioxidant supplements. Author(s): Gleeson M, Bishop NC.
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Source: Immunology and Cell Biology. 2000 October; 78(5): 554-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11050539&dopt=Abstract •
Standardized parenteral alanyl-glutamine dipeptide supplementation is not beneficial in autologous transplant patients: a randomized, double-blind, placebo controlled study. Author(s): Pytlik R, Benes P, Patorkova M, Chocenska E, Gregora E, Prochazka B, Kozak T. Source: Bone Marrow Transplantation. 2002 December; 30(12): 953-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476290&dopt=Abstract
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The effect of enteral glutamine deprivation and supplementation on the structure of rat small-intestine mucosa during a systemic injury response. Author(s): Wusteman M, Tate H, Weaver L, Austin S, Neale G, Elia M. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 1995 January-February; 19(1): 22-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7658595&dopt=Abstract
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The effect of glutamine supplementation in patients following elective surgery and accidental injury. Author(s): Wilmore DW. Source: The Journal of Nutrition. 2001 September; 131(9 Suppl): 2543S-9S; Discussion 2550S-1S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533310&dopt=Abstract
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The effect of supplemental enteral glutamine on plasma levels, gut function, and outcome in severe burns: a randomized, double-blind, controlled clinical trial. Author(s): Zhou YP, Jiang ZM, Sun YH, Wang XR, Ma EL, Wilmore D. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2003 July-August; 27(4): 241-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12903886&dopt=Abstract
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The effects of 8 weeks of creatine monohydrate and glutamine supplementation on body composition and performance measures. Author(s): Lehmkuhl M, Malone M, Justice B, Trone G, Pistilli E, Vinci D, Haff EE, Kilgore JL, Haff GG. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2003 August; 17(3): 425-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12930166&dopt=Abstract
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The effects of glutamine-supplemented diet on the intestinal mucosa of the malnourished growing rat. Author(s): Tannuri U, Carrazza FR, Iriya K.
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Source: Revista Do Hospital Das Clinicas. 2000 May-June; 55(3): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983011&dopt=Abstract •
The effects of high-dose glutamine ingestion on weightlifting performance. Author(s): Antonio J, Sanders MS, Kalman D, Woodgate D, Street C. Source: Journal of Strength and Conditioning Research / National Strength & Conditioning Association. 2002 February; 16(1): 157-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834123&dopt=Abstract
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The effects of oral glutamine supplementation on athletes after prolonged, exhaustive exercise. Author(s): Castell LM, Newsholme EA. Source: Nutrition (Burbank, Los Angeles County, Calif.). 1997 July-August; 13(7-8): 73842. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9263279&dopt=Abstract
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The role of dietary supplementation with L-glutamine in inflammatory mediator release and intestinal injury in hypoxia/reoxygenation-induced experimental necrotizing enterocolitis. Author(s): Akisu M, Baka M, Huseyinov A, Kultursay N. Source: Annals of Nutrition & Metabolism. 2003; 47(6): 262-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14520021&dopt=Abstract
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The spontaneous induction of glutamine synthetase in pig hepatocytes cocultured with RL-ET-14 cells is completely inhibited by trijodothyronine and okadaic acid. Author(s): Gebhardt R, Schuler M, Schorner D. Source: Biochemical and Biophysical Research Communications. 1998 May 29; 246(3): 895-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9618308&dopt=Abstract
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Therapeutic considerations of L-glutamine: a review of the literature. Author(s): Miller AL. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 1999 August; 4(4): 239-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468648&dopt=Abstract
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Total parenteral nutrition supplementation with glutamine improves survival after gut ischemia/reperfusion. Author(s): Ikeda S, Zarzaur BL, Johnson CD, Fukatsu K, Kudsk KA. Source: Jpen. Journal of Parenteral and Enteral Nutrition. 2002 May-June; 26(3): 169-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12005457&dopt=Abstract
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TPN decreases IL-4 and IL-10 mRNA expression in lipopolysaccharide stimulated intestinal lamina propria cells but glutamine supplementation preserves the expression. Author(s): Fukatsu K, Kudsk KA, Zarzaur BL, Wu Y, Hanna MK, DeWitt RC. Source: Shock (Augusta, Ga.). 2001 April; 15(4): 318-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11303733&dopt=Abstract
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Where is the glutamine? Intradialytic supplementation may not solve all issues in amino acid balance. Author(s): Solomons NW, Stehle P, Furst P. Source: The American Journal of Clinical Nutrition. 2000 November; 72(5): 1236-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063458&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to glutamine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Abdominal Wall Inflammation Source: Integrative Medicine Communications; www.drkoop.com
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AIDS and HIV Source: Integrative Medicine Communications; www.drkoop.com Alcohol Withdrawal Source: Healthnotes, Inc.; www.healthnotes.com Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Arthritis Source: Integrative Medicine Communications; www.drkoop.com Athletic Performance Source: Healthnotes, Inc.; www.healthnotes.com Attention Deficit Disorder Source: Prima Communications, Inc.www.personalhealthzone.com Autoimmune Conditions Source: Integrative Medicine Communications; www.drkoop.com Bone Cancer Source: Integrative Medicine Communications; www.drkoop.com Burns Source: Integrative Medicine Communications; www.drkoop.com Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Connective Tissue Diseases Source: Integrative Medicine Communications; www.drkoop.com Crohn's Disease Source: Integrative Medicine Communications; www.drkoop.com Diarrhea Source: Integrative Medicine Communications; www.drkoop.com Digestive Disorders Source: Integrative Medicine Communications; www.drkoop.com Diverticular Disease Source: Integrative Medicine Communications; www.drkoop.com Fatigue Source: Integrative Medicine Communications; www.drkoop.com Food Cravings Source: Integrative Medicine Communications; www.drkoop.com
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Gastritis Source: Healthnotes, Inc.; www.healthnotes.com Growth and Development Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Immune Function Source: Healthnotes, Inc.; www.healthnotes.com Impotence Source: Integrative Medicine Communications; www.drkoop.com Infection Source: Healthnotes, Inc.; www.healthnotes.com Irritable Bowel Syndrome Source: Integrative Medicine Communications; www.drkoop.com Irritable Bowel Syndrome Alternative names: Spastic Colon Source: Prima Communications, Inc.www.personalhealthzone.com Muscle Wasting Source: Integrative Medicine Communications; www.drkoop.com Obesity Source: Integrative Medicine Communications; www.drkoop.com Pancreatitis Source: Integrative Medicine Communications; www.drkoop.com Peptic Ulcer Source: Healthnotes, Inc.; www.healthnotes.com Peptic Ulcer Source: Integrative Medicine Communications; www.drkoop.com Peritonitis Source: Integrative Medicine Communications; www.drkoop.com Proctitis Source: Integrative Medicine Communications; www.drkoop.com Psychological Conditions and Disorders Source: Integrative Medicine Communications; www.drkoop.com
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Radiation Damage Source: Integrative Medicine Communications; www.drkoop.com Rectal Inflammation Source: Integrative Medicine Communications; www.drkoop.com Schizophrenia Source: Integrative Medicine Communications; www.drkoop.com Seizure Disorders Source: Integrative Medicine Communications; www.drkoop.com Sexual Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Shock Source: Integrative Medicine Communications; www.drkoop.com Stress Source: Integrative Medicine Communications; www.drkoop.com Ulcers Source: Prima Communications, Inc.www.personalhealthzone.com Wounds Source: Integrative Medicine Communications; www.drkoop.com •
Herbs and Supplements Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Arginine Source: Healthnotes, Inc.; www.healthnotes.com Carbamazepine Alternative names: Atretol, Carbatrol, Epitol, Tegretol, Tegretol XR Source: Prima Communications, Inc.www.personalhealthzone.com Chemotherapy Source: Healthnotes, Inc.; www.healthnotes.com Cyclophosphamide Source: Healthnotes, Inc.; www.healthnotes.com Docetaxel Source: Healthnotes, Inc.; www.healthnotes.com Fluorouracil Source: Healthnotes, Inc.; www.healthnotes.com
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GABA (Gamma-Amino Butyric Acid) Source: Healthnotes, Inc.; www.healthnotes.com Glutamic Acid Source: Healthnotes, Inc.; www.healthnotes.com Glutamine Source: Healthnotes, Inc.; www.healthnotes.com Glutamine Source: Integrative Medicine Communications; www.drkoop.com Glutamine Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html Glutathione Source: Healthnotes, Inc.; www.healthnotes.com Methotrexate Source: Healthnotes, Inc.; www.healthnotes.com Ornithine Alpha-Ketoglutarate Source: Healthnotes, Inc.; www.healthnotes.com Ornithine Alpha-Ketoglutarate Source: Prima Communications, Inc.www.personalhealthzone.com Paclitaxel Source: Healthnotes, Inc.; www.healthnotes.com Passiflora Alternative names: Passion Flower; Passiflora alata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Phenobarbital Alternative names: Bellatal, Solfoton Source: Prima Communications, Inc.www.personalhealthzone.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Primidone Alternative names: Mysoline Source: Prima Communications, Inc.www.personalhealthzone.com Proteolytic Enzymes Source: Prima Communications, Inc.www.personalhealthzone.com
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Tyrosine Source: Prima Communications, Inc.www.personalhealthzone.com Valproic Acid Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON GLUTAMINE Overview In this chapter, we will give you a bibliography on recent dissertations relating to glutamine. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “glutamine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glutamine, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Glutamine ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to glutamine. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Changes in the Amino Acid Content of Nerve Endings (Synaptosomes) Induced by Drugs That Alter the Metabolism of Gaba, Glutamate, Aspartate, and Glutamine by Geddes, James W; PhD from The University of Saskatchewan (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65349
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Effects of Dietary Glutamine on Sow and Litter Performance and Nursery Pig Performance and Intestine Growth by Kitt, Steven James; PhD from The University of Nebraska - Lincoln, 2003, 138 pages http://wwwlib.umi.com/dissertations/fullcit/3092564
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Effects of the Polyglutamine Neurodegenerative Protein Ataxin-3 on Transcriptional Regulation and the Ubiquitin-Proteasome Pathway by Li, Fusheng; PhD from University of Pennsylvania, 2003, 156 pages http://wwwlib.umi.com/dissertations/fullcit/3095910
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Enzymes of Glutamine Metabolism in Rat: Subcellular Localization of Glutaminases in Liver and Kidney Cortex and Characterization of Gamma-glutamyl Transferring
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Activities in Rat Kidney Cortex by Kalra, Jawahar; PhD from Memorial University of Newfoundland (Canada), 1976 http://wwwlib.umi.com/dissertations/fullcit/NK31417 •
Expression of Glutamine Synthetase in Early Life Stages of Rainbow Trout (Oncorhynchus mykiss) by Essex-Fraser, Phyllis Ann; MSC from University of Guelph (Canada), 2003, 99 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76067
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Glutamine and Asparagine Metabolism in Developing Endosperm of Corn by Misra, Santosh; PhD from McMaster University (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK65450
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Interaction between Neurons and Astrocytes in Glutamate and Glutamine Metabolism by Yu, Albert Cheung-Hoi; PhD from The University of Saskatchewan (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65328
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L-glutamine Modulation of Macromolecular Metabolism and Gene Expression during Differentiation and Sporulation in a Water Mould Achlya Klebsiana by Braithwaite, Cleantis Esewanu; PhD from The University of Manitoba (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37126
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Nuclear Localization of Polyglutamine Expressed in an Ectopic Context Correlates with Onset of Abnormalities in the Mouse by Jackson, Walker Scot; PhD from The University of Alabama at Birmingham, 2003, 127 pages http://wwwlib.umi.com/dissertations/fullcit/3101518
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On the Involvement of a Novel Proteolytic System in L-glutamine Control of Polyphosphate and Nucleic Acid Metabolism under Gyperthermic Conditions in Mammalian Cells Transformed by HA-RAS Oncogene, Sv40 Virus and 9,10-dimethyl1,2-benzanthracene by Deffie, Abdulai Mohamed; PhD from The University of Manitoba (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL37184
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. CLINICAL TRIALS AND GLUTAMINE Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning glutamine.
Recent Trials on Glutamine The following is a list of recent trials dedicated to glutamine.8 Further information on a trial is available at the Web site indicated. •
L-glutamine Therapy for Sickle Cell Anemia Condition(s): Anemia, Sickle Cell; Thalassemia Study Status: This study is currently recruiting patients. Sponsor(s): FDA Office of Orphan Products Development Purpose - Excerpt: This is a study to determine the efficacy of L-glutamine as therapy for sickle cell anemia and sickle O-thalassemia. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00029887
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions.
8
These are listed at www.ClinicalTrials.gov.
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The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “glutamine” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON GLUTAMINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “glutamine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glutamine, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Glutamine By performing a patent search focusing on glutamine, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on glutamine: •
Antibiotic peptides from bovine milk Inventor(s): Adermann; Knut (Hannover, DE), Forssmann; Wolf-Georg (Hannover, DE), Magert; Hans-Jurgen (Hannover, DE), Raida; Manfred (Heidelberg, DE), Zucht; HansDieter (Hannover, DE) Assignee(s): Haemopep Pharma Gmbh (hannover, De) Patent Number: 6,579,849 Date filed: September 24, 1998 Abstract: A peptide having the amino acid sequenceH.sub.2 N--X.sub.1 --R--X.sub.3 -X.sub.2 --COOH (formula I)whereinX.sub.1 is either zero orX.sub.1 and/or X.sub.2 are a residue representing at least five amino acid residues (symbolized in the one letter amino acid code), preferably naturally occurring amino acids,with the proviso thatX.sub.1 and/or X.sub.2 contain at least one basic amino acid residue immediately followed by a hydrophobic amino acid residue andX.sub.1 and/or X.sub.2 contain at least one glutamine residue. Excerpt(s): The present invention is concerned with peptides having the amino acid according to claim 1, fragments of the peptides obtainable by proteolytic cleavage, a medicament comprising a peptide of the invention, a process for the manufacturing of peptides of the invention, a method of treating by ad-ministering a peptide of the invention as well as methods of using the peptides of the invention. Antimicrobial peptides are small peptide compounds which are capable to decrease the incidence of disease and could serve as modulators of a naturally occurring bacterial flora (Ganz T. et al., 1992, Med. Microbiol. Immunol. 181, 99-105; Eisenhauer P. B. et al., 1992, Infect. Immun. 60, 3556-3565; Oulette A. J. et al., 1992, FEBS Lett. 304, 146-148; Jones D. E. and Bevins C. L., 1993, FEBS Lett. 315, 187-192; Selstedt M. E. et al. (1992) J. Cell. Biol. 118, 929-936). The fact that milk could influence micro-organisms is also well established (Wharton B. A. et al, 1994, Acta Paediatr. Jpn. 36, 579-584). Present factors thought to be responsible are lactoferrin (Bullen J. J. et al., 1972, Brit. J. Med. 1, 69-72; Baggiolini M. et al, 1970, J. Exp. Med. 13, 559-570), lysozyme (Fleming A., 1922, Proc. Roy. Soc., London, 93, 306-317, Jolles J. and Jolles P., 1968, Bull. Soc. Chim. Biol., Paris, 50, 2543-2551), lactoperoxidase (Cals M. M. et al., 1991, Eur. J. Biochem. 198, 733-739, Bullen J. J. et al., 1972, Brit. J. Med. 1, 69-72). Milk is a rich source of peptides mainly derived from proteolytic cleavage of proteins. Beyond a nutritive value several biological effects were described like immunomodulation, antithrombotic activities, opioid action or inhibition or mineral carriage (Meisel H. et al., 1989, Z. Ernahrungswiss. 28, 267-278; Fiat A. M. and Jolles P., 1989, Mol. Cell. Biochem. 87, 5-30; Fiat A. M. et al., 1993, J. Dairy. Sci. 76, 301310). Web site: http://www.delphion.com/details?pn=US06579849__
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Biological production of stable glutamine, poly-glutamine derivatives in transgenic organisms and their use for therapeutic purposes Inventor(s): Guerrant; Richard L. (Charlottesville, VA), Timko; Michael P. (Charlottesville, VA) Assignee(s): University of Virginia Patent Foundation (charlottesville, Va) Patent Number: 6,649,746 Date filed: May 2, 2000 Abstract: The invention provides a bioproduction of glutamine rich peptides. These peptides are used for rehydration and nutrition therapy in patients and for enhanced nutrition in animals. The peptides may be used as individual peptides or combined with other peptides in oligopeptides or proteins. Compositions of glutamine rich peptides and nucleic acid sequences for producing such peptides, as well as methods of production and use, are described. Excerpt(s): The present invention relates to stable glutamine derivatives and their use in rehydration and nutrition therapy and for enhanced nutrition in animals. More particularly the present invention is directed to the bioproduction of polypeptides comprising glutamine or glutamine rich regions and use of these polypeptides for rehydration and nutrition therapy and enhanced nutrition in animals. Glutamine is an amino acid which cotransports Na.sup.+ across the enterocyte brush border membrane. It is known to be the major bowel nutrient and energy source and has been used in intravenous solutions to improve nitrogen balance, inhibit protein breakdown, stimulate the growth of epithelial cells, and reduce intestinal villous atrophy. In addition, various researchers have shown that glutamine stimulates the absorption of sodium and chloride and have used glutamine in oral rehydration solutions to reduce cholera diarrhea. Viral enteritis is a leading cause of diarrhea in infants and toddlers less than two years old. Each year in the United States, about 22,000 infants are hospitalized for treatment of rotavirus-induced dehydration. In a majority of the cases, diarrheal disease morbidity and mortality is due to dehydration. The primary effect seen is the loss of fluid and electrolytes in diarrheal stools. An immediate effect in treatment of dehydration can be achieved by early oral administration of sugar (glucose) and electrolyte solution and continued feeding. However, conventional therapy by administration of oral rehydration formulations does not reduce stool volume or the duration of diarrhea. Thus, modifications of the oral rehydration therapy are needed to actually reduce stool volumes or speed the recovery of normal mucosal function, which in term will substantially enhance the acceptability and effectiveness of such therapy. The effects of organic compounds of salt and water absorption were first applied successfully to the treatment of patients with chloera and thereafter it was shown experimentally that the salt substrate cotransport was substantially intact in cholera patients and that oral therapy with sodium, chloride, potassium, biocarbonate and glucose in the same solution will restore and maintain normal blood volume and electrolyte concentrations, organic molecules such as D-hexoses, neutral amino acids, dipeptides and tripeptides of neutral amino acids, and water soluble vitamins can also enhance sodium absorption, following by water absorption in the small intestines. The present inventors have previously shown the efficacy of glutamine in intestinal sodium absorption. (Lima et al., Brazilian J. Med. Biol Res., 25; 637-640, (1992)). However, the greatest limitations to the oral use of glutamine is its instability and tendency to degrade in water and acid, conditions which are found in the stomach. Web site: http://www.delphion.com/details?pn=US06649746__
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Biologically active phytogenous proteoglycan and a method of making thereof Inventor(s): Chekanovskaya; Ludmila (ul, Tallinskaya, D 5, Korp. 2, Kv. 47, Moscow 12345, RU) Assignee(s): None Reported Patent Number: 6,274,146 Date filed: April 17, 2000 Abstract: A biologically active phytogenous proteoglycan not having hemagglutinating activity via water solution obtained by disintegration of divisible plant cells from young potato plants, Solanum tuberosum of the Family Solanaceae, fractionated and concentrated to obtain a dry substance with a molecular mass of 8.0.times.10.sup.5 2.5.times.10.sup.6 D and the mass percentages of the following elements: nitrogen 1.122.48%, carbon 39.93-44.42%, hydrogen 5.15-7.21%; the remaining is an ash component, which includes a polysaccharide chain consisting of residues of neutral sugars in the amount of 34.0-85.3% and in the following mass percentages: glucose 26.4-33.1%, galacturonic acid 19.0-25.1%, arabinose 1.7-4.4%, uronic acids 12.0-18.0%, rhamnose 1.210.0%, xylose 0.1-3.0%, mannose 0.1-5.0%, galactose 2.5-27.0%; and up to 15 ng of pro that consists of amino acids residues in the following quantities based on ng per 0.1 mg of proteoglycan: asparagine 126.0-146.0 ng, serine 139.0-159.0 ng, glutamine 263.0-283.0 ng, glycine 117.0-131.0 ng, alanine 80.0-100.0 ng, valine 76.0-96.0 ng, leucine 85.0-105.0 ng, lysine 62.0-85.0 ng, arginine 42.0-62.0 ng; and trace amounts of cysteine, isoleucine, histidine, phenylalanine, tyrosine, and threonine. Excerpt(s): The invention refers to biologically active substances and, in particular, to phytogenous proteoglycans applied in medicine, pharmacology, veterinary medicine, and biology as a component of medicinal products. Bioactive polysaccharide.gamma.PL (gamma-plant) is also known, which is extracted from plant cells, for example from corn, potato, marine fungus, etc. With the molecular mass equal to 2.times.10.sup.6.+.9.times.10.sup.5 D and element composition (mass %) as follows: nitrogen 1.7-1.98; carbon 40.12-40.39; hydrogen 5.81-6.07; the remainder is the ash component which includes the polysaccharide chain consisting of (mass %) neutral carbohydrate residues (35.0-41.0), glucose (27.0-33.0), galacturonic acid (19.0-25.0), arabinose (1.7-2.3), uronic acids (12.0-18.0) and protein (no less than 0.5) that consists of amino acids residues in the following quantities (per 0.1 g of.crclbar.-pl): asparagin 126.0-146.0, serine 139.0-159.0, glutamine 263.0-283.0, glycine 117.0-131.0, alanine 80.0-100.0, valine 76.0-96.0, leucine 85.0-105.0, lysine 65.0-85.0, arginine 42.0-62.0; in trace quantities are: cystein, isoleucine, histidine, phenylalanine, tyrosine, threonine. As an anti-infective agent gPL was studied during treatment of viral and bacterial infections in laboratory and agricultural animals. With experimental infection of mice by viruses of simple herpes such as 1 and 2 types on the model of herpetic meningocephalitis at application of a dose 10LD.sub.50 gPL protective effect reached 60%. Comparatively narrow range of anti-infective activity as well as an occurrences of local inflammatory reactions while subcutaneous injections are gPL applications shortcomings. It is therefore an object of the present invention to eliminate the shortcomings mentioned above by creation of a new substance having a broad spectrum of anti-infectious activities and free from side effects. Web site: http://www.delphion.com/details?pn=US06274146__
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Compositions of matter containing L-glutamine and pyridoxal-alpha-ketoglutarate Inventor(s): Jaffe; Russell (10430 Hunter View, Vienna, VA 22181) Assignee(s): None Reported Patent Number: 6,545,044 Date filed: May 30, 2001 Abstract: Compositions having synergistic effects which make it possible to obtain full beneficial effects of L-glutamine while avoiding the toxic effects that may accompany administration of L-glutamine. This benefit is attained by administration of L-glutamine in conjunction with pyridoxal-alpha-ketoglutarate (PAK). Compositions containing PAK:L-glutamine at a ratio (w/w) of from 1:1 to 1:10 are effective for providing beneficial effects of L-glutamine at nontoxic levels. Excerpt(s): This invention relates to use of beneficial synergistic administration of Lglutamine in conjunction with pyridoxal-alpha-ketoglutarate (PAK) to stimulate repair of tissues dependent on high turnover of cells. The use of L-glutamine, a basic amino acid, to provide an energy source for cells having a rapid turnover, such as cells of the mucosa of the intestine, has been known. Patients in need of significant stimulation of growth and repair of intestinal mucosa include those who have undergone surgical resection of the intestine and those suffering from chronic diseases as enteropathy (atrophy of the intestine) and persistent inflammatory bowel syndrome (IBS). Furthermore, certain infectious diseases and treatment modalities such as administration of antibodies can cause severe damage to the gastrointestinal mucosa. However, large amounts of L-glutamine are needed to achieve clinical results. Concerns have been raised about the high dosages. The build-up of L-glutamine (derived from energy-producing deamination of L-glutamine), which can act as an exitoneurotoxin. The difficulty resulting from this effect has greatly decreased the use of L-glutamine to provide benefit to those needing tissue repair. Hence, there is need for treatment modalities that will provide the benefits of L-glutamine which are not accompanied by the metabolic imbalance and potential toxic side effects seen under prior regimens. While the compositions of the invention may be used for stimulation of growth and repair of other cells which usually undergo rapid replacement in the body, the cells of the intestinal mucosa offer a reliable model that is conventionally used to study stimulation of growth and repair of cells. The instant invention provides compositions having synergistic effects which make it possible to obtain full beneficial effects available using L-glutamine whilst avoiding the toxic effects that may accompany administration of L-glutamine. This benefit is attained by administration of L-glutamine in conjunction with pyridoxal-alpha-ketoglutarate (PAK). Compositions containing PAK:L-glutamine at a ratio (w/w) of from 1:1 to 1:10 are effective for providing beneficial effects of L-glutamine at nontoxic levels. Web site: http://www.delphion.com/details?pn=US06545044__
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Cyclic lipopeptide from Cryptosporiopsis quercina possessing antifungal activity Inventor(s): Strobel; Gary A. (Bozeman, MT) Assignee(s): Hmv Corporation (alpine, Ut) Patent Number: 6,613,738 Date filed: May 30, 2001
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Abstract: A unique lipopeptide antimycotic, termed Cryptocandin, is described from Cryptosporiopsis cf quercina, an endophytic fungus. Cryptocandin with a molecular mass of 1079 contains equimolar amounts of 1,2-dihydroxy-homotyrosine, 4-hydroxy proline, threonine, glutamine, 3-hydroxy-4-hydroxy methyl proline, 4,5 dihydroxy ornithine, and palmitic acid. Cryptocandin is chemically related to well-known antimycotics, the echinocandins, and pneumocandins which are produced by such fungi as Zalerion arboricola, Pezicula spp., and Aspergillus spp. Cryptocandin has minimum inhibitory concentration values less than 0.03.mu.g ml.sup.-1 against isolates of Candida albicans, Trichophyton mentagrophytes and Trichophyton rubrum. Cryptocandin is also active against a number of plant pathogenic fungi including Sclerotinia sclerotiorum and Botrytis cinerea. Excerpt(s): The present invention is related to the isolation of an antimycotic compound. The present invention is also related to an antimycotic composition comprising the compound, and a method for controlling or treating fungal infection, particularly in humans and plants. Human and plant infections caused by pathogenic fungi are a continuing and serious problem. Thus, the discovery and characterization of novel, effective antimycotics is especially important. In the case of humans, the increase in fungal infections has resulted, in part, from the frequent use of antibacterial compounds, which enhances opportunities for fungal infections. Furthermore, there is a worldwide increase in the number of immunocompromised patients who are susceptible to fungal infections. This patient population has resulted from the AIDS epidemic, chemotherapy of cancer patients, and the profusion of organ transplant patients (Miller et al., 1998). Cryptosporiopsis cf. quercina is the imperfect stage of Pezicula cinnamomea, a fungus commonly associated with hardwood species in Europe (Sutton, 1980). This fungus and related species occur as endophytes and plant pathogens in many parts of the world (Sutton, 1980). Certain Pezicula spp. and Zalerion arboricola produce one or more members of a family of antimycotics, (lipopeptides) known as the pneumocandins. Related lipopeptides, the echinocandins, are also produced by Aspergillus species. Web site: http://www.delphion.com/details?pn=US06613738__ •
Dietary supplement for increasing energy, strength, and immune function Inventor(s): Tuttle; B. David (1830 Stoner Ave., Los Angeles, CA 90025) Assignee(s): None Reported Patent Number: 6,465,018 Date filed: September 26, 2000 Abstract: A dietary supplement is provided that comprises creatine combined with ginseng and astragalus and, optionally, glutamine. The dietary supplement enhances the general energy boost and muscular strength increase achieved from the consumption of creatine alone, while also increasing immune function. Excerpt(s): The present invention relates generally to dietary supplements, and, more particularly, to a blend of creatine, ginseng, and astragalus, and, optionally, glutamine for increasing energy, strength, and immune function. As we age, our bodies undergo a variety of changes. We often lose strength and energy due to declines in hormone levels and a more sedentary lifestyle. These changes can frequently interact with each other to produce compounding effects. For example, the loss in muscle strength increases the likelihood of falls and broken bones, which can lead to further declines in physical activity and strength. While some of these declines in strength and energy levels are
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inevitable, they can also result from nutritional deficiencies and changes in lifestyle patterns. This is partly responsible for the greater utilization of medical resources by senior citizens and consequent impacts on Medicare expenditures. Creatine is a nutrient that increases protein synthesis and intra-cellular water levels within the muscle fibers, resulting in greater strength and muscle mass. This boosts daily caloric expenditure, which will lower body-fat stores if food intake is unchanged. A discussion of the benefits may be found in a book by Ray Sahelian and Dave Tuttle, entitled Creatine: Nature's Muscle Builder, Avery Publishing Group (1997). Web site: http://www.delphion.com/details?pn=US06465018__ •
Food-based delivery of HGH-stimulating and other nutritional supplements Inventor(s): Marshall; Edward (10932 Savona Rd., Los Angeles, CA 90077) Assignee(s): None Reported Patent Number: 6,461,634 Date filed: August 17, 2000 Abstract: A food, or ready-to-drink beverage, delivery system for increasing the production and release of human growth hormone (HGH) for anti-aging effects and/or to improve a condition of HGH deficiency. A food bar, powder, other food forms, or ready-to-drink beverage that contains the full range and optimal dosages of vitamins, minerals, non-prescription hormonal and herbal supplements most desired by individuals who regularly take such supplements from numerous bottles or other packages. HGH stimulation and the above-described supplementation may be delivered for oral ingestion separately or together in the same aliquot, said aliquot providing a pleasant-tasting and convenient snack or mini-meal in addition to the specific HGH stimulation and supplementation. L-glutamine, glycine and melatonin are sufficient to boost HGH up to age 60, and it is preferred to add L-arginine and L-lysine for individuals of age 60 and older. The single food or beverage aliquot makes unnecessary the inconvenient ingestion of numerous pills from numerous bottles, or ill-tasting powders that must be mixed with water. Calories are kept under about 300, and carbohydrate is kept generally below about 5 grams per aliquot in order to permit the stimulation of HGH when the stimulating ingredients are consumed in the form of food or nutritional ready-to-drink beverage. Ingredients are included as needed for optimal flavor and texture choices, and to prevent spoilage. Excerpt(s): The present invention relates to a food-based delivery system for providing (a) the required nutritional supplements for stimulating production and release of human growth hormone (HGH) and/or (b) a full range and desired dosages of vitamins and minerals consumed each day by serious takers of such supplements. In more detail, the present invention relates to combinations of amino acids, vitamins, and other nutrients formulated into a convenient and good-tasting food such as a food bar or ready-to-drink beverage that, when ingested orally, stimulates HGH production and/or release for the purpose of producing anti-aging effects. The same food is formulated to provide the full range of the most commonly desired vitamins and minerals consumed by adults who are serious consumers of vitamin and mineral supplements or the vitamins and minerals can be formulated separately for ingestion without the HGHstimulating amino acids and other nutrients. Either way, the food-based delivery system of the present invention provides a full complement of the vitamins, minerals, and other nutritional supplements in adequate quantity to satisfy most serious consumers of such supplements in a pleasant-tasting form. With regard to the prior art, it is known to those
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skilled in the art and to many of the public in general, that HGH levels fall with age starting at about age 35, so that HGH levels are reduced by about two-thirds by the age of 60. It is know that when the HGH levels are restored to more youthful levels, by a schedule of either injections of HGH, or the oral consumption of certain combinations of amino acids, over the ensuing 20 to 180 days, anti-aging effects occur, including: boosting of the immune system, restoration of more youthful vigor and libido, increase of the percentage of lean muscle mass, reduction of the percentage of body fat, increase in the thickness of skin with more youthful texture, increased skin turgor and a decrease of brown "aging" spots. The beneficial anti-aging effects of increased levels of growth hormone in humans are well documented. See, for instance, R. Klatz, et al., Grow Young with HGH, New York, HarperCollins Publishers, 1997; see also D. Rudman, et al., Effects of Human Growth Hormone in Men Over 60 Years Old; New England Journal of Medicine, 1990; vol 323; 1:1. In the book by Klatz there are numerous references to published and unpublished studies showing the efficacy of orally ingested amino acids in elevating HGH levels and HGH has long been given by injection. The disadvantages of these prior art methods, however, are several: HGH injections are painful and inconvenient, and the cost usually exceeds $10,000 per year. There can be side effects if the injected dosage is too high for the individual. Injections require careful monitoring of blood laboratory tests and careful physician follow-up. If the person is to take the available pill form of HGH-stimulating amino acids, he/she must take eight to sixteen different pills from four to five different bottles one to four times a day. Some of the pills are quite large, and if one is to take all four of the recommended amino acids in correct dosage, one would have to take is pills from as many as four different bottles at each dosage time, for a total of about 16 pills per dose. Further inconvenience is caused by the fact that the pills of the different bottles run out at different intervals, requiring numerous trips to health food stores. In many locales, some of the ingredients are not available for sale in any store. Typical schedules require taking the pills 6 out of 7 days, with breaks of 2 to 6 weeks every 3 to 6 months, and missing any of the recommended dosages or pills can lessen the desired effects. Web site: http://www.delphion.com/details?pn=US06461634__ •
Functionalized poly(propylene fumarate) and poly(propylene fumarate-co-ethylene glycol) Inventor(s): Jo; Seongbong (Houston, TX), Mikos; Antonios G. (Houston, TX) Assignee(s): Wm. Marsh Rice University (houston, Tx) Patent Number: 6,306,821 Date filed: April 14, 2000 Abstract: Poly(ethylene glycol) (PEG), a highly biocompatible hydrophilic polyether, is tethered to poly(propylene fumarate) (PPF), a biodegradable polyester. To avoid change in molecular weight distribution of PPF, end hydroxyl groups of PPF are reacted with bis-carboxymethyl PEG after being treated with thionyl chloride. New end carboxyl groups of the PEG-tethered PPF are further reacted with N-hydroxysuccinimide (NHS) in the presence of dicyclohexylcarbodiimide (DCC) to couple bioactive molecules. Glutamine and glycine-arginine-glycine-aspartic acid (GRGD) are attached to the PEGtethered PPF in 50 mM phosphate buffer of pH of 7.4. The method is valuable for the preparation of a triblock copolymer with PEG end blocks and the coupling of biologically active molecules.
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Excerpt(s): This invention relates to a compound for replacing or reconstructing rigid or semi-rigid living tissue. More particularly, the present invention relates to a method for tethering PEG to PPF ends and for modifying the remaining carboxyl end groups of PEG-tethered PPF so they can be further modified with peptides, so as to form poly(propylene fumarate-co-peptide). In the field of tissue engineering, degradable biomaterials usually serve as a scaffold to provide mechanical support and a matrix for the ingrowth of new tissue. As new tissue forms on the scaffold, the biomaterial degrades until it is entirely dissolved. The degradation products are eliminated through the body's natural pathways, such as metabolic processes. One example of the use of such biomaterials is as a temporary bone replacement. It is often desired to replace or reconstruct all or a portion of a living bone, such as when a bone has been broken or has been resected as a result of a bone tumor. In these instances, the missing bone can be replaced with a mechanical device, such as a pin, plate or the like, or it can be replaced with an implant that is designed to more closely resemble the original bone itself. Often these implants comprise biodegradable polymeric compounds or parts made from such compounds. It is contemplated that bone tissue will grow back into the pores of the implant and will gradually replace the entire implant as the implant itself is gradually degraded in the in vivo environment. For obvious reasons then, such implants should be biocompatible and non-toxic. Web site: http://www.delphion.com/details?pn=US06306821__ •
Herbal formulation for rebuilding intestinal bacteria Inventor(s): Terry; Travis L. (Clearwater, FL), Watson; Brenda F. (Tarpon Springs, FL), Watson; Tommy Stanley (Tarpon Springs, FL) Assignee(s): Renew Life, Inc. (clearwater, Fl) Patent Number: 6,426,099 Date filed: December 1, 1998 Abstract: An herbal formulation comprises betaine HCl, plant enzymes, papain, probiotic micro flora, fruitooligosaccharides, l-glutamine, quercitin, butyric acid, borage seed, flax seed, lecithin, gamma oryzanol, bromelain, pepsin, and N-acetylglucosamine. Excerpt(s): This invention relates generally to an herbal food supplement and formulation for rebuilding intestinal bacteria. More particularly, the invention is directed to a probiotic formulation containing plant enzymes and micro flora effective for reestablishing healthy intestinal bacteria and rebuilding intestinal mucosa. Leaky gut is a condition in which the mucosa of the intestinal tract is compromised, thereby allowing toxins and food particles to penetrate the lining of the intestinal tract and enter the body's blood stream. The body itself may naturally attempt to counteract this phenomenon, usually with several negative side effects. Firstly, the body may attempt to produce antibodies to combat the toxins. This will result in the body developing allergies to the foods which have caused the breakdown of the intestinal tract lining. Furthermore, the liver may increase its production of detoxifying enzymes. The activation of some of these enzymes may release harmful free radicals as a byproduct. These oxidizing free radicals may, in turn, damage the liver and other tissues, resulting in a weakened immune system. Symptoms of leaky gut may include irritable bowel disease, chronic fatigue, food allergies, and arthritis. Web site: http://www.delphion.com/details?pn=US06426099__
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Keto acid salts and amine derivatives, and their use for preparing medicines Inventor(s): Biosa; Serge (Mantes la Jolie, FR), Bouyssou; Thierry (Beynes, FR), Jeanpetit; Christian (Bougival, FR), Settembre; Pierre-Andre (Houilles, FR) Assignee(s): Chiesi S.a. (courbevoie, Fr) Patent Number: 6,429,229 Date filed: November 13, 2000 Abstract: The invention concerns the use of compounds of general formula (I): (X).sub.n1,Y,(Z).sub.n2 wherein n1 and n2 represent 0 or 1; X represents a natural amino acid, in particular an amino acid selected among ornithine, arginine, lysine, histidine or glutamine; Y represents a keto acid of formula (II): R--CO--COOH wherein R represents --CH.sub.3, --CH.sub.2 --CH.sub.3, --CH(CH.sub.3).sub.2, --CH(CH.sub.3)--CH.sub.2 -CH.sub.3, --CH.sub.2 --CH(CH.sub.3).sub.2, --CH.sub.2).sub.2 --COOH, -CH.sub.2).sub.3 --COOH; Z represents: a natural amino acid selected in particular among ornithine, arginine, lysine, histidine or glutamine; or a polyamine selected in particular among cadaverine, putrescine, spermidine, spermine or agmatine. Said compounds are useful for preparing a medicine for treating human or animal pathologies wherein are involved silent neurons, such as pathologies of the digestive tract, the bladder and the biliary ducts. Excerpt(s): The present invention has for its objects salts of keto acids and of amine derivatives, as well as their use for the preparation of pharmaceutical compositions for the treatment of pathologies in which are involved silent neurons. The nociceptive message results from the intense activation of the free terminals (nociceptors) of the C and A.delta. fibers which under physiological conditions take part in the regulation of the function of the organs. These fibers are contained in the cutaneous, muscular and articular tissues as well as in the walls of the viscera. In the digestive tract as well as in the bladder and the biliary ducts, this nerve structure cohabits with a population of silent neurons (Mayer, E. A.; Gebhart, G. F.; Gastroenterology, 1994, 107, 271-293) whose expression appears only in the presence of an inflammatory or nervous lesion. Web site: http://www.delphion.com/details?pn=US06429229__
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Ketosis-treating agent Inventor(s): Kobayashi; Hisamine (Kanagawa, JP) Assignee(s): Ajinomoto Co., Inc. (tokyo, Jp) Patent Number: 6,620,967 Date filed: October 17, 2000 Abstract: A ketosis-treating agent comprising, as an active ingredient, at least one amino acid selected from valine, isoleucine, serine, glutamine and glutamic acid, or a peptide or protein comprising at least one amino acid selected from valine, isoleucine, serine, glutamine and glutamic acid; a method for treating or preventing ketosis, comprising administering to a human or animal an effective amount of the above agent; and a method for treating or preventing symptoms relating to ketone bodies, comprising administering to a human or animal an effective amount of the above agent. Excerpt(s): The present invention relates to a ketosis-treating agent. Particularly, it relates to a ketosis-treating agent which shows little influence on glucose metabolism and/or has a long duration of its effect. Mobilization of free fatty acids from fatty tissue
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increases at diabetes, starvation, physical exercise, external injury, surgical operation, attack of fever, or the like, so that fatty acid oxidation in the liver is accelerated because of decrease of utilization of sugars, deficiency of insulin, stress, and the like. As a result, formation of ketone bodies, which is the general term for acetoacetic acid, 3hydroxybutyric acid and acetone, increases. When the formation of ketone bodies exceeds the capacity of treating it, the ketone bodies are accumulated in blood to cause ketonemia. Conditions where the concentration of ketone bodies is high in urine are called ketonuria, and both of them are called generally ketosis. Since acetoacetic acid and 3-hydroxybutyric acid are strong acids of a medium level, in the case where accumulation of ketone bodies exceeds the buffering capacity of a living body, metabolic acidosis is caused and the living body falls into a fatal state called ketoacidosis. For example, excessive formation of ketone bodies for a long period, of time such as diabetes causes ketoacidosis to finally result in death. Generally, in order to prevent or treat ketosis, insulin or a sugar, such as glucose or the like, is administered. However, as discussed above, glucose metabolism is disordered in many cases of falling into ketosis so that there is a problem that a blood glucose value largely varies by such administration of insulin or a sugar. Web site: http://www.delphion.com/details?pn=US06620967__ •
Localization and characterization of the Wilms' tumor gene Inventor(s): Breuning; Wendy (Montreal, CA), Buckler; Alan J. (Brookline, MA), Call; Katherine M. (Malden, MA), Darveau; Andre (St. Foy, CA), Glaser; Thomas M. (Cambridge, MA), Haber; Daniel A. (Cambridge, MA), Housman; David E. (Newton, MA), Ito; Caryn Y. (Chapel Hill, NC), Pelletier; Jerry (St. Leonard, CA), Rose; Elise A. (Oakland, CA) Assignee(s): Massachusetts Institute of Technology (cambridge, Ma) Patent Number: 6,316,599 Date filed: March 9, 1998 Abstract: The Wilms' tumor gene associated with 11p3 locus on the human chromosome, as well as a method of analyzing cells for the gene is described and characterized. The gene encodes a transcription unit approximately 50 kb in size and a mRNA of approximately 3 kb, which is expressed in predominantly in kidney and gonadal tissue. The gene is alternative spliced producing four very similar mRNA transcripts. The polypeptides encoded by the Wilms' tumor DNA includes four "zinc fingers" and a region rich in proline and glutamine, suggesting that the polypeptide has a role in transcription regulation. Excerpt(s): Work described herein was funded by the National Institutes of Health, the Medical Research Council of Canada and the National Cancer Institute. Wilms' tumor (WT) is an embryonal malignancy of the kidney which affects approximately 1 in 10,000 infants and young children. Matsunaga, Human Genetics, 57:231-246 (1981). The molecular basis of Wilms' tumor is not well understood. The majority of WTs are sporadic tumors (>95%). A small set of WTs occur in a hereditary setting as familial cases or as part of cogential disorders such as the WAGR syndrome. Wilms' tumor (W) cases (approximately 2%) can occur in association with aniridia (A), a defect in the development of the iris, as well as genitourinary (G) abnormalities and mental retardation (R). Miller et al., New Engl. J. Med., 270:922-927 (1964). These disorders form the WAGR syndrome, and can be attributed to a constitutional deletion of DNA in band 11p13 on human chromosome 11 in a group of genes known as the WAGR complex.
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Riccardi, et al., Pediatrics, 61:604-610 (1978); Francke, et al., Cytogenet. Cell Genet., 24: 185-192 (1979). In these cases, bilateral Wilms' tumors are frequently observed, as are dysplastic changes in surrounding renal tissue (nephroblastomatosis) which are though to precede malignant transformation (i.e., precancerous conditions). Bove and McAdams, Perspectives on Pediatric Pathol., 3:185-223 (1976). As a recessive oncogene or anti-oncogene, the Wilms' tumor locus is thought to curtail the growth of undifferentiated nephrotic cells. The genetics of WT generally conform to the two-hit mutational model of carcinogenesis used to describe the retinoblastoma locus on chromosome 13q. According to this concept, the rate-limiting events in tumor formation are two mutations. Sporadic tumors develop following two independent events, while familial cases involve transmission of one altered gene in the germline and a somatic mutation in the second gene. Hereditary cases display both a high penetrance and an increased incidence of bilateral cancers, attesting to the frequency of the somatic second event. Web site: http://www.delphion.com/details?pn=US06316599__ •
Material for passage through the blood-brain barrier Inventor(s): Naito; Albert T. (2776 Cibola, Costa Mesa, CA 92626) Assignee(s): None Reported Patent Number: 6,294,520 Date filed: March 27, 1989 Abstract: A material which has the ability to effect it's passage, at least in part, and the ability to transport other materials through the blood-brain barrier which includes any one or more pure sugars or pure amino sugars from the group consisting of meso ethritol, zylitol, D(+) galactose, D(+) lactose, D(+) xylose, dulcitol, myo-insoitol, L(-) fructose, D(-) mannitol, sorbitol, D(+) glucose, D(+) arabinose, D(-) arabinose, celloboise, D(+) maltose, D(+) raffinose, L(+)rhamnose, D(+) melibiose, D(-) ribose, adonitol, D(+) arabitol, L(-) arabitol, D(+) fucose, L(-) fucose, D(-) lyxose, L(+) lyxose, L(-) lyxose, D(+) glucosamine, D mannosamine, and D galactosamine; and any one or more amino acids from the group consisting of arginine, asparagine, aspartic acid, cysteine, glutamic acid, glycine, histidine, leucine, methionine, phenylalanine, proline, serine, threonine, glutamine, lysine, tryptophan, tyrosine, valine, and taurine. For use in the research or treatment of a subject that material is combined with one or more of the substances beta carotene, xanthophyll, lecithin, calcium, somatostatin, vasopressin, endorphin, enkephalin, acetyl-L-carnitine, GABA, dynorphin, L-tryptophan, choline, thiamine, pyridoxine, niacin, L-arginine, hydroxyproline, NGF, methionine, cystine, potassium, phosphorus, chlorine, sodium, vitamins A, B, C, D and E, and selenium. Excerpt(s): This invention relates to materials and methods for passing, and transporting other substances, through the blood-brain barrier. If one accepts the premise that most physiological functions are controlled by the brain and the medium of that control is electrical signalling as an incident to chemical activity in the brain, then it seems logical to conclude that an absence in the brain of the chemicals required for that activity can result in signal failure and consequent physiological disfunction. It is possible also to conclude that a genetic trait which interferes with such chemical activity can result in signal failure and disfunction. It is also possible to conclude that the presence of a given substance in the brain may interfere chemically with the proper generation of control signals. Such considerations, the search for an understanding of the mechanism of drug dependence, drunkenness, Alzheimer's disease, schizophrenia and other disorders,
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some associated with the brain and others apparently not, have lead many researchers to look for a relation between such disorders and availability of chemicals in the brain. The medical literature includes descriptions that comparison of brain tissue of persons who succumbed to a given disease with that of persons who died of unrelated causes suggest a relation between a given chemical and the disease. Thus lack of lithium has been mentioned in connection with schizophrenia and lack of neuropeptides has been mentioned in connection with Alzheimer's disease. Web site: http://www.delphion.com/details?pn=US06294520__ •
Measurement of gastric emptying using stable isotopes Inventor(s): Mehta; Devendra Indulal (Cherry Hill, NJ) Assignee(s): The Nemours Foundation (wilmington, De) Patent Number: 6,432,382 Date filed: October 20, 2000 Abstract: The invention provides a diagnostic test for gastrointestinal disorders by providing a safe, convenient, reliable method for measuring gastric emptying. In this test, a tracer amount of.sup.13 C-glutamine or.sup.13 C-glutamic acid is added to a liquid meal, or.sup.13 C-glutamic acid added to a solid meal. After digestion in the stomach, the meal is emptied into the small bowel, where the labeled.sup.13 C-tracer is immediately taken up and metabolized by the cells lining the small bowel. The released.sup.13 CO.sub.2 is detected in the breath. The measurement of rise in the level of.sup.13 CO.sub.2 as a function of time is correlated to the rate of gastric emptying. Excerpt(s): This invention relates to a diagnostic test for gastrointestinal disorders in humans to determine whether a meal being digested in the stomach is emptied into the small intestine at a normal rate. In pathologic states, the rate can be abnormally accelerated or diminished. During gastric emptying, ingested food is mixed with gastric juices. After appropriate dilution, the food is then emptied into the small bowel for further digestion and absorption. This is a complex, carefully regulated system involving hormones, receptors, nerves, and muscles of the stomach, and a consistent rate and concentration of the final content is emptied into the small bowel. Many factors, such as the fat composition or type of protein in the food, affect this carefully regulated emptying of liquids. The emptying mechanism can be affected by many disorders and lead to either delayed emptying or rapid emptying (dumping). Delayed emptying can lead to symptoms of nausea, vomiting, abdominal pain, and poor growth. Dumping can lead to retching, abdominal pain, flatulence, diarrhea, poor weight gain, and dangerously low blood glucose levels. To establish a diagnosis and enable further medical management of a patient, the rate of gastric emptying often must be measured. There are various therapies for delayed or rapid emptying, but their efficacy is often unclear. The rates for emptying for solids and liquids differ. In infants and small children, the rate of liquid emptying is particularly important. Web site: http://www.delphion.com/details?pn=US06432382__
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Method for improving a human's perception of his emotional state Inventor(s): Nissen; Steven L. (Ames, IA) Assignee(s): Iowa State University Research Foundation, Inc. (ames, Ia) Patent Number: 6,291,525 Date filed: September 8, 1999 Abstract: The present invention provides a method for improving a human's perception of his emotional state. The method comprises administering.beta.-hydroxy-.beta.methylbutyric acid to the human in an amount sufficient to improve his perception of his emotional state. The method can further comprise co-administering arginine and glutamine and/or engaging the human in non-resistance training. Excerpt(s): The present invention relates to a method for improving a human's perception of his emotional state by administering.beta.-hydroxy-.beta.-methylbutyric acid (HMB) to a human. Mood disorders are the most common serious psychiatric problem facing people today. It has been estimated that during any one-year period, 17.6 million American adults or 10% of the population suffer from a mood disorder, such as a depressive illness. A depressive disorder is a "whole-body" illness, which involves the body, mood, and thoughts. It affects the way one eats and sleeps, the way one feels about oneself, and the way one views the world. Depressive disorders come in different forms, ranging from major depression to a less severe form of depression called dysthymia. Dysthymia involves long-term, chronic symptoms that do not disable, but keep one from operating at full potential or from feeling good. Common symptoms of depressive illness include, among other symptoms: (1) persistent sad, anxious, or "empty" mood; (2) feelings of hopelessness and pessimism; (3) feelings of guilt, worthlessness, and helplessness; (4) loss of interest or pleasure in hobbies that were once enjoyed; (5) decreased energy and increased fatigue; 6) restlessness and irritability; and (7) difficulty in concentrating, remembering, and making decisions. The cost of depressive disorders, in terms of human suffering, cannot be underestimated. Depressive illnesses interfere with normal functioning and cause significant pain and suffering, not only to those who have the disorder, but also to those who care about them. Furthermore, the economic cost of depressive illness has been estimated to be $3044 billion a year, with an estimated 200,000,000 lost work days annually and a loss of productivity, due to the nature of depressive symptoms. Possibly the saddest fact about depressive disorders is that much of the suffering is unnecessary. Most people with a depressive illness do not seek treatment, due to the stigma attached with depressive disorders or a lack of access to the health care system. Web site: http://www.delphion.com/details?pn=US06291525__
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Method for the modification of protein structure in finish shaped feed pellets, balls or the like in order to achieve shape stability, and feed mass made in accordance with the method Inventor(s): Hoff; Kjell Arne (Sandnes, NO), Thorsen; Fred Hirth (Hundv.ang.g, NO) Assignee(s): Nutreco Aquaculture Research Centre A/s (no) Patent Number: 6,399,117 Date filed: October 6, 2000
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Abstract: A method for producing feed for forming into pellets, the pellets produced by the method to be used to feed carnivorous animals. The addition of the enzyme transglutaminase to a feed mass specifically intended for carnivorous fish will catalyze a reaction between the amino acids glutamine and lysine which form part of the protein chains and the raw material of the proteins of the feed, such that a covalent chemical bond is formed between them, which results in shape permanence in the formed, dried, finished pellets, such that the finished pellets do not lose their shape before time of use. Excerpt(s): The present invention relates to a method for the modification of protein structure in finish shaped feed pellets, balls or the like, among other reasons in order to contribute to strengthening the permanence of the pellet shape in granular feeds of this sort. The invention also relates to feedstuff manufactured according to this method for the formation of a shape-permanent feed in pellet form. Many types of animals in breeding, e.g. salmon and trout, are carnivorous (meat-eating). Their natural food consists of insects (for salmon and trout in the freshwater phase), fish and crustaceans. For other carnivorous farmed animals, such as mink and foxes, the feed may also contain the mammalian flesh, for example fresh slaughterhouse waste. Insects and crustaceans have an exoskeleton which i.e. consists chitin. Chitin is a linear polysaccharide of N-acetyl-D-glucosamine linked by.beta.1.fwdarw.4 bonds. Other structural carbohydrates such as cellulose (.beta.[1.fwdarw.4] D-glycose) and alginate (D-mannuronic acid) are not found in these prey animals, nor do they contain starch (.alpha. [1.fwdarw.4] D-glycose) as energy stores. Nevertheless, salmon, trout and other carnivorous fish and animals have enzymes (for example, amylase) that are capable of breaking down starch in the gut and making it digestible, but they may be less efficient in this respect than herbivorous (plant-eating) fish and animals. In feeds intended for carnivorous fish it is usual to add between 8% and 25% carbohydrates, for example in the form of wheat or maize, as a binding agent. After pressing, but especially after extrusion, the starch in these carbohydrates will form a matrix or base mass which gives the pellets mechanical strength and shape permanents so that the shape of the pellets can be maintained after drying, further processing, storage and transport. Web site: http://www.delphion.com/details?pn=US06399117__ •
Method of treating asthma using soluble IL-9 receptor variants Inventor(s): Grasso; Luigi (Philadelphia, PA), Holroyd; Kenneth J. (Collegeville, PA), Levitt; Roy Clifford (Ambler, PA), Nicolaides; Nicholas C. (Boothwyn, PA) Assignee(s): Genaera Corporation (plymouth Meeting, Pa) Patent Number: 6,602,850 Date filed: June 16, 2000 Abstract: This invention relates to the diagnosis, treatment and methods for discovery of new therapeutics for atopic asthma and related disorders based on variants of Asthma Associated Factor 2. One embodiment of the invention is a variant of AAF2 wherein codon 173 is deleted resulting in the loss of glutamine 173 from the mature protein precursor. This single amino acid deletion results in a non-functional AAF2 protein and therefore the presence of this phenotype should be associated with less evidence of atopic asthma. Correspondingly, the lack of susceptibility to an asthmatic, atopic phenotype is characterized by the loss of glutamine at codon 173. The invention includes isolated DNA molecules which are variants of the wild type sequence as well as the proteins encoded by such DNA and the use of such DNA molecules and expressed protein in the diagnosis and treatment of atopic asthma.
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Excerpt(s): This invention describes biologic variability in the IL-9 receptor (Asthma Associated Factor 2) (SEQ ID NO 1) and relates these sequence variants to susceptibility to asthma, atopic allergy, and related disorders. This invention also teaches methods that utilize these IL-9 receptor sequence variants for the diagnosis of susceptibility or resistance to asthma and atopic allergy. In addition, methods are described that use variant IL-9 receptors in the development of pharmaceuticals for asthma which depend on the regulation of IL-9 activity. Inflammation is a complex process in which the body's defense system combats foreign entities. While the battle against foreign entities may be necessary for the body's survival, some defense systems improperly respond to foreign entities, even innocuous ones, as dangerous and thereby damage surrounding tissue in the ensuing battle. Atopic allergy is a disorder where genetic background dictates the response to environmental stimuli. The disorder is generally characterized by an increased ability of lymphocytes to produce IgE antibodies in response to ubiquitous antigens. Activation of the immune system by these antigens also leads to allergic inflammation which may occur after their ingestion, penetration through the skin, or after inhalation. When this immune activation occurs and pulmonary inflammation ensues, this disorder is broadly characterized as asthma. Certain cells are important in this inflammatory reaction in the airways and they include T cells and antigen presenting cells, B cells that produce IgE, and mast cells/basophils that store inflammatory mediators and bind IgE, and eosinophils that release additional mediators. These inflammatory cells accumulate at the site of allergic inflammation, and the toxic products they release contribute to the tissue destruction related to the disorder. Web site: http://www.delphion.com/details?pn=US06602850__ •
Methods of making nucleic acids encoding ribonucleases Inventor(s): Saxena; Shailendra K. (West Orange, NJ) Assignee(s): Alfacell Corporation (bloomfield, Nj) Patent Number: 6,423,515 Date filed: October 14, 2000 Abstract: pET11d-rOnc(Q1, M23L) DNA is subjected to two different site-directed mutations, each using an overlapping PCR protocol. One of the site-directed mutations changes the amino acid residue at position 23 of the encoded protein from leucine to methionine, whereby the encoded protein can be made into ranpirnase by cleaving the N-terminal methionine residue and allowing the adjacent glutamine residue to autocyclize. The other site-directed mutation changes the amino acid residue at position 72 of the encoded protein from serine to cysteine, thereby producing an encoded protein that can be made into a cysteinized ranpirnase by cleaving the N-terminal methionine residue and allowing the adjacent glutamine residue to autocyclize. Excerpt(s): The invention relates to Ribonucleases (RNases), and more particularly relates to ranpirnase. In its most immediate sense, the invention relates to nucleic acids that encode proteins that can be used to produce ranpirnase and an RNase that is highly homologous to it. Ranpirnase is the generic name of an RNase that is produced by Alfacell Corporation (assignee herein) under the registered trademark ONCONASE. Ranpirnase is a protein 104 residues long, with a blocked N-terminal of pyroglutamic acid (
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recombinant DNA technology instead of processing biological material. Additionally, work done at the direction of Dr. Richard Youle of the National Institute of Health has suggested that there would be an advantage to modifying ranpirnase in a particular manner. Dr. Youle is a pioneer in the field of "cysteinizing" therapeutically active RNases (specifically, human pancreatic RNase) with the object of increasing their effectiveness. Dr. Youle conceived the idea of re-engineering an RNase so it could be more easily attached to a targeting molecule, thereby making it possible for the RNase to be delivered to a particular cell receptor where it might be most effective. To achieve this objective, he utilized a property of the amino acid cysteine. Web site: http://www.delphion.com/details?pn=US06423515__ •
Modified milk powder composition Inventor(s): Mawatari; Kazunori (Kanagawa, JP), Shibahara; Susumu (Kanagawa, JP), Shimotori; Kazuhiro (Tokyo, JP), Takeuchi; Makoto (Tokyo, JP), Ueda; Takeo (Kanagawa, JP) Assignee(s): Ajinomoto Co., Inc. (tokyo, Jp) Patent Number: 6,423,335 Date filed: November 3, 2000 Abstract: A composition comprising modified milk powder, and glutamine and/or a peptide containing glutamine. Excerpt(s): The present invention relates to a modified milk powder formula for babies of newly born to nine months old, and modified milk powder for infants of nine months old to three years old. Modified milk powder is ingested as a substitute of mother's milk by many neonates, babies, and infants, and has been widely used as an excellent nourishing means in many countries. On the other hand, since a renal function is not thoroughly reached maturity especially in babies and infants, it is difficult to increase a protein level in a meal, and limitation of proteins is carried out. Therefore, in spite of the intrinsically most remarkable growing period, it is impossible to increase proteins in a meal, which are most important for growth, so that it is difficult to promote further growth of babies and infants with mere commercial modified milk powder. Furthermore, it is known that babies and infants lose little by little an immune antibody (IgG) received from their mother and their resistance to infection gradually decreases at the time exceeding six months after their birth. From this point of view, it is also desirable to actively supplement sufficient nutrition, particularly proteins which positively act on immunity, but the supplementation is difficult from the reason mentioned above, too. Web site: http://www.delphion.com/details?pn=US06423335__
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Modulation of in vivo glutamine and glycine levels in the treatment of autism Inventor(s): McGrew; Susan G. (Nashville, TN), Phillips, III; John A. (Brentwood, TN) Assignee(s): Vanderbilt University (nashville, Tn) Patent Number: 6,362,226 Date filed: December 5, 2000
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Abstract: A method of treating autism in a patient. The method includes administering to the patient an effective amount of a glutamine level reducing agent, a glycine level reducing agent or combinations thereof. Representative glutamine level reducing agents are phenylbutyrate and phenylacetate, and a representative glycine level reducing agent is sodium benzoate. Optionally, an N-methyl-D-aspartate receptor antagonist can also be administered to the patient. A representative N-methyl-D-aspartate receptor antagonist is dextromethorphan. Excerpt(s): The present invention relates to a method for treating autism in patients. More particularly, the present invention relates to a method for modulating in vivo levels of glutamine, glycine or both glutamine or glycine in the treatment of autism. Autism is a developmental disorder characterized by social relating and communicating impairments along with restricted, repetitive or stereotypical behavior and onset by three years of age. A genetic basis for the disorder is suggested by observations such as developmental anomalies in autistic patients, increased incidence of autism in siblings of autistic patients, and a tendency for both of a set of monozygotic twins to be either autistic or not autistic (also called "concordance" for a disorder). However, in 75-80% of autistic individuals, no underlying cause is found for the autism. Previous studies have implicated abnormalities involving neurotransmitters including serotonin, norepinephrine, and histamine in some cases of autism. U.S. Pat. No. 4,994,467 issued Feb. 19, 1991 to Zimmerman discloses a method for treating autism in children by administration of therapeutically effective amounts of a N-methyl-D-aspartate (NMDA) receptor antagonist selected from the group consisting of ketamine and dextromethorphan. Web site: http://www.delphion.com/details?pn=US06362226__ •
Mutant form of a cytotoxic ribonucleolytic protein which allows production by recombinant methods Inventor(s): Ardelt; Wojciech (New City, NY), Boix; Ester (Barcelona, ES), Vasandani; Veena M. (Rockville, MD), Wu; Yon-Neng (Bethesda, MD), Youle; Richard J. (Bethesda, MD) Assignee(s): The United States of America AS Represented by the Department of Health and (washington, Dc) Patent Number: 6,649,392 Date filed: April 4, 1996 Abstract: The present invention provides recombinant Onc (rOnc) compositions and methods. Recombinant Onc proteins of the invention have an amino terminal methionine and comprise an Onc polypeptide. The amino terminal methionine of the protein allows for recombinant production in a bacterial host cell. Cleaving the amino terminal methionine exposes the amino terminal glutamine of the polypeptide. The Onc polypeptide has an amino terminal glutamine. Cyclization of the amino terminal glutamine of the polypeptide to a pyroglutamyl residue provides rOnc polypeptides and proteins have anti-cancer and anti-viral activity. Excerpt(s): The invention relates to methods and compositions for the recombinant production of Onc, a cytotoxic ribonucleolytic protein having anti-tumor and anti-viral properties. In particular, the invention relates to a recombinant Onc protein having an amino terminal methionine and comprising an Onc polypeptide. Unfortunately, since Onc is isolated from oocytes, procurement of an adequate supply is uncertain. Recent
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concerns regarding the availability of the anti-cancer compound taxol illustrate some of the problems of obtaining natural products for use as pharmaceuticals. Similarly, availability of Onc is increasingly problematic in light of the declining population of R. pipiens and the seasonal variation in the supply of its oocytes. Accordingly, what is needed in the art is a means to produce Onc by recombinant methods so as to meet demand for this therapeutic and alleviate the impact on its native source. Further, what is needed is a means to derivatize and alter the sequence of Onc to provide more efficacious compounds. Quite surprisingly, the present invention provides these and other advantages. Web site: http://www.delphion.com/details?pn=US06649392__ •
Nutrient therapy for immuno-compromised patients Inventor(s): Germano; Carl (New City, NY) Assignee(s): Millenium Biotechnologies, Inc. (barnardsville, Nj) Patent Number: 6,503,506 Date filed: August 10, 2001 Abstract: A nutritional supplement is taught for treating chronic debilitating diseases such as HIV/AIDS to overcome conditions of oxidative stress, decreased lean muscle mass, decreased energy production (mitochondrial failure) and support immune function. It comprises orally administrable superoxide dismutase (SOD), preferably SOD/GLIADIN, in combination with other antioxidant/immune support components (Beta Glucans, Nucleotides, Fruit Polyphenols); High Immunoglobin Whey; (undenatured whey), Ornithine alpha ketoglutarate (OKG), Branched Chain Amino Acids and Glutamine to reduce loss of lean muscle mass; and Coenzyme Q 10, D-Ribose and L-Carnitine to provide energy support (decrease mitochondrial failure). Excerpt(s): Unfortunately there appears to be a growing number of people suffering from chronic debilitating diseases characterized by muscle tissue wasting, decreased energy and oxidative stress and immune impairment. Most dramatic of such disease is the major increase in HIV presently infecting over 50 million people. Currently approximately 22 million people have died from the consequences of HIV induced Acquired Immune Deficiency Syndrome (AIDS). HIV attacks the human immune system, weakening the body and reducing the patient's ability to ward off opportunistic infections, ultimately rendering him/her defenseless against diseases that usually and under normal circumstances can be successfully treated. There is no cure for AIDS. Over the years a sizable array of vaccines, antiretroviral drugs, such as AZT and other viral suppressive compounds, have been developed that seek to--if not defeat, at least control the rate at which HIV replicates and thereby slow the progression of the disease, or even arrest it. However, most of these drugs to be effective have to be taken in combination with complicated regimes that need to be followed meticulously and indefinitely. More importantly, the toxic nature of these drugs leads to further decreases in host defense, energy production and increases in oxidative stress furthering the development of the disease. These drugs are expensive and not affordable by many if not most HIV infected persons. Furthermore, even if available and affordable, there presently are no reliable data on the side effects of such long term therapy, or HIV's capacity to mutate into drug resistant strains. Web site: http://www.delphion.com/details?pn=US06503506__
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Polynucleotides encoding a novel glutamine transport ATP-binding protein Inventor(s): Black; Michael Terence (Chester Springs, PA), Burnham; Martin Karl Russel (Norristown, PA), Hodgson; John Edward (Malvern, PA), Knowles; David Justin Charles (Redhill, GB), Lonetto; Michael Arthur (Collegeville, PA), Nicholas; Richard O (Collegeville, PA), Reid, Jr.; Robert H (Norriton, PA), Zarfos; Phillip N (Norristown, PA) Assignee(s): Smithkline Beecham Corporation (phialdelphia, Pa), Smithkline Beecham Plc (gb) Patent Number: 6,346,392 Date filed: July 10, 1997 Abstract: The invention provides Glutamine Transport ATP-Binding Protein polypeptides and DNA (RNA) encoding Glutamine Transport ATP-Binding Protein polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing Glutamine Transport ATP-Binding Protein polypeptides to screen for antibacterial compounds. Excerpt(s): This invention relates to newly identified polynucleotides and polypeptides, and their production and uses, as well as their variants, agonists and antagonists, and their uses. In particular, in these and in other regards, the invention relates to novel polynucleotides and polypeptides of the ATP-Binding Transporters family, hereinafter referred to as "Glutamine Transport ATP-Binding Protein". The Streptococci make up a medically important genera of microbes known to cause several types of disease in humans, including, for example, otitis media, conjunctivitis, pneumonia, bacteremia, meningitis, sinusitis, pleural empyema and endocarditis, and most particularly meningitis, such as for example infection of cerebrospinal fluid. Since its isolation more than 100 years ago, Streptococcus pneumoniae has been one of the more intensively studied microbes. For example, much of our early understanding that DNA is, in fact, the genetic material was predicated on the work of Griffith and of Avery, Macleod and McCarty using this microbe. Despite the vast amount of research with S. pneumoniae, many questions concerning the virulence of this microbe remain. It is particularly preferred to employ Streptococcal genes and gene products as targets for the development of antibiotics. The frequency of Streptococcus pneumoniae infections has risen dramatically in the past 20 years. This has been attributed to the emergence of multiply antibiotic resistant strains and an increasing population of people with weakened immune systems. It is no longer uncommon to isolate Streptococcus pneumoniae strains which are resistant to some or all of the standard antibiotics. This has created a demand for both new anti-microbial agents and diagnostic tests for this organism. Web site: http://www.delphion.com/details?pn=US06346392__
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Pompilid wasp-derived neuropeptides Inventor(s): Itagaki; Yasuhiro (Fussa, JP), Kawai; Nobufumi (Komae, JP), Konno; Katsuhiro (Kanagawa, JP), Takayama; Hiroaki (Tokyo, JP) Assignee(s): Suntory Limited (osaka, Jp) Patent Number: 6,573,243 Date filed: May 19, 2000
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Abstract: The present invention provides a peptide represented by the amino acid sequence formula (A):H-X.sub.1 -X.sub.2 -X.sub.3 -X.sub.4 -Gly-X.sub.6 -X.sub.7 -AspGln-R (A)wherein:each of X.sub.1 and X.sub.3 independently represents Arg or Lys, each of X.sub.2, X.sub.4 and X.sub.6 independently represents Ile or Leu, and X.sub.7 represents Phe, Tyr or Trp; andR represents -NH.sub.2, -Leu-NH.sub.2, -Leu-SerNH.sub.2, -Leu-Ser-Lys-NH.sub.2, -Leu-Ser-Arg-NH.sub.2, -Leu-Ser-Lys-Leu-NH.sub.2, or -Leu-Ser-Arg-Leu-NH.sub.2;and a salt thereof.(In the above, Gly stands for a glycine residue, Asp stands for an aspartic acid residue, Gln stands for a glutamine residue, Arg stands for an arginine residue, Lys stands for a lysine residue, Ile stands for an isoleucine residue, Leu stands for a leucine residue, Phe stands for a phenylalanine residue, Tyr stands for a tyrosine residue, Trp stands for a tryptophan residue, and Ser stands for a serine residue.)The peptide acts on glutamate receptors and is expected to be useful in the treatment of cerebral nerve diseases associated with glutamic acid. Excerpt(s): The present invention relates to novel neuropeptides and more specifically to peptides obtained from the venoms of the solitary wasps Anoplius samariensis and Batozonellus maculifrons, and analogous peptides thereof. Since solitary wasp species such as thread-waisted wasps and pompilid wasps paralyze other insects with their venom, it is believed that the venom contain substances that act on the nervous system. In fact, peptides called mastoparans have been isolated from a certain kind of solitary wasp, and these peptides are used as useful compounds for the study of information transmission system of the living body. On the other hand, various compounds have been isolated in the studies on spider toxins, and it has been confirmed that their effect of paralyzing nerves is based on their inhibitory action on glutamate receptors. Glutamic acid is known to play an important role as an excitatory neurotransmitter mediated by glutamate receptors in the central nervous system (e.g. brain, spinal cord) of mammals, and the synapses of insects and crustaceans. And further, it is known that excess glutamic acid causes over-excitation of nerve cells resulting in death of the nerve cells. Therefore, enhancement of the function of glutamate receptors and conversely temporary blocking of their function are believed to provide therapeutic benefits on cerebral nerve diseases associated with glutamic acid. Web site: http://www.delphion.com/details?pn=US06573243__ •
Preparation of 2-hydroxy-5-oxoproline and analogs thereof Inventor(s): Martinez; Rodolfo A. (Santa Fe, NM), Unkefer; Pat J. (Los Alamos, NM) Assignee(s): The Regents of the University of California (los Alamos, Nm) Patent Number: 6,288,240 Date filed: May 31, 2000 Abstract: The compound 2-hydroxy-5-oxoproline and analogs thereof may be used to produce an increase in carbon dioxide fixation, growth, dry weight, nutritional value (proteins and amino acids), nodulation and nitrogen fixation and photosynthetically derived chemical energy when applied to plants through their roots and/or through their foliar portions. The present invention includes an essentially quantitative chemical synthesis for this compound which is performed in a single step reaction of Fremy's Salt (potassium nitrosodisulphonate) with either glutamine or 2-pyrrolidone-5-carboxylic acid. Fremy's salt (potassium nitrosodisulphonate) is available commercially, or can be readily synthesized.
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Excerpt(s): The present invention relates generally to the preparation of certain prolines and, more particularly, to the preparation of the sodium salt of 2-hydroxy-5-oxoproline. The metabolite 2-hydroxy-5-oxoproline (2-oxoglutaramate) was discovered several decades ago in animal livers and kidneys and investigated in these tissues. A limited understanding of its function in animals was developed from these studies; in cells this material appears to be made by the physiologically irreversible transamination of glutamine. The compound appears to play a role in the regulation of tissue glutamine levels and in ammoniagenesis; that is, the amide nitrogen in glutamine is a major source of urinary ammonia. See, e.g., "The Glutamine Tranaminase-.omega.-Amidase Pathway" by Arthur J. L. Cooper and Alton Meister, CRC Critical Reviews in Biochemistry, pages 281-303, January 1977, and "Occurrence Of Glutamine-2-Oxoacid Transaminase Activity In The Blue-Green Alga ANABAENA CYLINDRICA" by Masayuki Ohmori et al., J. Gen Appl. Microbiol. 31, 171 (1985). More recently, 2hydroxy-5-oxoproline has been found to have significant effect on plant growth. See, e.g., "Use Of Prolines For Improving Growth And Other Properties Of Plants And Algae" by Pat J. Unkefer, Thomas J. Knight, and Rodolfo A. Martinez, U.S. Patent and Trademark Office Ser. No. 09/493,039, filed on Jan. 27, 2000, where the inventors describe the use of the chemical class of compounds known as prolines for improving plant properties and performance. Web site: http://www.delphion.com/details?pn=US06288240__ •
Preparation of fiber, L-glutamine and a soy derivative for the purpose of enhancement of isoflavone bioavailability Inventor(s): Hsu; Charles C. (Long Beach, CA), Hu; Qing-Fu (Laguna Niguel, CA), Paul; Stephen M. (Rancho Santa Margarita, CA), See; Melissa (Long Beach, CA), Shu; Daniel (Laguna Niguel, CA) Assignee(s): Sun Ten Laboratories, Inc. (irvine, Ca) Patent Number: 6,488,968 Date filed: February 22, 2002 Abstract: A method of enhancing phytoestrogen bioavailability and a method for supplementing the dietary needs of warm blooded animals comprising orally administering an effective amount of a dietary supplement composition comprising a phytoestrogen, a fiber and L-glutamine, and optionally N-acetyl-D-glucosamine, in admixture with a biologically acceptable inert carrier. Excerpt(s): This invention relates to nutritional supplements. More particularly, the invention relates to a nutritional supplement composition, and methods of use thereof, to enhance the bioavailability of isoflavone. Nearly 70 years ago, it was reported that certain plants could induce estrus in animals. Subsequently, over 300 plants have been found to possess estrogenic activity (see e.g., Bradbury and White, Vitamin Horm. 12:207 (1954), and Farnsworth et al., J. Pharm. Sci. 64:717(1954)). These compounds have been given the general name of "phytoestrogens" and represent several chemical classes of diphenolic plant compounds that are somewhat related structurally to the mammalian sex hormone 17-beta-estradiol. See Setchell, K. D. R., et al Am. J. Clin. Nutr., 40:569 to 578 (1984). Similarities in the molecular structure of phytoestrogens facilitate binding to the estrogen receptor. An important class of the phytoestrogens is the isoflavone class. Two chemical classes of phytoestrogens are abundant in soybeans, total soy products, and soy protein isolates. Those two classes are coumestrol and isoflavones. The latter class includes daidzein, genistein, glycitein, as well as their
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glycoside and acetylated forms. Phytoestrogens and their metabolites interact with specific cell receptors and compete with endogenous hormone molecules [see Folman, Y. et al, J. Endocr., 44:213 to 218 (1969)], but the biological estrogen-like effect of these compounds is relatively weak. See Kaziro, R. et al, J. Endocr., 103:395 to 399 (1984) and Tang, B. Y. et al, J. Endocr. 85:291 to 297 (1980). Phytoestrogens can induce two different effects in an organism. When the level of endogenous sex hormones is relatively high, the antiestrogenic effect prevails. There are several mechanisms of antiestrogenic activity of the phytoestrogens, including feedback inhibition at the hypothalamus and pituitary gland, and competition and blockade of cell receptors. It has been observed that a phytoestrogen and lignan-rich diet is associated with a reduction in free plasma estradiol, and in reduction of the risk of breast cancer. See Adlercreutz, H. et al, J. Steroid. Biochem., 27:1135 to 1144 (1987) and Mousavi, Y. et al, Steroids, 58:301 to 304 (1993). On the other hand, in postmenopausal women, phytoestrogens can provoke an estrogenic response. See Adlercruetz, H. et al, Lancet, 339:1233 (1992). This dual effect of weak estrogens is demonstrated, and well known "partial" antigens such as Tamoxifen have these properties. Web site: http://www.delphion.com/details?pn=US06488968__ •
Probiotic formulation Inventor(s): Watson; Brenda F. (Tarpon Springs, FL), Watson; Tommy Stanley (Tarpon Springs, FL) Assignee(s): Renew Life, Inc. (clearwater, Fl) Patent Number: 6,468,525 Date filed: August 10, 1999 Abstract: A probiotic formulation, useful as a food supplement and a material for reestablishing beneficial bacteria to the body's intestinal tract, comprises a mixture of beneficial probiotic microflora comprising lactobacillus acidophilus, bifidobacterium bifidum, lactobacillus salivarius, bifidobacterium infantis, and bifidobacterium longum, fructooligosaccharides, L-glutamine, and N-acetyl glucosamine. Excerpt(s): The present invention relates generally to a probiotic formulation. More particularly, the invention is directed to a food supplement formulation comprising five specific microflora and additional ingredients which work together to support the body's ability to replace mucosal linings such as those found in the digestive tract. Probiotic formulations have been used as dietary supplements for many years. Hundreds of different strains of probiotics exist, but only a select few (about 50) of these strains have been tested for efficacy. Beneficial probiotics are categorized as either resident or transient. Resident probiotic bacterial strains live and reproduce in each person's digestive tract. Transient probiotic bacterial strains typically are introduced into the body through ingested food or by means of dietary supplements; however, they do not reproduce nor stay within the digestive system. Probiotic bacteria which normally inhabit the digestive tract reduce the levels of harmful bacteria which may be introduced to the body. For example, naturally occurring probiotic bacteria reduce levels of E. Coli and Salmonella by producing metabolic acid products, e.g., hydrogen peroxide, lactic acid, and acetic acid, that inhibit or antagonize these harmful bacteria. Probiotics also inhibit the levels of harmful microbial pathogens, by lowering the pH in the intestines. This production of organic acids effectively lowers intestinal pH to a level that is favorable for beneficial bacteria and destructive to pathogens. Probiotic bacteria also prevent the establishment of harmful fungus and parasites, such as Candida
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albicans and Giardia lamblia, which became attached to the walls of the colon. Probiotic bacteria can reduce the levels of toxic byproducts such as indole, skatole, and methane produced by the metabolic reaction of harmful bacteria to certain foods. Probiotics also assist the body's digestion of lactose and dietary carbohydrates. Finally, probiotic bacteria can aid the synthesis of B vitamins such as folic acid, niacin, pantothenic acid, and biotin. Web site: http://www.delphion.com/details?pn=US06468525__ •
Process for differential diagnosis of Alzheimer's dementia and device therefor Inventor(s): Jackowski; George (Kettleby, CA), Takahashi; Miyoko (North York, CA) Assignee(s): Syn X Pharma (ca) Patent Number: 6,451,547 Date filed: April 25, 2001 Abstract: A method for diagnosing Alzheimer's disease(AD) is disclosed. The method involves directly detecting the presence of a biochemical marker, specifically human glutamine synthetase, in bodily fluid, preferably blood or a blood product. The detection is by an immunoassay incorporating an antibody specific to human glutamine synthetase. In addition, a method for distinguishing between AD and non-AD dementia is disclosed. Excerpt(s): The present invention relates to a method for the diagnosis of Alzheimer's dementia (AD). The invention particularly relates to a process for quantifying the presence of at least one biochemical marker associated with Alzheimer's dementia. More particularly, the invention relates to a point-of-care immunoassay which utilizes unique antibodies to enable the differential diagnosis of Alzheimer's versus non-Alzheimer's forms of dementia. The social impact of this disease is enormous, caused by the burden placed on caregivers, particularly in the latter stages of the disease. The substantial economic costs are largely related to supportive care and institutional admission. The rapidly increasing proportion of elderly people in society means that the number of individuals affected with AD will grow dramatically, therefore finding an early accurate diagnosis and a cure for AD is becoming an issue of major importance world wide. When an individual is suspected of AD, several recommended tests are performed: (1) Mini Mental State Examination (MMSE)--an office-based psychometric test in the form of a Functional Assessment Questionnaire (FAQ) to examine the scale for functional autonomy, (2) Laboratory tests--complete blood count, measurement of thyroid stimulating hormone, serum electrolytes, serum calcium and glucose levels, (3) Neuroimaging--most commonly used is computed tomography (CT) which has a role in detecting certain causes of dementia such as vascular dementia (VaD), tumor, normal pressure hydrocephalus or subdural hematoma. However, neuroimaging is less effective in distinguishing AD or other cortical dementias from normal aging. In primary care settings, some suggest that CT could be limited to atypical cases, but others recommend routine scanning. Magnetic resonance imaging (MRI) currently offers no advantage over CT in most cases of dementia. Web site: http://www.delphion.com/details?pn=US06451547__
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Serum-and steroid-free culture media for cerebellar granule neurons Inventor(s): Belcher; Scott M. (5824 Lee Ave., Little Rock, AR 72205) Assignee(s): None Reported Patent Number: 6,506,576 Date filed: August 9, 2001 Abstract: The invention is a system for maintenance and high-throughput analysis of cerebellar granule neurons in tissue culture plates under chemically defined conditions. The invention includes serum-free granule culture medium, which is composed of high glucose Dulbecco's Modified Eagle Media (DMEM), NaHCO3, sodium pyruvate, and HEPES, which is subsequently adjusted to pH 7.2. The HEPES buffered DMEM is then supplemented with L-glutamine, KCl, bovine albumin, insulin, transferrin, selenium, penicillin, and streptomycin. Unlike proprietary neuronal culture media, this invention does not include any serum, steroid hormones, phenol red, or added anti-oxidants. The serum-free granule culture medium is then placed in conventional poly-lysine coated tissue culture plates in order to conduct subsequent assays. The invention also includes the ability to package the complete neuronal culture system into a "kit" for isolation, maintenance, treatment, and analysis of cerebellar neurons. A kit would include all the necessary culture medium preparations, tissue culture plates with an appropriate cellular attachment matrix, reagents, disposables and protocols. The kit could be used to evaluate neuronal viability, growth, the role of steroid hormones on neuronal function, drug or toxicant-induced changes in gene expression, or other bioassays. In addition, the invention will be useful in the field of pharmocogenomics because of the ability to analyze small sample sizes. Excerpt(s): The present invention relates to neuronal culture media that may be used for high-throughput analyses. The ability to maintain isolated neurons in primary culture has been critical in advancing our understanding of the functional basis of the nervous system. In primary neuronal culture studies, the use of defined culture conditions is essential for controlling the concentration of components, such as hormones and growth factors, which may affect the growth and development of cultured neurons. Primary cultures of cerebellar neurons are an important in vitro model system that has been used because of their small size, the ease with which large numbers of cells can be isolated, and the resulting physical properties. Neonatal rat or mouse cerebellar granule cells are convenient and frequently used in studies with aims ranging from the identification of factors involved in neurogenesis, development, and migration to defining mechanisms of neurotoxicity and cell death (Cull-Candy, et al., J Physiol, 400: 189-222, 1988; Pemberton, et al. J Physiol, 510: 401-420, 1998; Bhave et al., J Neurosci, 19: 3277-3286, 1999). Because cultured granule cells express both Ca.sup.++ permeable-NMDA and non-NMDA glutamate receptors, these neurons are also an important model used for the analysis of neuronal excitotoxicity (Carroll et al., Neurochem Int, 33: 23-28, 1998; Lim and Ho, J Neurochem, 69: 581-593, 1998). Web site: http://www.delphion.com/details?pn=US06506576__
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Supplement for restoring growth hormone levels Inventor(s): White; Philip (Kelowna, CA) Assignee(s): International Health Products and Services Ltd. (bridgetown, Bb) Patent Number: 6,346,264 Date filed: April 27, 2000 Abstract: A nutritional supplement for ingestion by humans for restoring growth hormone levels consisting of branched chain amino acids chosen from the group leucine, isoleucine, and valine; and free form amino acids chosen from the group lysine, glutamine, ornithine, arginine, and glycine. Excerpt(s): This invention relates to the field of nutritional supplements, including supplements which elevate release of human growth hormone. Until recently human growth hormone (hereinafter alternatively referred to as hGH) was available only in expensive injectable forms and benefits from the restoration of hGH levels available only to those with the ability to pay. Most recently natural substances which can trigger the release of human growth hormone from an individual's own anterior pituitary gland have become available. These are generically referred to as secretagogues. Secretagogues have the ability to restore hGII levels, potentially to the levels found in youth. See for reference the book entitled "Grow Young With hGII" by Dr. Ronald Klatz, President of the American Academy of Anti-Aging, published in 1997 by Harper Collins. Franco Salomon et al [The New England Journal of Medicine Vol. 321 (26) p.1797-1803) 1989] carried out a 6 month randomized, double blind, placebo controlled trial of recombinant human growth hormone on 24 patients suffering from growth hormone deficiency. They noticed an increase in Insulin-like Growth Factor 1 ("IGF-1"), lean body mass and reduction in fat. Metabolic rate was increased and plasma cholesterol lowered. Web site: http://www.delphion.com/details?pn=US06346264__
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Therapeutic micronutrient composition for severe trauma, burns and critical illness Inventor(s): Sherratt; J. Dale (Boston, MA), Somerville; Joann A. (Reading, MA) Assignee(s): Baxter International, Inc. (deerfield, Il) Patent Number: 6,391,332 Date filed: April 20, 2000 Abstract: Compositions comprising glutamine in combination with other micronutrients, for example, N-acetyl-cysteine, L-arginine, and Vitamins A, C, D, E are disclosed. Such compositions can be administered to enhance recovery of patients with severe trauma, burns, injury, infection and for promoting wound healing. Excerpt(s): The present invention relates to the use of the amino acid glutamine in combination with additional micronutrients in a composition for treating stress responses associated with severe trauma, bums, injury, infection and for promoting wound healing. Major injury, burns, trauma, infection, or any critical illness, characteristically lead to profound metabolic abnormalities, lean mass catabolism, ongoing oxidant induced tissue damage, immune deficiency states and impaired wound healing. The metabolic abnormalities lead to increased cell energy demands and inefficient nutrient utilization. Tissue damage is observed as progressive lipid peroxidation. An immune deficiency state can lead to increased infections. The addition of micronutrients to a patient's therapeutic regime enhances recovery from severe stree
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induced responses caused by injury, burns, or sepsis. Micronutrients are essential for cellular function and the addition of such to a patient with metabolic derangement and ongoing catabolism will enhance recovery. The present invention comprises a micronutrient composition in unit dosage form comprising L-glutamine, L-arginine, Nacetyl-cysteine, vitamin A, vitamin C, vitamin E, Thiamin, riboflavin, niacin, vitamin B.sub.6, folate, vitamin B.sub.12, pantothenic acid, magnesium, zinc, selenium and copper. Web site: http://www.delphion.com/details?pn=US06391332__ •
Therapeutic nutrient regimen for alleviating mucositis, stomatitis and cachexia in oncology patients Inventor(s): Sherratt; J. Dale (Sherborn, MA), Somerville; Joann (Reading, MA) Assignee(s): Baxter International Inc. (deerfield, Il) Patent Number: 6,479,068 Date filed: June 30, 2000 Abstract: The present invention relates to a daily regimen for oncology patient suffering from mucositis, stomatis, and cachexia wherein the daily regimen involves administering to the patient at least one dose of an oral composition in unit dosage form which comprises L-glutamine, vitamin A, vitamin C, vitamin E, and selenium; and at least four glutamine lozenges throughout the day which comprises about 2 grams of glutamine each, beginning 4-7 days prior to said treatment and continuing through said treatment. Excerpt(s): The present invention relates to the use of the amino acid glutamine in combination with additional nutrients in a composition for alleviating side effects of oncology treatment in a cancer patient comprising administering to the patient a daily regimen which comprises administering (a) at least one dose of an oral composition in unit dosage form which comprises L-glutamine, vitamin A, vitamin C, vitamin E, and selenium twice daily; and (b) at least four glutamine lozenges throughout the day which comprise about 2 grams of glutamine each, beginning 4-7 days prior to said treatment and continuing through said treatment. The daily regimen allows for physical contact of mucosal membranes with glutamine as well as systemic administration for alleviating the side effects of oncology therapy. Skubitz et al. in U.S. Pat. Nos. 5,438,075 and 5,545,668 disclose an oral glutamine composition which is used to treat oropharyngeal mucositis in patients undergoing chemotherapy or radiotherapy. The patents disclose a method of alleviating stomatitis or esophagitis originating from treatment with chemotherapy and/or radiotherapy by administering the glutamine composition described in the patent. Anderson et al. disclose a patient study involving administration of a glutamine suspension to swish and swallow on days of chemotherapy administration and for at least 14 additional days. Anderson et al. conclude that low dose oral glutamine supplementation during and after chemotherapy significantly reduced both the duration and severity of chemotherapy-associated stomatitis and decreased the chance of patients developing mouth sores as a consequence of intensive cancer chemotherapy. See Anderson et al., Cancer, vol. 83 pages 1433-9 (1998). Web site: http://www.delphion.com/details?pn=US06479068__
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Use of metal complexes to treat gastrointestinal infections Inventor(s): Chevalier; Sylvaine Francoise Aline (Surbiton, GB), Phillips; Rosemary Helen (London, GB), Powell; Jonathan Joseph (London, GB), Thompson; Richard Paul Hepworth (London, GB) Assignee(s): Pfylori Limited (london, Gb) Patent Number: 6,552,072 Date filed: January 11, 2001 Abstract: Compositions and methods for treating gastrointestinal symptoms and gastrointestinal microbes are provided. In accordance with the method, a dietary metal and a dietary ligand are administered, wherein the dietary metal is zinc, copper, cobalt, manganese or iron and the dietary ligand is ascorbate, aspartate, citrate, histidine, malate, maltol, gluconate, glutamate, glutamine, succinate, tartrate, or a combination thereof. Excerpt(s): The present invention relates to novel therapies to treat gastrointestinal symptoms and gastrointestinal microbes. In particular, therapies are provided for common gastrointestinal symptoms such as dyspepsia and non-infectious diarrhoea and for common gatrointestinal infections such as Helicobacter pylori and Salmonella. The use of complexes of dietary metals in preparing therapeutic agents for use in such methods is also provided. Gastrointestinal infections cause widespread diarrhoea and debility and account for a large proportion of antibiotic use worldwide. The nonspecificity of antibiotics has meant that resistant pathogens are an increasing problem leading to more complex treatments. Furthermore, many antibiotics have side effects that reduce compliance, while cost may preclude their use in developing countries where infections are more common. Even in the western world complex treatment is often required, for example, H. pylori infection of the gastric mucosa requires "triple therapy" for successful eradication. There are however few gut-specific antimicrobials and antibiotics designed for absorption and systemic action are mainly used. Toxic metal compounds have been in use for some considerable time in the treatment of gastrointestinal symptoms and of gastrointestinal and even systemic infections, but significant side effects occur, such as the encephalopathy seen with bismuth complexes (Gorbach S. L., Gastrenterology, 99:863-875 (1990)). Newer "colloidal" bismuth compounds such as De-Noltab.TM. (bismuth sub-citrate) and Pepto-Bismol.TM. (bismuth sub-salicylate) are not well absorbed in man and have some activity against gastrointestinal bacteria. However, it has been shown that significant and prolonged plasma levels of bismuth are found following ingestion of such preparations (Nwokolo er al, Alimentary, Pharmacology and Therapeutics, 4:163-169 (1990)) (up to 135.mu.g/l for De-Noltab.TM. and 5.mu.g/l for Pepto-Bismol.TM.). Web site: http://www.delphion.com/details?pn=US06552072__
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Use of prolines for improving growth and other properties of plants and algae Inventor(s): Knight; Thomas J. (Portland, ME), Martinez; Rodolfo A. (Santa Fe, NM), Unkefer; Pat J. (Los Alamos, NM) Assignee(s): The Regents of the University of California (los Alamos, Nm) Patent Number: 6,555,500 Date filed: April 16, 2002
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Abstract: Increasing the concentration of prolines such as 2-hydroxy-5-oxoproline, in the foliar portions of plants has been shown to cause an increase in carbon dioxide fixation, growth rate, dry weight, nutritional value (amino acids), nodulation and nitrogen fixation, photosynthetically derived chemical energy, and resistance to insect pests over the same properties for wild type plants. This can be accomplished in four ways: (1) the application of a solution of the proline directly to the foliar portions of the plant by spraying these portions; (2) applying a solution of the proline to the plant roots; (3) genetically engineering the plant and screening to produce lines that overexpress glutamine synthetase in the leaves which gives rise to increased concentration of the metabolite, 2-hydroxy-5-oxoproline (this proline is also known as 2-oxoglutaramnate); and (4) impairing the glutamine synthetase activity in the plant roots which causes increased glutamine synthetase activity in the leaves which gives rise to increased concentration of 2-hydroxy-5-oxoproline. Prolines have also been found to induce similar effects in algae. Excerpt(s): The present invention relates generally to growth of plants and algae and, more particularly, to the use of the chemical class of compounds known as prolines for improving the properties and performance of plants and algae. Many agricultural activities are time sensitive, with costs and returns being dependent upon rapid turnover of crops or upon being first to reach the market place. Therefore, rapid plant growth is an economically important goal for many agricultural businesses that grow high-value crops such as vegetables, berries, and bananas, as well as for the greenhouse and nursery businesses. The importance of improved crop production technologies has increased as a result of the observation that yields for many well-developed crops have tended to plateau in recent years. The goal of rapid plant growth has been addressed in numerous studies of plant regulatory mechanisms, which remain incompletely understood. In particular, a complete understanding has not been attained for the plant regulatory mechanisms that coordinate carbon and nitrogen metabolism, which must have a major impact on plant growth and development. The metabolism of carbon and nitrogen in photosynthetic organisms must be regulated in a coordinated manner to assure efficient use of plant resources and energy. Understanding of carbon and nitrogen metabolism now includes details of certain steps and metabolic pathways which are subsystems of larger systems. In photosynthetic organisms, carbon metabolism begins with CO.sub.2 fixation which includes two major processes termed C-3 and C-4 metabolism. In plants with C-3 metabolism the enzyme, ribulose bisphosphate carboxylase (RuBisCo) catalyzes the combination of CO.sub.2 with ribulose bisphosphate to produce 3-phosphoglycerate, a three carbon compound (C-3), that the plant uses to synthesize carbon-containing compounds. In plants with C-4 metabolism, CO.sub.2 is combined with phosphoenol pyruvate to form acids containing four carbons (C-4) in a reaction catalyzed by the enzyme phosphoenol pyruvate carboxylase. The acids are transferred to the bundle sheath cells where they are decarboxylated to release the CO.sub.2 which is then combined with ribulose bisphosphate In the same reaction as employed by C-3 plants. In photosynthetic organisms, nitrogen is assimilated by the action of the enzyme glutamine synthetase which catalyzes the combination of ammonia with glutamate to form glutamine. Web site: http://www.delphion.com/details?pn=US06555500__
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Patent Applications on Glutamine As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to glutamine: •
Adapted NS0 cell lines with the ability to grow under glutamine-free conditions Inventor(s): Burky, John E.; (Newark, CA), Sauer, Paul W.; (Fremont, CA) Correspondence: Howrey Simon Arnold & White, Llp; Box 34; 301 Ravenswood AVE.; Menlo Park; CA; 94025; US Patent Application Number: 20040002135 Date filed: March 10, 2003 Abstract: The present invention provides for an adapted NS0 myeloma cell line that has the ability to grow in glutamine-deficient or glutamine-free condition. In one particular embodiment, the adapted NS0 cell line has an Accession Number ATCC No. PTA-4106. Excerpt(s): This application claims the benefit of priority of the U.S. provisional application U.S.S No. 60/368,552 filed Mar. 28, 2002, which is incorporated by reference in its entirety. This invention relates to the field of cell culture technology. In particular, it relates to a NS0 mycloma cell line that has the ability to grow in glutamine-free cell culture media, and thereby reduce ammonia toxicity associated with glutamine metabolism. In one example, the adapted NS0 cell line has an Accession Number ATCC No. PTA-4106. Ammonia is known to be a toxic byproduct of glutamine metabolism. Its accumulation has adverse effect on cell culture performance such as reduced growth rates, changes in metabolic rates, perturbation of protein processing, and virus replication. Ammonia can be produced during cell culture by two separate pathways involving glutamine glutaminolysis (metabolism) and glutamine deamidation (chemical breakdown). Therefore, glutamine provides the main source of ammonia. (Chen, et al., Chin. J. Biotechnol. 8(4): 255-61 (1992)). Accordingly, eliminating glutamine entirely from the cell culture media would significantly reduce ammonia production. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Alkaline protease Inventor(s): Izawa, Yoshifumi; (Haga-gun, JP), Kobayashi, Tohru; (Haga-gun, JP), Nomura, Masafumi; (Wakayama-shi, JP), Okuda, Mitsuyoshi; (Haga-gun, JP), Saeki, Katsuhisa; (Haga-gun, JP), Saito, Kazuhiro; (Haga-gun, JP), Sato, Tsuyoshi; (Haga-gun, JP), Sumitomo, Nobuyuki; (Haga-gun, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20040002432 Date filed: March 12, 2003 Abstract: Provided in the present invention is an alkaline protease wherein an amino acid residue at (a) position 65, (b) position 101, (c) position 163, (d) position 170, (e)
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This has been a common practice outside the United States prior to December 2000.
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position 171, (f) position 273, (g) position 320, (h) position 359 or (i) position 387 of SEQ. ID NO: 1 or at a position corresponding thereto has been selected from the following amino acid residues: position (a): proline, position (b): asparagine, position (c): histidine, aspartic acid, phenylalanine, lysine, asparagine, serine, isoleucine, leucine, glutamine, threonine and valine, position (d): valine and leucine, position (e): alanine, glutamic acid, glycine and threonine, position (f): isoleucine, glycine and threonine, position (g): phenylalanine, valine, threonine, leucine, isoleucine and glycine, position (h): serine, leucine, valine, isoleucine and glutamine, position (i): alanine, lysine, glutamine, glutamic acid, arginine and histidine.The present invention makes it possible to efficiently produce and provide alkaline proteases having activity even in the presence of a highly concentrated fatty acid, and exhibiting excellent detergency for the removal of a complex stain containing protein, sebum and the like, and therefore being useful as an enzyme to be incorporated in a detergent. Excerpt(s): The present invention relates to an alkaline protease useful as an enzyme incorporated in a detergent, and a gene encoding the same. Use of protease in industrial fields has a long history and has spread widely to various fields including detergents such as laundry detergents, fiber modifiers, leather treating agents, cosmetic compositions, bath additives, food modifiers, and pharmaceuticals. Of these, proteases for detergents are produced industrially in the largest amount. Known are, for example, Alcalase (trade mark; product of Novozymes), Savinase (trade mark; product of Novozymes), Maxacal (trade mark; product of Genencor), Blap (trade mark; product of Henkel), and KAP (product of Kao). Proteases are incorporated into detergents for the purpose of degrading stains, which are composed mainly of proteins adhered to clothes. In practice, stains contain not only proteins but also plural components having, mixed therein, organic matters and inorganic matters such as lipids derived from sebum and solid particles. There is accordingly a demand for the development of detergents having detergency high enough to remove such a complex stain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Anticancer polypeptide-metal complexes and compositions, methods of making, and methods of using same Inventor(s): Xu, Jing Ya; (Missouri City, TX), Yang, David J.; (Sugar Land, TX), Yu, Dongfang; (Houston, TX), Zuo, William W.; (Sugar Land, TX) Correspondence: J. M. (mark) Gilbreth; Gilbreth & Associates, P.C.; P.O. Box 2428; Bellaire; TX; 77402-2428; US Patent Application Number: 20030109432 Date filed: December 10, 2001 Abstract: Novel drug complexes comprising a polypeptide carrier moiety comprising glutamic acid and at least one of the group consisting of aspartic acid, alanine, asparagine, glutamine, glycine, and any combinations thereof, are disclosed. The drug moiety is a therapeutic metal selected from the group consisting of platinum, iron, gadolinium, rhenium, manganese, cobalt, indium, gallium or rhodium. Methods for making said complexes, compositions comprising said complexes, methods for making saiduch compositions, and methods for treating a patient comprising use of said complexes and/or compositions are further disclosed. Excerpt(s): The present invention relates to polypeptide-transition-metal complexes. In another aspect, the present invention relates to methods for making such polypeptide-
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transition metal complexes. In even another aspect, the present invention relates to compositions comprising polypeptide- transition-metal complexes and method of making such compositions. In still another aspect, the present invention relates to methods of using such polypeptide-transition-metal complexes and compositions comprising such complexes to treat a patient afflicted with a condition, such as for example a cancer in any stage of development. Improvement of cancer treatment is extensively determined by the development of more tumor specific pharmaceuticals and new drug delivery techniques. Due to an angiogenesis process involved in the tumor vasculature density and permeability, cell cycle regulation and cell signalling agents have opened a new era in the treatment of various tumors and undergone extensive development and evaluation. Despite the outstanding advances made in the field of pharmacology, some significant limitations still remain in the treatment of various diseases via drug agents. One of the most significant limitations at this time relates to the delivery of particular drugs in vivo, especially in situations where drugs are poorly water soluble. Indeed, the use of some drugs which show great promise in vitro, has been severely limited due to issues related to their solubility. This causes problems with drug delivery in vivo. One example of such a drug is cisplatin in the treatment of solid tumors. As discussed below, the prior art has attempted to address this issue in a number of ways. However, as presented in more detail below, prior to the instant invention, the unique advantages of conjugating a transition-metal drug to one of the inventive polypeptides, while desired, were unknown. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biologic variability of asthma associated factors useful in treating and diagnosing atopic allergies including asthma and related disorders Inventor(s): Grasso, Luigi; (Philadelphia, PA), Holroyd, Kenneth J.; (Collegeville, PA), Levitt, Roy Clifford; (Ambler, PA), Nicolaides, Nicholas C.; (Boothwyn, PA) Correspondence: Morgan Lewis & Bockius Llp; 1111 Pennsylvania Avenue NW; Washington; DC; 20004; US Patent Application Number: 20030143687 Date filed: December 17, 2002 Abstract: This invention relates to the diagnosis, treatment and methods for discovery of new therapeutics for atopic asthma and related disorders based on variants of Asthma Associated Factor 2. One embodiment of the invention is a variant of AAF2 wherein codon 173 is deleted resulting in the loss of glutamine 173 from the mature protein precursor. This single amino acid deletion results in a non-functional AAF2 protein and therefore the presence of this phenotype should be associated with less evidence of atopic asthma. Correspondingly, the lack of susceptibility to an asthmatic, atopic phenotype is characterized by the loss of glutamine at codon 173. The invention includes isolated DNA molecules which are variants of the wild type sequence as well as the proteins encoded by such DNA and the use of such DNA molecules and expressed protein in the diagnosis and treatment of atopic asthma. Excerpt(s): This application is related to U.S. Provisional Application Serial No. 60/032,224 which was filed Dec. 2, 1996, and is incorporated by reference. It is also related to the subject matter of U.S. patent application Ser. Nos. 08/697,419, 08/697,360, 08/697,473, 08/697,472, 08/697,471, 08/702,105, 08/702,110, 08/702,168 and 08/697,440 all of which were filed on Aug. 23, 1996, and 08/874,503 filed on Jun. 13, 1997, and are herein incorporated by reference. This invention describes biologic variability in the IL-9
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receptor (Asthma Associated Factor 2) (SEQ ID NO1) and relates these sequence variants to susceptibility to asthma, atopic allergy, and related disorders. This invention also teaches methods that utilize these IL-9 receptor sequence variants for the diagnosis of susceptibility or resistance to asthma and atopic allergy. In addition, methods are described that use variant IL-9 receptors in the development of pharmaceuticals for asthma which depend on the regulation of IL-9 activity. Inflammation is a complex process in which the body's defense system combats foreign entities. While the battle against foreign entities may be necessary for the body's survival, some defense systems improperly respond to foreign entities, even innocuous ones, as dangerous and thereby damage surrounding tissue in the ensuing battle. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Biological material and uses thereof Inventor(s): Pantelidis, Panagiotis; (London, GB) Correspondence: Needle & Rosenberg P C; 127 Peachtree Street N E; Atlanta; GA; 303031811; US Patent Application Number: 20030175898 Date filed: December 16, 2002 Abstract: The present invention provides an isolated nucleic acid molecule having a variation of the IL-13 encoding sequence shown in FIG. (1) wherein the variation is at least one of G to C at position +543nt and/or C to T at position +1922nt and/or G to A at position +2043nt and/or C to A at position +2579nt upstream of the initiation codon. The invention further provides an isolated amino acid sequence encoding a variant IL13 containing glutamine at amino acid position 130, and the use of said amino acid sequence in a method of producing an antibody. Additionally, there is provided a method of detecting susceptibility or resistance to a disorder associated with an immune response comprising testing nucleic acid from an individual for the presence of a variation in the nucleotide sequence encoding IL 13. Excerpt(s): This invention relates to variants of the nucleic acid sequence encoding Interleukin 13 (IL-13) and the use of such sequence variants in medicine, especially in the diagnosis of susceptibility or resistance to disorders associated with an immune response, particularly the inflammatory response associated with asthma, atopic allergy and latex sensitisation. Numerous studies have demonstrated that CD4.sup.+T lymphocytes, via the release of specific cytokines, regulate the inflammatory response observed in asthma (for example, see Robinson D, Hamid Q, Bentley A, Ying S, et al. (1993) Journal Of Allergy And Clinical Immunology 92: 313-24; Robinson D S, Ying S, Bentley A M, Meng Q, et al. (1993) Journal Of Allergy And Clinical Immunology 92: 397403; Robinson D S, Hamid Q, is Ying S, Tsicopoulos A, et al. (1992) New England Journal of Medicine 326: 298-304; Ying S, Durham S R, Corrigan C J, Hamid Q, et al. (1995) American Journal Of Respiratory Cell And Molecular Biology 12: 477-87). The T helper cell type 2 (T.sub.H2) cytokines, which include interleukin-4 (IL-4), IL-5 and IL-10 have been implicated in the development of allergic inflammation. High expression of these cytokines has been observed in the bronchoalveolar lavage (BAL) cells and bronchial biopsies of asthmatic patients (Robinson D, Hamid Q, Bentley A, Ying S, et al. (1993) Journal Of Allergy And Clinical Immunology 92: 313-24; Robinson D S, Ying S, Bentley A M, Meng Q, et al. (1993) Journal Of Allergy And Clinical Immunology 92: 397403; Robinson D S, Hamid Q, Ying S, Tsicopoulos A, et al. (1992) New England Journal of Medicine 326: 298-304; Ying S, Durham S R, Corrigan C J, Hamid Q, et al. (1995)
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American Journal Of Respiratory Cell And Molecular Biology 12: 477-87). IL-13 is biologically closely related to IL4 and shares signal transduction elements as well as receptor components with IL4 (Punnonen J, Aversa G, Cocks B G, McKenzie A N J, et al. (1993) Proc Natl Acad Sci USA 90:3730-4; McKenzie A N J, Culpepper J A, Malefyt R D, Briere F, et al. (1993) Proc Natl Acad Sci USA 90: 3735-9; Sornasse T, Larenas P V, Davis K A, deVries J E, et al (1996) Journal of Experimental Medicine 184: 473-83; Lefort S, Vita N, Reeb R, Caput D, et al. (1995) FEBS Letters 366: 122-6). It is produced at high levels by CD4+T.sub.H2 cells after activation but has also been found to be produced by other T cell subsets including T.sub.H0 and CD8+T cells (De Waal Malefyt R D, Abrams J S, Zurawski S M, Lecron J C, et al. (1995) International Immunology 7: 1405-16). One of most important similarities with IL-4 is the ability to induce IgE production (Punnonen J, Aversa G, Cocks B G, McKenzie A N J, et al. (1993) Proc Natl Acad Sci USA 90:3730-4; McKenzie A N J, Culpepper J A, Malefyt R D, Briere F, et al. (1993) Proc Natl Acad Sci USA 90: 3735-9; Emson C L, Bell S E, Jones A, Wisden W, et al. (1998) Journal of Experimental Medicine 188:399404; Dolecek C, Steinberger P, Susani M, Kraft D, et al. (1995) Clinical And Experimental Allergy 25:879-89; Punnonen J, Yssel H, deVries J E (1997) Journal Of Allergy And Clinical Immunology 100:792-801). However, unlike IL-4, IL-13 is ineffective in directing T.sub.H2-cell differentiation (Sornasse T, Larenas P V, Davis K A, deVries J E, et al. (1996) Journal of Experimental Medicine 184: 473-83). Evidence suggesting a critical role for IL-13 in asthma comes from a well-characterised experimental murine model of allergic asthma (WillsKarp M, Luyimbazi J, Xu X Y, Schofield B, et al. (1998) Science 282:2258-61; Grunig G, Warnock M, Wakil A E, Venkayya R, et al. (1998) Science 282:2261-3). Sensitization and subsequent challenge of mice with allergen results in airway hyperresponsiveness, eosinophil recruitment, increase in specific IgE, and mucus overproduction. Selective neutralization of IL-13 in these models ameliorates the asthma phenotype through a reduction in airway hyperresponsiveness, mucus secretion and BAL eosinophilia. Daily administration of IL-13 to the airways of nave mice was shown to be sufficient to induce airway hyperresponsiveness, BAL eosinophilia, increased total serum IgE, and goblet cell metaplasia with mucus overproduction (WillsKarp M, Luyimbazi J, Xu X Y, Schofield B, et al. (1998) Science 282:2258-61; Grunig G, Warnock M, Wakil A E, Venkayya R, et al. (1998) Science 282:2261-3). Similarly, the selective expression of IL-13 in the lung of transgenic mice has been shown to cause a mononuclear and eosinophilic inflammatory response, mucus hypersecretion, subepithelial fibrosis, non-specific airway hyperresponsiveness, and increased production of the eosinophil chemoattractant eotaxin (Zhu Z, Homer R J, Wang Z, Chen Q, et al. (1999) J Clin Invest 103:779-88). In humans, increased expression of IL-13 has been observed in bronchial biopsies from atopic asthmatics (Naseer T, Minshall E M, Martin R J, Laberge S, et al. (1997) American Journal Of Respiratory And Critical Care Medicine 155:845-51) and peripheral blood mononuclear cells from atopic patients (Esnault S, Benbernou N, Lavaud F, Shin H C, et al. (1996) Clinical And Experimental Immunology 103:111-8). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Cell culture medium containing growth factors and L-glutamine Inventor(s): da Silva Madureira Mendes, Sandra Claudia; (Gouda, NL), de Bruijn, Joost Dick; (Amersfoort, NL), Tibbe, Gerhardus Johannes M.; (Amersfoort, NL) Correspondence: Banner & Witcoff, LTD.; 28 State Street; 28th Floor; Boston; MA; 02109; US Patent Application Number: 20030017588 Date filed: June 21, 2002 Abstract: The invention relates to a culture medium for culturing cells, in particular human cells in a process for tissue engineering bone. The medium comprises glucose, a mineral, a vitamin, a growth factor and L-glutamine, wherein the L-glutamine is present in a concentration of at least 300 mg/L. Excerpt(s): The need for replacement parts for the human body, in combination with the shortage of donor tissue and/or organs has lead to the production of replacement tissue by seeding cells onto or into a scaffold. Eventually, this should lead to tissue engineered products ready to be implanted to take over the function of missing or injured body parts. The scaffold defines the construct shape and dimensions of the replacement to be implanted. Preferably, it is manufactured of a porous or fibrous biodegradable material, so that the degradation of the scaffold proceeds parallel with accumulation of tissue components (growth and synthesis of extracellular matrix (ECM)). Thus, the function of the scaffold, the provision of shape and strength, will gradually be taken over by the formed tissue components. In view of the fact that cells from allogenic sources are generally rejected, autologous cells isolated from a tissue biopsy from the patient to be treated are preferably used. In order to minimize the size of the biopsy needed and to minimize the time required for cell expansion, the expanded cells have to be first applied in/onto the scaffold in an efficient manner. In addition, the cells should be distributed homogeneously throughout the scaffold, in order to enable continuous neotissue formation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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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)
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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 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
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Compositions of matter containing L-glutamine and pyridoxal-alpha-ketoglut- arate Inventor(s): Jaffe, Russell; (Vienna, VA) Correspondence: Morrison & Foerster Llp; 1650 Tysons Boulevard; Suite 300; Mclean; VA; 22102; US Patent Application Number: 20020188010 Date filed: May 30, 2001 Abstract: Compositions having synergistic effects which make it possible to obtain full beneficial effects of L-glutamine while avoiding the toxic effects that may accompany administration of L-glutamine. This benefit is attained by administration of L-glutamine in conjunction with pyridoxal-alpha-ketoglutarate (PAK). Compositions containing PAK:L-glutamine at a ratio (w/w) of from 1:1 to 1:10 are effective for providing beneficial effects of L-glutamine at nontoxic levels. Excerpt(s): This invention relates to use of beneficial synergistic administration of Lglutamine in conjunction with pyridoxal-alpha-ketoglu- tarate (PAK) to stimulate repair of tissues dependent on high turnover of cells. The use of L-glutamine, a basic amino acid, to provide an energy source for cells having a rapid turnover, such as cells of the mucosa of the intestine, has been known. Patients in need of significant stimulation of growth and repair of intestinal mucosa include those who have undergone surgical resection of the intestine and those suffering from chronic diseases as enteropathy (atrophy of the intestine) and persistent inflammatory bowel syndrome (IBS). Furthermore, certain infectious diseases and treatment modalities such as administration of antibiotics can cause severe damage to the gastrointestinal mucosa. However, large amounts of L-glutamine are needed to achieve clinical results. Concerns have been raised about the high dosages. The build-up of L-glutamate (derived from energy-producing deamination of L-glutamine), which can act as an exitoneurotoxin. The difficulty resulting from this effect has greatly decreased the use of L-glutamine to provide benefit to those needing tissue repair. Hence, there is need for treatment modalities that will provide the benefits of L-glutamine which are not accompanied by the metabolic imbalance and potential toxic side effects seen under prior regimens. While the compositions of the invention may be used for stimulation of growth and repair of other cells which usually undergo rapid replacement in the body, the cells of the intestinal mucosa offer a reliable model that is conventionally used to study stimulation of growth and repair of cells. The instant invention provides compositions having synergistic effects which make it possible to obtain full beneficial effects available using L-glutamine whilst avoiding the toxic effects that may accompany administration of L-glutamine. This benefit is attained by administration of L-glutamine in conjunction with pyridoxal-alpha-ketoglu- tarate (PAK). Compositions containing PAK:L-glutamine at a ratio (w/w) of from 1:1 to 1:10 are effective for providing beneficial effects of L-glutamine at nontoxic levels. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Compounds that selectively bind to expanded polyglutamine repeat domains and methods of use thereof Inventor(s): Burke, James R.; (Chapel Hill, NC), Nagai, Yoshitaka; (Osaka, JP), Strittmatter, Warren J.; (Durham, NC) Correspondence: Myers Bigel Sibley & Sajovec; PO Box 37428; Raleigh; NC; 27627; US Patent Application Number: 20030229019 Date filed: April 14, 2003 Abstract: Compounds that selectively bind to expanded polyglutamine repeats are disclosed. Such compounds are characterized in that they bind to a first polyglutamine peptide consisting of 60 glutamine residues under conditions in which they do not bind to a second polyglutamine peptide consisting of 20 glutamine residues. Conjugates of such compounds, nucleic acids encoding the same, and methods of use thereof are also disclosed. Excerpt(s): This application claims the benefit of U.S. provisional application serial No. 60/189,781, filed Mar. 16, 2000, the disclosure of which is incorporated by reference herein in its entirety. The present invention concerns compounds that selectively bind to expanded CAG repeat regions in DNA which encode expanded polyglutamine regions in certain disease proteins, methods of treatment employing such compounds, and assay procedures employing such compounds. Eight inherited neurodegenerative diseases, including Huntington's disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), spinobulbar muscular atrophy and spinocerebellar ataxia types 1, 2, 3, 6 and 7, are caused by expanded CAG repeats in the coding region of the disease genes (Koshy, B. T. and Zoghbi, H. Y., Brain Pathol 7, 927-942 (1997); Paulson, H. L. and Fischbeck, K. H, Ann Rev Neurosci, 19, 79-107 (1996); Paulson, H. L., Am J Hum Genet 64, 339-3450 (1999)). The CAG codon is translated into glutamine (Q), and the polyglutamine domain is the only region of homology among the eight disease proteins. The length of the repeat is the critical determinant of age-of-disease onset, with repeat length greater than 40 glutamines producing neurodegeneration in seven of the eight diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Delivery of tissue engineering media Inventor(s): Moore, Karen; (Gainesville, FL), Veazey, William S.; (Gainesville, FL) Correspondence: Miles & Stockbridge; Suite 500; 1751 Pinnacle Drive; Mclean; VA; 22102-3833; US Patent Application Number: 20030170285 Date filed: November 13, 2002 Abstract: The delivery of tissue engineering media using an airbrush.William S. Veazey, D M DNov. 7, 2002 1 Average Delivery Values for Cell Delivery Study using Tissue Engineering Media Delivery System Fine Nozzle Medium Nozzle Large Nozzle 312 microns 494 microns 746 microns 6 PSI 86% 87% 94% 8 PSI 76% 82% 93% 10 PSI 65% 86% 89% 14 PSI 60% 66% 69% 18 PSI 37% 62% 56%Procedure: Bovine dermal fibroblasts were delivered into a 6-well tissue culture plate using a Badger 100 G airbrush having fine, medium and large nozzles at air pressures 6, 8, 10, 14 and 18 psi. Cells were delivered in a concentration of 200,000 cells per 1 mL of media; 1 mL of this cell suspension was delivered for each repetition. The cells were washed in Hanks Balanced
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Salt Solution (HBSS) or Phosphate Buffered Saline (PBS). Trypsin (0.25%) was used to detach the cells from the cell culture plate before delivery. Cells were re-suspended in a 50%-50% Dulbecco's Modified Eagle's Medium (DMEM) and F-12 media (one actually purchases the media in this concentration, called DMEM/F12) with 10% Fetal Bovine Serum (FBS), 2 mM L-Glutamine and 0.1 mM 2-Me.It should be stated that cells could be delivered in a variety of media, and one skilled in the art recognizes that one could use HBSS or PBS alone, or could use DMEM/F12 alone, or any other type of vital media to deliver cells.Cell vitality was measured using a trypan blue exclusion assay.Thickness of deposition was not measured. The 1 mL of airbrush delivered media spread in the tissue culture well as media would normally do. Excerpt(s): The invention relates to methods and systems for the delivery of tissue engineering media to sites in or within the body of human or non-human animals. The term, "tissue engineering" as used herein, comprises the repair, replacement, or regeneration of damaged or diseased tissues by the management of cells, the construction of artificial implants, or the manufacture of substitutes. An example is the process known as "tissue induction," whereby 21/2- and 3-dimensional polymer or mineral scaffolds without cells are implanted in a patient. In tissue induction, tissue generation occurs by the ingrowth of surrounding tissue into the structure. In another method known as "cell transplantation", scaffolds are seeded with cells, cytokines, and other growth-related molecules, followed by culturing. The seeded scaffolds are then implanted to induce the growth of new tissue. Cultured cells are infused into a biodegradable or non-biodegradable scaffold, which is implanted directly in the patient, or first cultured in a reactor wherein the cells proliferate before implantation. The cellscaffold construct may be implanted directly in the patient, thus using the patient's body as an in-vivo bioreactor. Once implanted, in-vivo cellular proliferation and, in the case of absorbable scaffolds, concomitant bio-absorption of the scaffold, proceeds. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Deregulation of glutamine PRPP amidotransferase activity Inventor(s): Smith, Janet L.; (Lafayette, IN), Switzer, Robert L.; (Urbana, IL), Zalkin, Howard; (West Lafayette, IN) Correspondence: Barnes & Thornburg; 11 South Meridian; Indianapolis; IN; 46204 Patent Application Number: 20030166166 Date filed: April 3, 2003 Abstract: The present invention is directed methods of purine synthesis using a modified amidotransferase, wherein the modified glutamine PRPP amidotransferase has reduced sensitivity to end-product inhibition of synthesizing purine nucleotides. Excerpt(s): This application is a divisional of U.S. patent application Ser. No. 09/805,294, filed Mar. 13, 2001; which is a continuation application of U.S. patent application Ser. No. 09/150,440, filed Sep. 9, 1998, now U.S. Pat. No. 6,204,041; which claims priority to U.S. Provisional Patent Application Ser. No. 60/058,216, filed Sep. 9, 1997. This invention relates to the deregulation of purine nucleotide biosynthesis. More particularly, this invention is directed to the modification of glutamine phosphoribosylpyrophosphate (PRPP) amidotransferase to decrease end-product inhibition of glutamine PRPP amidotransferase activity. Glutamine PRPP amidotransferase catalyzes the initial reaction in de novo purine nucleotide synthesis and is the key regulatory enzyme in the pathway. Genes encoding glutamine PRPP
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amidotransferase have been cloned from more than 20 organisms including bacteria, eukarya, and archea. In particular, the enzymes from Escherichia coli and Bacillus subtilis have been purified to homogeneity and are well-characterized, including having the X-ray structures determined for these enzyme species. The E. coli and B. subtilis enzymes are both homotetramers and are representative of two classes of glutamine PRPP amidotransferases. Enzymes of the B. subtilis class are synthesized with an NH.sub.2 terminal propeptide and an Fe-S center, whereas enzymes of the E. coli class have neither. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Enzyme-mediated modification of fibrin for tissue engineering: fibrin formulations with peptides Inventor(s): Hubbell, Jeffrey A.; (Zurich, CH), Sakiyama, Shelly E.; (Zurich, CH), Schense, Jason C.; (Zurich, CH) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20030119186 Date filed: March 25, 2002 Abstract: Heparin-binding regions of several proteins, such as neural cell adhesion molecule, fibronectin, laminin, midkine, and anti-thrombin III have been shown to promote neurite extension on two-dimensional surfaces. The effect of heparin-binding peptides on neurite extension through three-dimensional matrices was investigated by culturing embryonic chick dorsal root ganglia (DRG) within fibrin gels containing chemically attached heparin-binding peptide (HBP). The length of neurites within fibrin gels containing cross-linked HBP was increased by more than 70% over extension through fibrin gels containing no peptide. The HBP sequence of antithrombin III was incorporated into the fibrin gel as the C-terminal domain of a bidomain, chimeric peptide; the N-terminal second domain of this peptide contained the.alpha.2-plasmin inhibitor substrate for Factor XIIIa. Factor XIIIa, a transglutaminase, was used to chemically attach the HBP-containing chimeric peptide to the fibrin gels during polymerization. The amount of HBP cross-linked into the fibrin gels was determined, after degradation by plasmin using gel permeation chromatography, to be approximately 8 moles of peptide per mole fibrinogen. A peptide (HBP), where the cross-linking glutamine was replaced with glycine, showed no increase in extension in comparison with fibrin gels. The addition of heparin to the gel precursors resulted in no increase in neurite extension in comparison with fibrin gels. HBPs promote neurite extension by binding to cell surface proteoglycans on the DRG. Excerpt(s): The present invention relates generally to the fields of materials useful in the support of tissue and cell incorporation and growth. More particularly, it concerns particular substrates of protein, such as fibrin, to which bioactive peptides and combinations of peptides are attached. The active domain of many proteins may in some cases be mimicked at least in part through the use of short peptide sequences derived from the active site of the protein (Massia and Hubbell, 1991, Yamada, 1991). Through this method, the activity of a specific protein can be conferred to an otherwise nonactive surface or matrix. This method allows a much higher concentration of active sequences to be immobilized onto a surface than is found naturally. While many peptides have been shown to have a monotonic correlation between density and cellular activity, other peptides are known to reach a maximum activity at a moderate level of peptide density.
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The best example is migration of cells on a surface coated with RGD (SEQ. I.D. NO. 2). If the concentration of RGD (SEQ. I.D. NO. 2) is too high, the surface binds too strongly to the cells, inhibiting cellular migration. However, if the RGD (SEQ. I.D. NO. 2) density is too low, then there is not enough traction for these cells to effectively migrate across the surface, leading to a maximal migration rate at a moderate surface concentration of peptide. (DiMilla, et al., 1991) Unfortunately, there is not very much research of the concentration dependent effect of these peptides in a three dimensional matrix. It is not possible to predict which peptides will show saturating behavior and it is not possible to predict at what peptide concentration maximal benefits will be observed. While individual peptides can partially mimic the effect of the whole protein, the magnitude of this effect is typically lower. This is due to several reasons, including possible changes in conformation, peptide accessibility and changes in solubility between the peptide and the protein. One additional difference is that the interaction between cells and individual proteins or entire extracellular matrix involve simultaneously binding to multiple peptide sequences. (Martin, 1987, Kleinman, et al., 1993) Sometimes these sequences are on the same protein, but often they are on different proteins. In general it is not possible to predict which combinations might interact negatively, which might interact additively and which might interact synergistically. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Feed mass having a modified protein structure for carnivorous animals Inventor(s): Hoff, Kjell Arne; (Sandnes, NO), Thorsen, Fred Hirth; (Hundvag, NO) Correspondence: Vidas, Arrett & Steinkraus, P.A.; 6109 Blue Circle Drive; Suite 2000; Minnetonka; MN; 55343-9185; US Patent Application Number: 20030035861 Date filed: June 4, 2002 Abstract: A method for producing feed for forming into pellets, the pellets produced by the method to be used to feed carnivorous animals. The addition of the enzyme transglutaminase to a feed mass specifically intended for carnivorous fish will catalyze a reaction between the amino acids glutamine and lysine which form part of the protein chains and the raw material of the proteins of the feed, such that a covalent chemical bond is formed between them, which results in shape permanence in the formed, dried, finished pellets, such that the finished pellets do not lose their shape before time of use. Excerpt(s): The present invention relates to a method for the modification of protein structure in finish shaped feed pellets, balls or the like, among other reasons in order to contribute to strengthening the permanence of the pellet shape in granular feeds of this sort. The invention also relates to feedstuff manufactured according to this method for the formation of a shape-permanent feed in pellet form. Many types of animals in breeding, e.g. salmon and trout, are carnivorous (meat-eating). Their natural food consists of insects (for salmon and trout in the freshwater phase), fish and crustaceans. For other carnivorous farmed animals, such as mink and foxes, the feed may also contain the mammalian flesh, for example fresh slaughterhouse waste. Insects and crustaceans have an exoskeleton which i.e. consists of chitin. Chitin is a linear polysaccharide of N-acetyl-D-glucosamine linked by.beta.1.fwdarw.4 bonds. Other structural carbohydrates such as cellulose (.beta.[1.fwdarw.4] D-glycose) and alginate (D-mannuronic acid) are not found in these prey animals, nor do they contain starch ([1>4] D-glycose) as energy stores. Nevertheless, salmon, trout and other carnivorous fish and animals have enzymes (for example, amylase) that are capable of breaking
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down starch in the gut and making it digestible, but they may be less efficient in this respect than herbivorous (plant-eating) fish and animals. In feeds intended for carnivorous fish it is usual to add between 8% and 25% carbohydrates, for example in the form of wheat or maize, as a binding agent. After pressing, but especially after extrusion, the starch in these carbohydrates will form a matrix or base mass which gives the pellets mechanical strength and shape permanance so that the shape of the pellets can be maintained after drying, further processing, storage and transport. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Glutamine rich dietary composition Inventor(s): Ostrom, Steven M.; (Minnetonka, MN) Correspondence: Thomas Hoxie; Novartis Corporation; Patent And Trademark Dept; 564 Morris Avenue; Summit; NJ; 079011027 Patent Application Number: 20030032583 Date filed: July 19, 2002 Abstract: The present invention is an immunostimulatory composition that bolsters or enhances the immune system in injured, diseased, traumatized or otherwise critically ill patients whose own immune system has been compromised thereby. The ready to feed, liquid formulation comprises glutamine which is stabilized and highly bioavailable in the form of a peptide bound glutamine. Other components comprise the free amino acids such as arginine, a nucleobase such as RNA and omega-3 and omega-6polyunsaturated fatty acids. Excerpt(s): The present invention relates to enteral nutritional formulations. More particularly, the present invention comprises enhanced nutritional formulas which not only supply the necessary nutritional vitamins, minerals, proteins and carbohydrates but which also bolster the patient immune system as well. Critically ill or injured tubefed patients have unique nutritional needs that are not met by standard enteral formulas. Surgery, trauma, burns, sepsis and other illnesses or injuries that induce a hypermetabolic response (HMR) alter the patients' nutritional requirements. The HMR alters substrate metabolism, and increases protein and caloric requirements. Nonessential amino acids such as glutamine and arginine become conditionally essential as a result of this altered metabolic state. Because the gut may be compromised as a result of severe illness or injury, a hydrolyzed protein or "peptide" formula may be better absorbed and utilized than an intact protein formula. For patients suffering from the HMR providing an elemental or semi-elemental diet is highly desirable. In recent years, attention has been focused on identifying the biochemicals or nutrients that are missing from commercially available parenteral nutritional products and enteral diets. It has been demonstrated that the addition of nucleic acids (RNA) to defined formula diets fed to animals resulted in improved host defense mechanisms. It has also been shown that when arginine is fed at levels exceeding the body's need for protein synthesis, host defense mechanisms are enhanced. This is evidenced by the increased blastogenesis of lymphocytes in response to mitogens in animals and human; reduced tumor appearance and incidence; and increased receptivity of cells to lymphokines. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Humanized antibodies LB-00503 and LB-00506 specific for human 4-1BB and pharmaceutical compositions comprising said humanized antibodies Inventor(s): Hong, Hyo Jeong; (Taejon, KR), Jang, Hyunsook; (Seoul, KR), Jeong, Jong Keun; (Seoul, KR), Kang, Chang-Yuil; (Seoul, KR), Kang, Young Jun; (Daejon, KR), Kim, Hwadong; (Kyung-gi Province, KR), Park, Jung-Gyu; (Seoul, KR), Park, Mijeong; (Daejon, KR), Park, Sung Sup; (Taejon, KR), Park, Youngwoo; (Daejon, KR), Rha, Geun Bae; (Daejon, KR), Shim, Dong Sup; (Daejon, KR), Yang, Jae-Young; (Daejon, KR), Yoo, Jin-San; (Daejon, KR), Yoon, Hyesung; (Daejon, KR), Yoon, Sung Kwan; (Taejon, KR) Correspondence: Birch Stewart Kolasch & Birch; PO Box 747; Falls Church; VA; 220400747; US Patent Application Number: 20030096976 Date filed: September 4, 2002 Abstract: The present invention relates to humanized monoclonal antibodies LB-00503 and LB-00506, which are specific for human 4-1BB molecules, have high binding affinities and can bind efficiently with activated T cells expressing the 4-1BB molecule, as well as pharmaceutical compositions. Particularly, the present invention provides said humanized antibody LB-00503, which is modified from the humanized antibody Hz4B4-2 and substitutes the 61st amino acid, serine by asparagine in the amino acid residues of 59th.about.61st and said humanized antibody LB-00506, which enhances the antibody binding affinity of said humanized antibody LB-00503 in which 2 amino acid residues of the right border in the antibody binding site CDR2 of the heavy chain variable region are substituted from glutamine (Q)--glycine (G) to lysine (K)--serine (S). Excerpt(s): The invention relates to humanized antibodies that specifically bind to 4-1BB receptor proteins, preferably to human 4-1BB receptor protein. The humanized antibodies can be used as diagnostic reagents or can be formulated into pharmaceutical compositions for administration to a patient. In particular, the present invention relates to humanized antibodies and pharmaceutical compositions comprising humanized antibodies. More particularly, the present invention relates to humanized monoclonal antibodies LB-00503 and LB-00506 which are specific for human 4-1BB molecule, have high binding affinities, can bind to activated T cells expressing the 4-1BB molecule effectively and are similar to human antibodies structurally and to pharmaceutical compositions comprising said humanized monoclonal antibodies. The immune system has tremendous diversity and because the repertoire of specificities expressed by the Band T-cell populations is generated randomly, it is bound to include many which are specific for self components. Thus, the body must establish self-tolerance mechanisms to distinguish between self and non-self determinants so as to avoid autoreactivity. However, all mechanisms have a risk of breakdown. The self-recognition mechanisms are no exception, and a number of diseases have been identified in which there is autoimmunity due to copious production of autoantibodies and autoreactive T cells. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Infant formula with free amino acids and nucleotides Inventor(s): Gohman, Sharon; (New Brighton, MN), Lowry, Carol Jo; (Minneapolis, MN) Correspondence: Thomas Hoxie; Novartis, Patent And Trademark Department; One Health Plaza 430/2; East Hanover; NJ; 07936-1080; US Patent Application Number: 20030054083 Date filed: October 7, 2002 Abstract: A fat-rich powder provides the complete nutritional needs of an at-risk infant no more than one year old, who has acquired a milk allergy, such as cow's milk allergy ("CMA"), and/or an allergy to protein in "soy milk", as well as digestive or absorption problems resulting in a damaged gut. Because such an infant must derive all its protein from amino acids it is not fed any ingredient derived from mammalian milk, but a combination of amino acids with nucleotides in specified amounts along with free Lglutamine, maintaining specified ratios of their relative amounts, which ratios in the ranges stated are found to be beneficial for healing of the infant's damaged gut, and for promoting cell division to assure its normal growth. A typical feeding of 32.6 gm of the powder delivers 160 cals; the powder, including triglycerides of relatively long chain fatty acids which contribute about 50% of the total caloric content of the powder, is nevertheless solubilized when the powder is manually shaken at 35.degree. C. in a bottle containing 240 ml (8 fl oz) of water. Excerpt(s): This invention relates to a non-milk based hypoallergenic infant-formula for "at-risk" infants no more than one year old, who have a documented milk allergy, such as cow's milk allergy ("CMA"), and/or an allergy to protein in "soy milk". By "non-milk based" is meant that no ingredient of the formula is derived from mammalian milk. Because typically, such infants have acquired digestive or absorption problems, the only source of protein in the formula is to be from free amino acids, and the formula is to be storable in powder form but have specified deliverability. By "specified deliverability" is meant that the powder is solubilized in an essentially homogeneous liquid form within less than 30 sees when a unit dosage amount of 32.6 gm of the powder is manually shaken with water at 35.degree. C. in a bottle containing 240 ml (8 fl oz) of water. By "solubilized" is meant that the powder is either soluble in water or forms an emulsion in water forming a liquid having physical characteristics analogous to those of human milk. Still more particularly, the novel formula of the invention does not otherwise mimic human milk in that nutrient powder contains no intact or antigenic proteins; when the powder is solubilized as a ready-to-feed liquid, it is required to have a viscosity less than 10 cp at 25.degree. C. to allow flow through a tube if the formula is delivered enterally rather than taken orally. By "intact protein" is meant a tripeptide or larger molecule having a molecular weight greater than about 500 Daltons; protein hydrolysates of whey or casein contain a major proportion by weight of tripeptides or larger molecules. Hereafter the term "enterally" specifically refers to feeding through a tube such as is typically inserted into the stomach of an infant who cannot easily be fed orally; and the term "at-risk infant" is used to specify one which is no more than one year old. The age limit is critical because a child more than one year old is not seriously "at-risk" since a one-year old is typically fed other food along with formula, and is relatively tolerant to an unbalanced formula for long enough a time to allow a competent nutritionist to alleviate the effects of the misdirected or misapplied diet. A typical infant, not a prematurely born infant, who is to be fed the novel formula weighs in the range from about 2.3 kg (5 lb) to 5.5 kg (12 lb) at birth, and weighs in the range from about 4.5 kg (10 lb) to 11.5 kg (25 lb) after one year. The problem is to provide a storable powder formula which (i) provides the entire nutrition requirement of an at-
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risk infant needing an energy content in the range from about 200-250 Kcal/g nitrogen, without including any intact protein, (ii) is "gut-healing", that is, effective to heal damage already inflicted on the infant's digestive system, and (iii) yet meets the deliverability requirements specified. The problem is solved with a formula having a tailored distribution of amino acids and nucleotides which in combination with a source of unsaturated fats and relatively short chain carbohydrates and other ingredients, provide all the vitamin and mineral needs of the infant, yet prevent GI problems. A nucleotide consists of a nucleoside combined with phosphoric acid; a nucleoside is a compound made of a sugar and a purine or pyrimidine base, especially one obtained by hydrolysis of a nucleic acid, such as adenosine. The term "nucleotide" is used herein as an equivalent of "nucleoside" in that the form in which the compound is present is not critical so long as the specified number of "nucleotide equivalents" are used. A "nucleotide equivalent" refers to the nucleotide content present in any one or more of the following forms: ribo-nucleosides, ribo-nucleotides, RNA, phosphate esters and d-ribose adducts of one with another; the various forms of nucleotides are determined, calculated and expressed as the monophosphate esters. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Maize cytoplasmic glutamine synthetase promoter compositions and methods for use thereof Inventor(s): Hinchey, Brendan; (Mystic, CT), Song, Hee-Sook; (Raleigh, NC) Correspondence: Fulbright & Jaworski L.L.P.; A Registered Limited Liability Partnership; Suite 2400; 600 Congress Avenue; Austin; TX; 78701; US Patent Application Number: 20030140364 Date filed: November 20, 2001 Abstract: The current invention provides the promoter of the Zea mays nuclear gene encoding glutamine synthetase. Compositions comprising this sequence are described, as are plants transformed with such compositions. Further provided are methods for the expression of transgenes in plants comprising the use of these sequences. The methods of the invention include the direct creation of transgenic plants with the cytoplasmic glutamine synthetase promoter by genetic transformation, as well as by plant breeding methods. The sequences of the invention represent a valuable new tool for the creation of transgenic plants, preferably having one or more added beneficial characteristics. Excerpt(s): The present invention relates generally to transgenic plants. More specifically, it relates to methods and compositions for transgene expression using a promoter naturally associated with a Zea mays nuclear gene encoding a cytoplasmic glutamine synthase. An important aspect in the production of genetically engineered crops is obtaining sufficient levels of transgene expression in the appropriate plant tissues, especially tissues that are involved in reproductive functions. In this respect, the selection of promoters for directing expression of a given transgene is crucial. Promoters which are useful for plant transgene expression include those that are inducible, viral, synthetic, constitutive as described (Paszkowski et al., 1984; Odell et al., 1985), temporally regulated, spatially regulated, and spatio-temporally regulated (Chau et al., 1989). A number of plant promoters have been described with various expression characteristics. Examples of some constitutive promoters which have been described include the rice actin 1 (Wang et al., 1992; U.S. Pat. No. 5,641,876), CaMV 35S (Odell et al., 1985), CaMV 19S (Lawton et al., 1987), Ti plasmid nopaline synthase (nos, Ebert et
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al., 1987), alcohol dehydrogenase (Adh, Walker et al., 1987), and sucrose synthase (Yang and Russell, 1990). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Medicament for the treatment of diseases caused by parasitic protozoa Inventor(s): Hofer, Anders; (Umea, SE), Thelander, Lars; (Obbola, SE) Correspondence: Burns Doane Swecker & Mathis L L P; Post Office Box 1404; Alexandria; VA; 22313-1404; US Patent Application Number: 20030109505 Date filed: October 28, 2002 Abstract: The present invention relates to the use of an inhibitor of CTP synthetase, such as a glutamine analogue, and a substance capable of suppressing toxic effects thereof in vivo, in the manufacture of a medicament for the treatment of a disease caused by a parasitic protozoa. More specifically, said substance capable of suppressing toxic effects may be a nucleobase, such as a purine base or a nucleoside, while the glutamine analogue advantageously is 6-diazo-5-oxo-L-norleucine (DON). The invention also relates to a pharmaceutical composition as such for the treatment and/or prevention of a disease caused by a parasitic protozoa, wherein the disease is selected from the group consisting of malaria, leishmaniasis and trypanosomiasis, e.g. American trypanosomiasis (Chaga's disease), or African trypanosomiasis (African sleeping sickness). Excerpt(s): The present invention relates to the manufacture of a medicament for the treatment of a disease caused by a parasitic protozoa and to a pharmaceutical composition as such. Like virus, bacteria, fungi and algae, protozoa is distinct from higher organisms in that they lack the specialized organization of the cells of higher order living systems. Protozoa, which occur in the kingdom Protista, is a microbial species sometimes denoted a predator, since it derives its nutrition from ingestion of bacteria. Many widespread diseases are caused by protozoan pathogens, such as malaria, leishmaniasis and trypanosomiasis. The last mentioned is caused by infections with species of the protozoan genus Trypanosoma. American trypanosomiasis, or Chaga's disease, is caused by T. cruzi, which is usually transmitted to humans by infected triatomid bugs, while African trypanosomiasis, or African sleeping sickness, is caused by infections of Trypanosoma brucei rhodiense and T. b. gambiense. More specifically, African sleeping sickness (for a review see Brun, R. (1999) Karger-Gazette 63, 5-7) is a devastating disease that has got its name from the comatose condition at the final stage of the disease. Without treatment, the patient dies within a couple of months to several years after infection. The severe comatose condition described occurs when these parasites from mainly being circulating in the bloodstream also invade the central nervous system. T. brucei is spread between its mammalian hosts by tsetse flies. The parasite goes through many different life cycle stages in the mammalian host as well as in the fly (Vickerman, 1985). When the trypanosomes enter the mammalian host through a tsetse bite, they start to proliferate as long slender bloodstream forms. While the disease progresses, more and more trypanosomes are converted to short stumpy forms that are unable to proliferate but in contrast to the long slender forms can be transmitted to a new tsetse fly. In the fly, the trypanosomes go through some further developmental stages before they are passed on to a new mammalian host. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for identifying JNK and MLK inhibitors for treatment of neurological conditions Inventor(s): Liu, Ya Fang; (Boston, MA) Correspondence: Ropes & Gray Llp; One International Place; Boston; MA; 02110-2624; US Patent Application Number: 20030148395 Date filed: February 5, 2003 Abstract: The present invention describes methods for identifying compounds that inhibit JNK and MLK kinase activity as drugs for treating a mammal susceptible to or having a neurological condition. This invention also discloses methods for preventing neuronal cell death and treating neurological conditions that involve neuronal cell death, particularly neurodegenerative diseases characterized by glutamine or kainate mediated toxicity, such as Huntington's disease and Alzheimer's disease. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/085,439, filed May 14, 1998, the entire teachings of which are incorporated herein by reference. Excitotoxicity is related to excessive activation of glutamate receptors which results in neuronal cell death. The physiological function of glutamate receptors is the mediation of ligand-gated cation channels with the concomitant influx of calcium, sodium and potassium through this receptor-gated channel. The influx of these cations is essential for maintaining membrane potentials and the plasticity of neurons which in itself plays a pivotal role in cognitive function of the central nervous system. Li, H. B., et al., Behav. Brain Res., 83:225-228 (1997); Roesler, R., et al., Neurology, 50:1195 (1998); Wheal, H. V., et al., Prog. Neurobiol., 55:611-640 (1998); Wangen, K., et al., Brain Res., 99:126-130 (1997). Excitotoxicity plays an important role in neuronal cell death following acute insults such as hypoxia, ischemia, stroke and trauma, and it also plays a significant role in neuronal loss in AIDS dementia, epilepsy, focal ischemia. Coyle, J. T. & Puttfarken, P., Science, 262:689-695 (1993). Neurodegenerative disorders, such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), are characterized by the progressive loss of a specific population of neurons in the central nervous system. Growing evidence suggests that glutamate-mediated excitotoxicity may be a common pathway which contributes to neuronal cell death in a wide range of neurological disorders. Coyle, J. T. & Puttfarken, P., Science, 262:689-695 (1993). The molecular mechanisms of excitotoxicity-mediated neuronal cell death remains obscure. Over-production of free radicals that lead to impairment of mitochondrial function is the most widely held hypothesis. Beal, M. F., et al., Ann. Neurol., 38:357-366 (1995); Coyle, J. T. & Puttfarken, P., Science, 262:689-695 (1993). However, it is unclear whether the increase of free radicals is the precursor that initiates neuronal degeneration or, rather, a subsequent consequence of neuronal degeneration. Interestingly, administration of antioxidants has little neuroprotective effect in patients suffering from various neurodegenerative diseases. Shults, C. W., et al., Neurology, 50:793-795 (1998). Thus, some other mechanism(s) must exist for excitotoxicity-induced neuronal cell death. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for preventing decrease of breast milk amount in mammals Inventor(s): Kobayashi, Hisamine; (Kanagawa, JP), Nishimura, Naoki; (Kanagawa, JP), Shibahara, Susumu; (Kanagawa, JP), Shinzato, Izuru; (Kanagawa, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20040010042 Date filed: June 5, 2003 Abstract: A method for preventing decrease of a breast milk amount in a mammal, which comprises administering glutamine to the mammal. Excerpt(s): The present invention relates to a method for preventing decrease of a breast milk amount in mammals. Mammals secrete breast milk after parturition. When mammals are under poor physical conditions, suffer from diseases or are under poor nutritional conditions, their milk secretion is decreased and subsequently growth or nutritional status of their babies is deteriorated. In the case of economic animals, such as a cow or a goat, of which milk and processed products thereof are edible for human beings, the decrease of the milk amount leads to a great economic loss and serious problems take place for dairy farmers. In particular, when high-producing daily cows suffer from metabolic diseases during periparturient period, e.g., retained placenta, milk fever, ketosis, displaced abomasum and mastitis, or when they are under sub-clinical disease conditions even if they are not actually showing symptoms of these diseases, great problems are caused because their milk amounts are decreased and it takes long to be recovered therefrom. Methods for preventing decrease of a breast milk amount in economic animals include a method such as feeding a large amount of ingredients having a high energy value such as sugar and starch to mammals to thereby increase the intake of energy in the mammals, and supplying a feed to mammals containing a lot of protein such as fish meal and blood meal. However, these methods are all inexpensive but are not so effective. In the case of ketosis caused in daily cows under poor nutritional conditions, intravenous injection of saccharides such as glucose is known as an ordinary treatment method. However, the effect is temporarily, and the amount of milk which has been once decreased cannot be completely restored. An objective of the present invention is to provide a novel method which is inexpensive and safe for preventing decrease of an breast milk amount in mammals. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Method for producing a gluten-free peptide preparation and preparation thus obtained Inventor(s): Hunter, Edward Allan; (Hancock, NY), Merrill, Debra Ann; (Downsville, NY) Correspondence: Webb Ziesenheim Logsdon; Orkin & Hanson, P.C.; 700 Koppers Building; 436 Seventh Avenue; Pittsburgh; PA; 15219-1818; US Patent Application Number: 20020165125 Date filed: January 9, 2002 Abstract: The invention relates to a method for producing a glutamine-rich gluten-free peptide preparation from gluten protein, comprising the steps of enzymatically hydrolysing wheat gluten using one or sore proteases to obtain a hydrolysate; acidifying
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the hydrolysate to a pH between 4 and 5; and filtering the hydrolysate to obtain the glutamine-rich gluten-free peptide preparation as the filtrate. The protease is preferably a neutral or basic protease and the optimum pH is from, 4.5 to 4.7. Excerpt(s): The present invention relates to a method for producing a peptide preparation that is both glutamine-rich and gluten-free and to the preparation thus obtained. The invention also relates to the use of the preparation in various products and to the products containing the preparation. Gluten is a combination of proteins found in the endosperm of various grains, such as wheat, barley and rye, oats and other gluten-containing wheat variants, such as triticale, spelt and kamut. In wheat, gluten accounts for 90% of the protein and sakes up almost 15% of the total weight of a grain. It is thus an important source of protein. However, gluten is the cause of a genetic disorder known as coeliac disease or gluten intolerance. Symptoms of coeliac disease can range from the classic features, such as diarrhea, weight loss, and malnutrition, to latent symptoms such as isolated nutrient deficiencies. The disease mostly affects people of European descent, and occurs more rarely in black and Asian populations. Those affected suffer damage to the villi (shortening and villous flattening) in the lamina propria and crypt regions of their intestines when they eat specific food-grain antigens (toxic amino acid sequences) that are found in wheat, rye, and barley, oats and other gluten-containing wheat variants, such as triticale, spelt and kamut. The gluten found in rice and corn do not cause the intolerance. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for producing L-glutamine by fermentation and L-glutamine producing bacterium Inventor(s): Izui, Hiroshi; (Kawasaki-shi, JP), Kawashima, Hiroki; (Kawasaki-shi, JP), Kurahashi, Osamu; (Kawasaki-shi, JP), Moriguchi, Kayo; (Kawasaki-shi, JP), Nakamatsu, Tsuyoshi; (Tokyo, JP), Nakamura, Jun; (Kawasaki-shi, JP) Correspondence: Oblon Spivak Mcclelland Maier & Neustadt PC; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030003550 Date filed: February 5, 2002 Abstract: L-Glutamine is produced by culturing a coryneform bacterium which has Lglutamine producing ability and has been modified so that its intracellular glutamine synthetase activity should be enhanced, preferably which has been further modified so that its intracellular glutamate dehydrogenase activity should be enhanced, in a medium to produce and accumulate L-glutamine in the medium and collecting the L-glutamine. Excerpt(s): The present invention relates to an L-glutamine producing bacterium belonging to coryneform bacteria and a method for producing L-glutamine. LGlutamine is an industrially useful amino acid as an ingredient of seasonings, liver function promoting agents, amino acid transfusions, comprehensive amino acid preparations and so forth. In order to produce L-amino acids by fermentation, methods for improving microorganisms by breeding have been used abundantly. That is, since production ability of wild strains per se for L-amino acid production is extremely low in many cases, there have been known methods of imparting auxotrophy or analogue resistance by mutation or imparting mutation for metabolic regulation and methods utilizing a combination of these. Although L-glutamine can be obtained with an appropriate yield by the aforementioned methods, it is indispensable to further improve
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the fermentation yield in order to industrially produce L-glutamine at a low cost. Further, the L-glutamine fermentation also suffers from the problem of by-production of L-glutamic acid. A method for solving this problem is proposed in, for example, Japanese Patent Laid-open Publication (Kokai) No. 3-232497. Although the production of L-glutamic acid can be suppressed to a certain extent by this method, there is still byproduction of L-glutamic acid and the yield of L-glutamine is insufficient. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of reducing body weight and/or body fat with L-glutamine compounds Inventor(s): Ueda, Takeo; (Kawasaki-shi, JP) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20040043055 Date filed: August 28, 2002 Abstract: A method and compositions for reducing body weight, body fat, or both. Excerpt(s): The present invention relates to methods and compositions for reducing body weight, body fat, or both. There remains a need for compositions and methods for reducing body weight, body fat, or both. Compositions containing L-glutamine have been used for this purpose. For example, it has been reported that addition of 3.6% of Lglutamine to the basal diet of mice inhibited body weight gain (Opara et al., J. Nutr. 126:273 (1996)). In addition, WO 95/11019 describes a beverage composition which contains L-glutamine in an amount from 1 to 4 g per 473 milliliters of the beverage which is reported to enhance physical performance and reduce body fat by inducing a growth hormone response. However, there remains a need for improved compositions for reducing body weight and/or body fat. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and compositions for providing glutamine Inventor(s): Baxter, Jeffrey H.; (Galena, OH) Correspondence: Ross Products Division OF Abbott Laboratories; Department 108140ds/1; 625 Cleveland Avenue; Columbus; OH; 43215-1724; US Patent Application Number: 20030099722 Date filed: October 9, 2001 Abstract: Methods and compositions for providing glutamine supplementation to a human by orally administering an effective amount of N-acetyl-L-glutamine or a nutritionally acceptable salt thereof. The N-acetyl L-glutamine or a nutritionally acceptable salt thereof can be incorporated into any liquid composition that is suitable for human consumption. Examples of suitable compositions include aqueous solutions such as for use as oral rehydration solutions and liquid nutritional formulas (including enteral formulas, oral formulas, formulas for adults, formulas for children and formulas for infants). The quantity of N-acetyl-L-glutamine or nutritionally acceptable salt thereof can vary widely but typically, these compositions will contain sufficient N-acetyl-Lglutamine or a nutritionally acceptable salt thereof to provide at least 140 mg of total glutamine per kg of body weight per day.
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Excerpt(s): The invention relates to methods for providing glutamine supplementation via the oral administration of an effective amount of N-acetyl-L-glutamine, or a nutritionally acceptable salt thereof. Glutamine is the most abundant amino acid in the human body. It comprises more than 60% of the free amino acids in skeletal muscle and more than 20% of the total circulating amino acids. Glutamine is involved in many body functions, including gluconeogenesis, nucleotide synthesis, acid-base balance and other critical metabolic processes. Studies have indicated that glutamine is an important metabolic substrate used by rapidly replicating cells, particularly gastrointestinal tract and mucosal cells. Glutamine can be efficiently absorbed in the human jejunum (part of the small intestine) in vivo. Glutamine is not considered an essential amino acid because it can be synthesized by virtually all tissues of the body. It is believed to be produced in sufficient quantities to adequately supply body needs (i.e., glutamine-consuming tissues) when the body is in a normal physiologic condition. However, numerous studies have shown that during abnormal physiologic conditions (i.e., disease and metabolic stress), glutamine production can become insufficient to meet the body's needs. Thus, glutamine may be more accurately considered a conditionally essential amino acid. For example, several studies have classified glutamine as such in cases of gut trauma. Souba, W. W.; Smith, R. J.; and Wilmore, D. J.: Glutamine Metabolism by the Intestinal Tract. JPEN 9(5): 608-617 (1985); Furst, P.; Albers, S and Stehle, P.: Evidence for a nutritional need for glutamine in catabolic patients. Kidney Intl. 36 (Suppl. 27): S-287-S-292 (1989); Klimberg, V.S., et al.: Oral glutamine accelerates healing of the small intestine and improves outcome after whole abdominal radiation. Glutamine has also been suggested as a primary energy source for cultured HeLa cells. Reitzer, L. J.; Wice, B. M.; and Kennell, D.: Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J. Biol. Chem. 254(8): 2669-2676 (1979). And, it has been suggested that glutamine may be preferentially utilized by tumor cells, resulting in progressive glutamine depletion in cancer patients. Souba, W. W.: Glutamine and Cancer. Ann. Surg. 218(6): 715-728 (1993). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods and systems for hydrazine remediation Inventor(s): De Baca, Jose C; (Las Vegas, NM), Helvenston, Merritt C.; (Las Vegas, NM), Juarez, John J.; (Las Vegas, NM), Martinez, Rodolfo A.; (Santa Fe, NM) Correspondence: Kermit D. Lopez/luis M. Ortiz; Ortiz & Lopez, Pllc; Patent Attorneys; P.O. Box 4484; Albuquerque; NM; 87196-4484; US Patent Application Number: 20040024251 Date filed: August 1, 2002 Abstract: Methods of and systems for remediating hydrazine spills, solutions and hydrazine-contaminated objects including areas thereof. Initially, an aqueous solution comprising a dicarbonyl-compound can be prepared. The aqueous solution can then be provided for application to an object contaminated with a hydrazine group compound. The hydrazine group compounds are converted to a stable organic compound as a result of a reaction of the dicarbonyl-compound and hydrazine group compound. Conversion assists in the remediation of the hydrazine group compound from the object. The stable organic compound produced as a result of the reaction between the dicarbonylcompound and hydrazine group compound can then be treated with a metal catalyst and hydrogen to produce glutamine or a derivative thereof. Both the stable organic
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compound and glutamine can undergo microbiological degradation without further remedial intervention. Excerpt(s): The present invention is generally related to decontamination and remediation methods and systems. The present invention is also related to hydrazine (Hz) and hydrazine-based compounds, such as monomethylhydrazine (MMH) or 1,1dimethylhydrazine (UDMH). The present invention additionally relates to methods and systems for remediating hydrazine from hydrazine-contaminated objects, including hydrazine contaminated areas thereof. The present invention is also related to dicarbonyl compounds, including dialdehydes, diketones, aldehyde-ketones, aldehydeacids, aldehyde-esters, keto-acids and keto-esters. The present invention is specifically related to the involvement of the following compounds in remediation of hydrazine: 2ketoglutaric acid (2KG), 6-oxo-1,4,5,6-tetrahydro-pyridazine-3-carbonic acid (PCA), and glutamine. An environmentally conscious remediation process for the emergency treatment/disposal of hydrazine fuels spills is needed. The highly toxic hydrazine family of fuels is utilized as rocket propellants in virtually all U.S. space programs including both launch vehicles and satellite propulsion systems. Since large volumes of these fuels are annually shipped all over the United States, accidental major spills of these propellants could potentially occur near populated communities during transport over the nation's highways. In addition, smaller spills could also occur during launch operations and storage at the user facilities. An inadvertent release of hydrazine to the environment can be extremely hazardous due to the mutagenic nature of such chemical compounds, which can induce tumor growth in human beings years following even a low level exposure. Hydrazine compounds are classified as suspected human carcinogens and their permissible levels of exposure have been reduced to 10 parts per billion (ppb). A hydrazine spill remediation process, to be developed, should not only destroy the propellant fuel but also should not generate other hazardous materials. An in-situ processing method involving direct application of the treatment reagent or process to the spill is preferred. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for diagnosing activated protein C resistance associated with a factor V genetic mutation and compositions thereof Inventor(s): Greengard, Judith; (San Diego, CA), Griffin, John H.; (Del Mar, CA) Correspondence: The Scripps Research Institute; Office OF Patent Counsel, Tpc-8; 10550 North Torrey Pines Road; LA Jolla; CA; 92037; US Patent Application Number: 20030008307 Date filed: April 2, 2002 Abstract: A method for identifying a Factor V gene mutation resulting in activated protein C resistance comprising detecting in a nucleic acid sample isolated from a human the presence of a genetic mutation characterized as a change from a guanine nucleotide to an adenine nucleotide at nucleotide position 205 in exon 10 of the Factor V gene that is associated with replacement of arginine 506 by glutamine, thereby identifying said mutation. Excerpt(s): The present invention relates to a method for detecting a coagulation Factor V allele resulting in activated Protein C (APC) resistance in a human. This allele is a point mutation characterized as a change from a guanine nucleotide to an adenine nucleotide at nucleotide position 205 in exon 10 of the normal Factor V gene. The exon
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10 point mutation corresponds to nucleotide position 1691 of the Factor V cDNA sequence. Blood coagulation reactions and thrombosis play major roles in cardiovascular diseases. Risk factors for these diseases include both inherited and acquired risk factors. Studies of hereditary thrombophilia, defined as an increased tendency towards venous thrombotic disease in relatively young adults, provide insights into factors that regulate thrombosis. Hereditary thrombophilia has been associated with molecular defects of antithrombotic factors, including antithrombin III, protein C and protein S. However, molecular defects which involve these factors have been identifiable in only 10-15% of thrombophilic patients. Therefore, a molecular defect has not been identified in the vast majority of these patients (Gladson et al, Thromb. Haemost. 59:18, 1988; Allaart et al, Lancet 341:134, 1993; Horellou et al, Br. Med. J. 289:1285, 1984; Pabinger et al, Thromb. Res. Suppl. VI 136a, 1986; Malm et al, Thromb. Haemost. 68:7, 1992; Ben-Tal et al, Thromb. Haemost. 61:50, 1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Microorganisms and processes for producing L-glutamine Inventor(s): Jeong, Sang-Cheol; (Kyunggi-do, KR), Kim, Cheon-Ju; (Kyunggi-do, KR), Lee, Dong-Woo; (Kyunggi-do, KR), Lee, Keun-Chul; (Kyunggi-do, KR), Park, Sung-Sik; (Seoul, KR), Suh, Seung-Hyun; (Kyunggi-do, KR) Correspondence: Baker & Botts; 30 Rockefeller Plaza; New York; NY; 10112 Patent Application Number: 20030096380 Date filed: July 17, 2002 Abstract: The present invention provides novel microorganisms, Brevibacterium lactofermentum CJJA21 (Accession No. KCCM-10222), which is resistant to sodium azide, and Brevibacterium lactofermentum CJJA22 (Accession No. KCCM-10223), which is resistant to.alpha.-aminobutyric acid. These microorganisms are capable of producing L-glutamine in a higher yield than the known strains. The present invention further provides processes for producing L-glutamine using the microorganisms of the invention. Excerpt(s): This application is a continuation application of International Application Serial No. PCT/KR01/01952, filed Nov. 15, 2001 and published as WO 02/40643, which claims priority to Korean Application Serial No. 2000/68284 and Korean Application Serial No. 2000/68285, both filed Nov. 17, 2000. Said applications are included herein in their entirety by reference. L-glutamine is an amino acid widely used as medicines such as therapeutic agents of gastroenterologic disorders, potentiators of liver and brain functions, immuno-enhancement agents, and therapeutic agents of gastric ulcer and alcoholism, etc., cosmetics such as moisturizers, etc., and health foods such as sports nutrients and nutrients for patients, etc. According to the prior art, L-glutamine was obtained from sulfaguanidine-resistant strains (Japanese Patent, Laid-Open No. Sho5317675), azaserine-resistant strains (Japanese Patent Laid-Open No. Sho55-148094) penicillin-sensitive strains (Japanese Patent Laid-Open No. Hei04-088994), tyrosineglutamic acid (tyr-glu)-resistant strains (Japanese Patent Laid-Open No. Hei02-186994) and the like. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Molecule of pharmaceutical interest comprising at its n-terminal a glutamic acid or a glutamine in the form of a physiologically acceptable strong acid Inventor(s): Alain, Beck; (Saleve, FR), Klinguer-Hamour, Christine; (Groisy, FR), Liliane, Goetsch; (Ayze, FR), Nathalie, Corvaia; (Genevois, FR) Correspondence: The Firm OF Hueschen And Sage; 500 Columbia Plaza; 350 East Michigan Avenue; Kalamazoo; MI; 49007; US Patent Application Number: 20030175285 Date filed: September 19, 2002 Abstract: The invention concerns a molecule of pharmaceutical interest, preferably a major histocompatibility complex (MHC) ligand, comprising a glutamic acid or a glutamine at its N-terminal, in the form of a physiologically acceptable addition salt, and a vaccine comprising such a ligand. Excerpt(s): The subject of the present invention is a molecule of pharmaceutical interest, preferably a ligand for the Major Histocompatibility Complex (MHC), containing a glutamic acid or a glutamine at its N-terminal end, which exists in the form of a physiologically acceptable addition salt with a strong acid, and a vaccine comprising such a ligand. Vaccination is an effective means for preventing or reducing viral or bacterial infections. The vaccine antigens when administered alone to the host are often not sufficiently immunogenic to induce an immune response, and should therefore be combined with an adjuvant or coupled to a carrier protein in order to elicit (or increase) their immunogenicity. Under these conditions, only a humoral type immune response may be induced. However, in the context of an antiviral therapy, the generation of cytotoxic T lymphocytes (CTL) capable of recognizing and destroying the virus is of primary importance (Bachmann et al., Eur. J. Immunol., 1994, 24, 2228-2236; Borrow P., J. Virol. Hepat., 1997, 4, 16-24), as demonstrated by numerous studies showing in vivo the protective role of the responses directed against the viral epitopes (Arvin A. M., J. Inf. Dis., 1992, 166, pp. 35-41; Koszinowski et al., Immunol. Lett., 1987, 16, 185-192). The importance of the CTL and helper T responses has also been indeed described for vaccines against parasites such as Plasmodium falciparum, the agent responsible for Malaria (Le et al., Vaccine, 1998, 16, 305-312). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Mutated bmp1b receptor as regulator of ovulation rate Inventor(s): Wilson, Theresa Mary; (Dunedin, NZ), Wu, Xi-Yang; (Sydney, AU) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20030153035 Date filed: December 23, 2002 Abstract: The present invention is related to an isolated mutated nucleic acid molecule encoding the BMP1B receptor polypeptide. This molecule has a sequence which differs from that of the wild type BMP1B receptor polypeptide in that the codon encoding amino-acid residue 249 encodes arginine rather than glutamine, is able to hybridize under stringent conditions to the molecule above, is a variant of the molecule above, is a complement of any of the molecules above, or is an anti-sense sequence corresponding to any of the sequences in the molecules described above.
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Excerpt(s): The present invention concerns variation of ovulation rate in animals. In one aspect a mutation in a gene is involved in increasing the ovulation rate in heterozygous and homozygous female vertebrates. The mutated gene sequence can be used in a test to identify heterozygous or homozygous female and male vertebrates carrying said mutated gene. In a further aspect the invention relates to identification of the protein responsible for determining the ovulation rate in vertebrates. In yet a further aspect the invention concerns modulation of the activity of this protein to control the ovulation rate in female vertebrates. It will be clearly understood that, although a number of prior art publications are referred to herein, this reference does not constitute an admission that any of these documents form part of the common general knowledge in the art, in New Zealand or in any other country. A Booroola ram is currently of added value if the carrier status of the ram is known. Rams carrying the Booroola gene have been exported to many countries, including France, Britain, South Africa, Poland, Chile, Israel, Netherlands and the USA, with the intention of introgressing the high lambing found in the Booroola into their own flocks. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nematode GS-like sequences Inventor(s): Kloek, Andrew P.; (St. Louis, MO), McLaird, Merry B.; (Brentwood, MO), Salmon, Brandy; (Durham, NC), Williams, Deryck J.; (St. Louis, MO) Correspondence: Fish & Richardson PC; 225 Franklin ST; Boston; MA; 02110; US Patent Application Number: 20030235898 Date filed: May 27, 2003 Abstract: Disclosed is a nucleic acid molecule from nematodes encoding for glutamine synthetase (GS) polypeptides. The GS-like polypeptide sequence is also provided, as are vectors, host cells, and recombinant methods for production of GS-like nucleotides and polypeptides. The invention further relates to screening methods for identifying inhibitors and/or activators, as well as methods for antibody production. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 10/098,602, filed Mar. 15, 2002, which claims priority from U.S. provisional application serial No. 60/276,621, filed Mar. 16, 2001. Nematodes (derived from the Greek word for thread) are active, flexible, elongate, organisms that live on moist surfaces or in liquid environments, including films of water within soil and moist tissues within other organisms. While only 20,000 species of nematode have been identified, it is estimated that 40,000 to 10 million actually exist. Some species of nematodes have evolved to be very successful parasites of both plants and animals and are responsible for significant economic losses in agriculture and livestock and for morbidity and mortality in humans (Whitehead (1998) Plant Nematode Control. CAB International, New York). Nematode parasites of plants can inhabit all parts of plants, including roots, developing flower buds, leaves, and stems. Plant parasites are classified on the basis of their feeding habits into the broad categories: migratory ectoparasites, migratory endoparasites, and sedentary endoparasites. Sedentary endoparasites, which include the root knot nematodes (Meloidogyne) and cyst nematodes (Globodera and Heterodera) induce feeding sites and establish long-term infections within roots that are often very damaging to crops (Whitehead, supra). It is estimated that parasitic nematodes cost the horticulture and agriculture industries in excess of $78 billion worldwide a year, based on an estimated average 12% annual loss spread across all major crops. For example, it is estimated that nematodes cause soybean losses of approximately $3.2 billion annually
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worldwide (Barker et al. (1994) Plant and Soil Nematodes: Societal Impact and Focus for the Future. The Committee on National Needs and Priorities in Nematology. Cooperative State Research Service, US Department of Agriculture and Society of Nematologists). Several factors make the need for safe and effective nematode controls urgent. Continuing population growth, famines, and environmental degradation have heightened concern for the sustainability of agriculture, and new government regulations may prevent or severely restrict the use of many available agricultural anthelmintic agents. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
New mutant glutamine synthetase and method for producing amino acids Inventor(s): Chudakova, Daria Aleksandrovna; (Moscow, RU), Filippov, Dmitriy Vladimirovich; (Moscow, RU), Gusyatiner, Mikhail Markovich; (Moscow, RU), Ivanovskaya, Lirina Valerievna; (Moscow, RU), Leonova, Tatyana Viktorovna; (Moscow, RU), Mukhanova, Ekaterina Igorevna; (Moscow, RU), Rostova, Yulia Georgievna; (Moscow, RU) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; Fourth Floor; 1755 Jefferson Davis Highway; Arlington; VA; 22202; US Patent Application Number: 20030148474 Date filed: November 20, 2002 Abstract: Amino acids, such as L-glutamine, L-arginine, L-tryptophan, L-histidine and L-glutamate are produced using a bacterium belonging to the genus Escherichia harboring a mutant glutamine synthetase in which the tyrosine amino acid residue corresponding to position 397 in a wild type glutamine synthetase is replaced with any of amino acid residues, preferably with phenylalanine. Excerpt(s): The present invention relates to microbiological industry, specifically to a method for producing amino acids. More specifically, the present invention concerns an use of a new enzyme involved in glutamine biosynthesis and nitrogen assimilation pathways of E. coli strains producing amino acids, such as glutamine and arginine. More specifically, the present invention concerns a new mutant glutamine synthetase and a method for producing amino acids, such as glutamine, arginine, tryptophan, histidine and glutamate, using E. coli strains harboring the enzyme. Glutamine synthetase (GS) has two functions in E. coli: the formation of glutamine and assimilation of ammonia when the availability of ammonia is restricted. Glutamine donates nitrogen for the synthesis of purines and pyrimidines, and for some amino acids, such as arginine, tryptophan, asparagine, histidine and glutamate. In case of arginine biosynthesis, glutamine plays significant role, since glutamine is used as the only physiological amino group donor for synthesis of carbamoylphosphate, which is a common precursor for arginine and the pyrimidines. In case of tryptophan formation, glutamine is utilized in the first reaction of tryptophan biosynthetic pathway, which involves the conversion of chorismate and glutamine to anthranilate, glutamate, and pyruvate. The glutamine-dependent asparagine synthetase uses glutamine together with asparatate and ATP in the major pathway for asparagine biosynthesis. The nitrogen 3 of imidazole ring of histidine originates from glutamine. And finally, glutamine is used by glutamate oxoglutarate aminotransferase (GOGAT) in the synthesis of glutamate. Because of the multiple functions and importance of GS in cellular metabolism both its catalytic activities and its synthesis are highly regulated.
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Novel dosage form of L-Methionine S-Sulfoximine Inventor(s): Brusilow, Saul; (Baltimore, MD), Koehler, Raymond C.; (Baltimore, MD), Traystman, Richard J.; (Ruxton, MD) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 1425 K Street, N.W.; Suite 800; Washington; DC; 20005; US Patent Application Number: 20030144357 Date filed: January 31, 2002 Abstract: A novel dosage form of L-Methionine S-Sulfoximine for the treatment of diseases and conditions susceptible to the inhibition of glutamine synthetase is disclosed. The novel dosage form should not exceed 10 mg/kg by body weight over a one week period, and preferably should not exceed 8 mg/kg, and more preferably should not exceed 5 mg/kg, and most preferably should not exceed 2.5 mg/kg. Excerpt(s): The Gersoff reference entitled "The Relative Effect of Methionine Sulfoximine on Different Animal Species" reported the results of experiments involving the intraperitoneally injected methionine sulfoximine (hereinafter "MSO") into rats, the subcutaneous injection of MSO into mongrel puppies, and intraperitoneal injections of MSO into monkeys. The experiments determined the minimum toxic doses of MSO for dogs, rats and monkeys. It was further determined that rats and monkeys are approximately 100 times more resistant to MSO than dogs. It was also discovered that MSO-induced seizures could be suppressed by the administration of methionine. The amount ratio for methionine (which prevents seizures) to MSO (which causes seizures) was determined in monkeys and dogs. As stated above, Gershoff demonstrates species specificity for toxicity and also that dogs are especially vulnerable whereas monkeys (primates are not). It was also shown that monkeys could withstand doses of 50 and 100 mg/kg of mixed isomers of MSO. Gershoff, "The Relative Effect of Methionine Sulfoximine on Different Animal Species," J Nutr 45:451-458 (1951). The Krakoff reference entitled "Effect of Methionine Sulfoximine in Man" involved the administration of MSO to hospitalized patients with far-advanced, nonresectable cancer. The MSO was given in divided doses every 6 or 8 hours. The result of this experiment was no change in hepatic or renal function or in hematological status. Further, no evidence of tumor regression was discovered. It was noted that MSO impacted the central nervous system in the form of hallucinations, disorientation, and marked agitation. The author suggested that the symptoms were related to the size of the daily dose rather than a cumulative dose. In the reported experimentation, each patient was given a laboratory evaluation of their hepatic, renal, and hematologic status before the experimentation began. These evaluations were continued at regular intervals during the course of the experimentation and each subject was watched for evidence of tumor regression, measurable either enterogenographically or by direct observation of tumor masses. No evidence of tumor regression was noted. It was also noted that the abnormal mental state cleared on its own and without the addition of methionine. The reference also disclosed that the most probable reason that convulsions did not occur in the test subjects was that the MSO had been withdrawn before the convulsive state had been reached. It was stated that the precise mechanism by which the methionine analogues produce their toxic effects was not known, but the article disclosed that MSO appears to inhibit the incorporation of other amino acids into protein, and that this inhibition is prevented by glutamine. The article continued to disclose that the synthesis of
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glutamine from glutamate and the transfer of glutamyl groups have been inhibited by MSO. However, the article could not disclose whether MSO's relationship to glutamine is responsible for the neurotoxicity of MSO or for its potentiation of the tumor-inhibitory effects of the glutamine antagonists azaserine and DON. Lastly, it noted that the effects of MSO and ethionine in man are not identical. Krakoff, Effect of Methionine Sulfoximine in Man," J. Pharm. Experimental Ther., 2:599-604 (1961). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel protein tyrosine phosphatase substrate-trapping double mutant and uses thereof Inventor(s): Xie, Laiping; (Bronx, NY), Zhang, Yan-Ling; (Belmont, MA), Zhang, ZhongYin; (Scarsdale, NY) Correspondence: Elie H. Gendloff; Amster, Rothstein & Ebenstein; 90 Park Avenue; New York; NY; 10016; US Patent Application Number: 20030170855 Date filed: January 10, 2003 Abstract: The present invention provides protein tyrosine phosphatases (PTP) in which the invariant aspartate residue and the invariant glutamine residue are each replaced with a replacement amino acid residue, wherein the replacement residues together cause a reduction in catalytic rate (k.sub.cat) of the enzyme and an increase in substratebinding affinity (K.sub.d) of the enzyme. The present invention further provides methods for identifying a substrate of a PTP. Also provided are kits for identifying a substrate of a PTP. Additionally, the present invention provides methods for identifying an agent that alters interaction between a PTP and a substrate of the PTP. The invention also provides methods for reducing the activity of a substrate of a PTP. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/347,413, filed Jan. 11, 2002. Sequencing of the human and other genomes has radically changed the ways in which we identify and characterize genes. Typically, database searches that are based on structural similarities can assign a gene product to an established protein family. Although members of protein families often share a common mechanism of action, the cellular processes in which they are involved can be both highly specialized and fundamentally important. Protein tyrosine phosphatases (PTPs), enzymes which have conserved catalytic domains but are involved in controlling a broad constellation of cellular processes (1-3), provide a striking example of conserved structures associated with functional diversity. The hallmark that defines the PTP superfamily is the active site amino acid sequence (H/V)C(X).sub.5R(S/T), also referred to as the PTP signature motif, within the catalytic domain. To date, analysis of the nearly completed human genome has revealed 112 predicted human PTPs (4). Therefore, it is relatively easy to attribute a general role to a PTP gene product based upon structural homologies. However, determination of the exact physiological function of a PTP requires a tedious and protracted effort. Identification of the cellular substrates of individual PTPs will help to elucidate the biological functions of individual PTPs. A major challenge, though, is the development of technologies for rapid substrate identification that can be applied to the entire PTP family. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Nutritional preparation comprising ribose and medical use thereof Inventor(s): Hageman, Robert Johan Joseph; (Waddinxveen, NL), Smeets, Rudolf Leonardus Lodewijk; (Waddinxveen, NL), Verlaan, George; (Wageningen, NL) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20020183263 Date filed: June 25, 2002 Abstract: Trauma, surgery, inflammation, subfertility, pregnancy, lactation problems, gut disorders, infant nutrition, cancer, arthritis and other joint problems, vascular problems and cardio-or cerebro-vascular problems, ischaemia, aging, impaired immune function, burns, sepsis, malnutrition, problems with liver, pancreas or kidneys, malaria, cystic fibrosis, migraine, neurological problems, respiratory infections, improvement of sports results, muscle soreness, drug intoxication and pain can be treated with a nutritional composition containing effective amounts of ribose and folic acid, optionally combined with other components such as niacin, histidine, glutamine, orotate, vitamin B6 and other components. Excerpt(s): The invention is related to nutritional, pharmaceutical, or dietetic preparations that comprise ribose or folic acid or functional analogs thereof and the use of these compositions in the prevention or treatment of specific diseases that are related to disorders or insufficient of total nucleotide metabolism. Nucleotides are heterocyclic compounds that occur in all mammals. Nucleotides consist of a purine or pyrimidine base, a sugar unit and one to three phosphate groups. The major purine bases that occur in the human body are adenine (6-aminopurine), guanine (2-amino-6-hydroxypurine), hypoxanthine (6-hydroxypurine) and xanthine (2,6-dihydroxypurine); the major pyrimidines are uracil (2,4-dihydroxypyrimidine), cytosine (2,4-dihydroxy-5methylpyrimidine) and thymine (4-amino-2-hydroxypyrimidi- ne). The sugar moiety can be ribose (in ribonucleosides) or 2-deoxyribose. The sugar moiety is connected to the base through a.beta.-N-glycosidic bond at N9 of the base; the phosphate groups are connected to the sugar moiety through the 3' or 5' position. When the phosphate groups are split from nucleotides compounds called nucleosides are formed. For the purpose of this document, total nucleotide metabolism (TNM) is defined as the combination of all biochemical pathways in which nucleotides, their precursors and metabolites are directly involved as main ingredients and that occur in the body of mammals. The pathways include the synthetic routes for purines and pyrimidines, both de novo and salvage pathways, starting from carbamoyl phosphate and 5-phosphoribosyl-1pyrophosphate (PRPP), respectively. They also include the interconversions of the various nucleotides into each other, the phosphorylation and dephosphorylation reactions of respectively nucleosides and nucleotides and the catabolic pathways of nucleotides to the compounds that are cleared from the body. They do not include the further reactions of phosphoric groups thus split off from the phosphorylated nucleotides. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Peptides which stimulate the immune response and tissue regeneration Inventor(s): Achour, Ammar; (Creteil, FR), Barritault, Denis; (Paris, FR), Courty, Jose; (Villecresnes, FR) Correspondence: Schnader Harrison Segal & Lewis Llp; Suite 3600; 1600 Market Street; Philadelphia; PA; 19103; US Patent Application Number: 20030087255 Date filed: April 4, 2002 Abstract: A pharmaceutical composition for stimulating production of cytokines of inflammation including a peptide corresponding to formula (I) below:(A).sub.n-A1-A1A2-A1-A3-A4-A1-(A).sub.min which A is any amino acid, n and m are each whole numbers from 0 to 20 whose sum n+m is between 0 and 20, A1 is a basic amino acid and more particularly lysine (Lys) or arginine (Arg), A2 is an amino acid selected from the group consisting of basic amino acids, glutamic acid (Glu), glycine (Gly) and aspartic acid (Asp), A3 is an amino acid selected from the group consisting of basic amino acids, proline (Pro), glutamic acid (Glu) and glutamine (Gln), A4 is an amino acid selected from the group consisting of basic amino acids, glutamic acid (Glu), glycine (Gly), serine (Ser) and valine (Val), and a pharmaceutically acceptable carrier. Excerpt(s): This is a continuation of International Application No. PCT/FR00/02786, with an international filing date of Oct. 6, 2000, which is based on French Patent Application No. 99/12714, filed Oct. 12, 1999. This invention concerns a new family of peptide molecules having the capacity especially of stimulating the expression of the cytokines of inflammation and promoting regeneration of tissues. The invention, thus, also pertains to pharmaceutical compositions containing at least one of the peptides. Known in the prior art are numerous angiogenic growth factors such as factors HARP, MK, FGF-1, FGF-2, VEGF, HIV1-tat, HIV2-tat, HGF, HB-EGF and angiogenin. Among these factors, HARP (Heparin Affin Regulatory Peptide), which is also called PTN (pleiotrophin) or HB-GAM (heparin binding-growth associated molecule), constitutes with MK (Midkine) a family of structurally related growth/differentiation factors that bind to heparin and having 50% homology in amino acids [L, 2]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pharmaceutical formulations of antineoplastic agents and processes of making and using the same Inventor(s): Ihnat, Peter M.; (Brooklyn, NY), Radhakrishnan, Vinay; (Laurence Harbor, NJ), Ugwu, Sydney; (Wheeling, IL), Witchey-Lakshmanan, Leonore C.; (Piscataway, NJ) Correspondence: Schering-plough Corporation; Patent Department (k-6-1, 1990); 2000 Galloping Hill Road; Kenilworth; NJ; 07033-0530; US Patent Application Number: 20040043001 Date filed: February 21, 2003 Abstract: In its several embodiments, this invention discloses a pharmaceutical formulation comprising at least one antineoplastic agent or a pharmaceutically acceptable salt thereof, and at least one dissolution enhancing agent sufficient to substantially dissolve said at least one antineoplastic agent in at least one aqueous diluent, wherein said dissolution enhancing agent is urea, L-histidine, L-threonine, L-
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asparagine, L-serine, L-glutamine or mixtures thereof; a lyophilized powder comprising said pharmaceutical formulation, and articles of manufacture thereof. Excerpt(s): This application claims priority from U.S. provisional patent application, Serial No. 60/359,198 filed Feb. 22, 2002. The present invention pertains to pharmaceutical formulations comprising antineoplastic agents, such as Temozolomide, and dissolution enhancing agents. Antineoplastic agents are useful in cancer therapies against a wide array of cancer and other diseases. Temozolomide is one such antineoplastic agent. U.S. Pat. No. 6.096,759 lists a variety of antineoplastic agents including Temozolomide, the disclosure of which is incorporated herein by reference. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical tryptophan containing dipeptide compositions and methods of use thereof Inventor(s): Green, Lawrence; (Tacoma, WA), Sinackevich, Nicolay V.; (St. Petersburg, RU) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20030198617 Date filed: June 6, 2002 Abstract: The present invention provides compositions and methods for treatment of a variety of disease states. The methods generally comprise administering to a host a therapeutically effective amount of a dipeptide having the formula X-Tryptophan or a pharmaceutically acceptable salt thereof, wherein x is glutamine, glutamate, leucine, or isoleucine. The present invention is useful for treatment of infections hyperimmune states, immunodeficiencies, and the like. Excerpt(s): This application is a continuation-in-part of U.S. patent application No. (U.S. Ser. No.) 08/075,842, filed Jun. 10, 1993, and U.S. Ser. No. 07/783,518, filed Oct. 28, 1991, which are continuations of U.S. Ser. No. 07/678,129, filed Apr. 1, 1991, now abandoned; and a continuation-in-part of U.S. Ser. No. 08/026,341, filed Mar. 4, 1993, each of which is incorporated herein by reference. The present invention relates generally to pharmaceutical compositions containing peptides having immunomodulating properties. More particularly, the present invention relates to pharmaceutical compositions of tryptophan-containing dipeptides and methods of use thereof. The immune system performs critical functions in animals, including humans. These functions include, e.g., preventing and combating infection, surveillance and immunoablation of tumors, and the like. A loss of immune system activity often results in serious and life-threatening diseases. Such functional abnormalities may be present in any of the components of the immune system, e.g., granulocytes, lymphocytes, complement, etc. Animals having dysfunctional immune systems may be at increased risk for malignancies and infections. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Physiological medium for perfusing, preserving and storing isolated cell, tissue and organ samples Inventor(s): Rees, Douglas; (London, GB) Correspondence: Thompson Coburn, Llp; One Firstar Plaza; Suite 3500; ST Louis; MO; 63101; US Patent Application Number: 20030077655 Date filed: September 3, 2002 Abstract: A physiological liquid medium is provided having the basic, synergistic components to allow its universal application in preserving cellular and functional integrity in vitro of different cell, tissue and organ types isolated from different mammalian species. The medium comprises an aqueous solution in sterile purified water of: i) a salt component comprising: a) from 100 to 150 mmoles/L of sodium ions, b) from 2.5 to 6.2 mmoles/L of potassium ions, c) from 1.0 to 2.5 mmoles/L of calcium ions, d) from 0.4 to 25 mmoles/L of magnesium ions, and e) from 96 to 126 mmoles/L of chloride ions; ii) a buffer component comprising: f) from 21 to 27 mmoles/L of bicarbonate ions, and g) from 1 to 12 mmoles/L of TES, MOPS or BES; iii) a substrate component comprising: h) 2 to 11 mmoles/L of glucose, I) 50 to 150.mu.moles/L of glycerol and j)7 zo 15.mu.moles/L of choline; iv) an amino acid component comprising: k) 5 to 400.mu.moles/L of glutamate, 1) 5 to 200.mu.moles/L of aspartate and m) 100 to 2000.mu.moles/L of glutamine; v) a co-enzyme component comprising: n) 1 to 120 nmoles/L of thiamine cocarboxylase; vi) a vitaminoid component comprising: o) 40 to 70.mu.moles/l of D- or DL- or L-carnitine; vii) a protein component comprising: p) 5 to 200 m I.U./L of porcine or human insulin. Excerpt(s): The present invention relates to the formulation of a physiological liquid medium having the basic, synergistic components to allow its universal application in preserving cellular and functional integrity in vitro of different cell, tissue and organ types isolated from different mammalian species. Historically, the design of physiological perfusion solutions dates back to the thesis proposed by the French physiologist, Claude Bernard in the eighteen seventies who put forward his theory on the milieu intriur, basically purporting that to maintain the whole (person) one should ensure that the surrounding extracellular environment should be balanced in all respects. Unfortunately, the misinterpretation or misconception of Bernard's milieu intriur has led researchers to confuse the extracellular with the intracellular phases of cell function and largely to overlook the need to maintain the cell as a whole entity. The basic salt solutions currently used for in vitro or isolated organ/tissue studies derive from the simple formulation used by Sidney Ringer for the isolated perfused frog heart. Similar, empirically contrived, basic salt solutions have been utilised for isolated mammalian preparations. The conventional use of phosphate/bicarbonate buffered salines was instigated by Krebs and Henseleit (Z. Physiol. Chem. 210: 33-66) for studies on isolated homogenates of mitochondria, ie. intracellular organelles, from pigeon liver. Later, Krebs, in his classical paper (Biochem. Biophys. Acta. 4: 249-269) on the analysis of oxygen consumption in tissue slices from different organs in a variety of animal species, acknowledged that substrate depletion in isolated tissue/organ preparations over time was a consideration that had not been addressed in the composition of previous physiological solutions. As has already been demonstrated, a correct interpretation of Bernard's hypothesis necessitates that the whole cell should subtend metabolic homeostasis. Traditionally, phosphate/bicarbonate buffers have been used for sixty years and are still currently used, with questionable validity, in perfusion/preservation solutions for mammalian and human tissues/organs. It is of interest to note that it has
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been known for 40 years that inorganic phosphate ions inhibit glycolysis and oxidative phosphorylation, creatine kinase and the enzymes involved in oxygen free radical scavenging, the latter being implicated in reperfusion injury and oedema formation in numerous organ systems. Maintenance of pH over time is further complicated by the instability of phosphate-buffered perfusion and preservation solutions caused by the precipitation of calcium phosphate and bicarbonate, accentuated by the change in their dissociation constants over the temperature range 4-37.degree. C. GB-A-2 270 614 describes an aqueous solution for the perfusion, storage and reperfusion of organs comprising calcium, potassium and magnesium chlorides, histidine, mannitol, lactiobionate, glutamate and glutathione. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Plant glutamine:fructose-6-phosphate amidotransferase nucleic acids Inventor(s): Dhugga, Kanwarpal S.; (Johnston, IA), Fallis, Patricia Lynne; (Polk City, IA), Nichols, Scott E.; (Westchester, PA), Wang, Tie; (Des Moines, IA) Correspondence: Pioneer Hi-bred International INC.; 7100 N.W. 62nd Avenue; P.O. Box 1000; Johnston; IA; 50131; US Patent Application Number: 20030177534 Date filed: December 17, 2002 Abstract: Isolated nucleic acid molecules are provided that encode maize glutamine:fructose-6-phosphate amidotransferase (GFAT) and variant GFAT proteins. These nucleic acid molecules can be used to produce transgenic plants that synthesize cationic starch. Also provided are vectors capable of expressing such nucleic acid molecules, host cells containing such vectors, and polypeptides encoded by such nucleic acids. Excerpt(s): This application is a continuation of co-pending U.S. patent application Ser. No. 09/379,779 filed Aug. 24, 1999, which application claims the benefit of U.S. Patent Application No. 60/097,881 filed Aug. 25, 1998, now abandoned, which is herein incorporated by reference. The present invention relates generally to methods of regulating the starch composition of plants. In particular, the present invention relates to a novel glutamine:fructose-6-phosphate amidotransferase (GFAT) nucleic acid, variant forms of the nucleic acid, and the use of such GFAT nucleic acids to produce plants that synthesize cationic starch. Due to its unique physical properties, starch is not only used in food products, but has a variety of industrial applications, including paper production, textiles, adhesives, flocculants, and building materials (see, for example, Kirby, "Non-Food Uses of Starch," in Developments in Carbohydrate Chemistry (Alexander and Zobel, eds.), pages 371-386 (The American Association of Cereal Chemists 1992); Watson, "Corn Marketing, Processing, and Utilization," in Corn and Corn Improvement (Sprague and Dudley, eds.), pages 881-940 (American Society of Agronomy, Inc. et al., 1988)). Plant starch for non-food use is obtained mainly from maize, potato, tapioca, and wheat. Barley, rice, and sago palm are considered as secondary sources of starch. In the United States, corn provides over 95% of the raw material for starch. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Polypeptide production in animal cell culture Inventor(s): Chen, Mary; (Burlingame, CA), Forman, Lawrence W.; (Sunnyvale, CA) Correspondence: Quine Intellectual Property Law Group, P.C.; P O Box 458; Alameda; CA; 94501; US Patent Application Number: 20040048368 Date filed: August 8, 2003 Abstract: A method-of producing a polypeptide in fed batch cell culture is provided which involves an initial cell growth phase and a distinct production phase. In the initial growth stage, animal cells having nucleic acid encoding the polypeptide are cultured at a starting osmolality of about 280-330 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. This is followed by a production phase, where the cultured animal cells of the growth phase are inoculated at a cell seed density of at least 1.0.times.10.sup.6 cells/mL and the cells are cultured at a starting osmolarity of about 400-600 mOsm in the presence of a concentration of glucose controlled throughout the culturing to be within a range between about 0.01 and 1 g/L. Preferably, the glutamine concentration in the cell culture medium is simultaneously controlled in order to curtail production of lactic acid and ammonia which result from unnecessarily high glutamine concentrations. During the growth phase, production of potentially detrimental metabolic waste products, such as lactic acid, is controlled thereby curtailing the increase of osmolality due to accumulation and neutralization of waste products. Thus, the cell growth can be improved. In the production phase, the cell culture conditions are modified in order to arrest or reduce cell growth and thereby direct nutrient utilization toward production, as opposed to cell growth. Overall, it is intended that the method results in an improvement in specific productivity, reduction in production run times and/or an increase in final product concentration. Excerpt(s): This invention relates to a method of improving polypeptide production in animal cell culture. In particular, it is directed to a method of culturing mammalian cells under conditions wherein the glucose concentration in the cell culture medium and the osmolality of the medium are controlled, so as to either promote cell growth or to promote recombinant polypeptide production. With the advent of recombinant DNA technology the number of polypeptides which are able to be produced in recombinant cell culture has greatly increased. While some recombinant DNA techniques rely on bacterial or yeast cells for the production of polypeptides, production of polypeptides in animal cells (especially mammalian cells) is becoming widespread, particularly for the production of mammalian polypeptides. Similarly, cell fusion techniques for preparing hybridomas, which may be cultured to produce monoclonal antibodies (MAbs), are widely used. Accordingly, techniques have been developed for enhancing cell growth and/or polypeptide production by such genetically modified animal cells. Several groups have looked at the effects of osmolality on cell growth and polypeptide production. See, for example, Stubblefield et al., Cancer Research, 20:1646-1655 (December 1960); Garcia-Perez et al., Journal of Biological Chemistry, 264(28):1681516821 (1989); Miner et al., Invasion Metastasis, 1:158-174 (1981); GB 2,251,249; EP 481,791; U.S. Pat. No. 5,151,359; U.S. Pat. No. 4,724,206; U.S. Pat. No. 5,122,469; and WO 89/04867. Various osmolality ranges for cell growth or polypeptide production are recommended and, generally, the osmolality of the cell culture medium is increased via the addition of NaCl or amino acids. However, these publications fail to disclose a method of controlling the osmolality of the cell culture medium by controlling the addition of the primary energy source, glucose, to the cell culture medium.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Process for differential diagnosis of Alzheimer's dementia in patients exhibiting mild cognitive impairment Inventor(s): Jackowski, George; (Kettleby, CA), Takahashi, Miyoko; (North York, CA) Correspondence: Michael A. Slavin, ESQ.; Mchale & Slavin, P.A.; Suite 402; 4440 Pga Boulevard; Palm Beach Gardens; FL; 33410; US Patent Application Number: 20030064416 Date filed: September 17, 2002 Abstract: A method for determining those patients suffering from mild cognitive impairment (MCI) who have a likelihood of progressing to Alzheimer's disease (AD) is disclosed. The method involves directly detecting the presence of a biochemical marker, specifically human glutamine synthetase, in bodily fluid, preferably blood or a blood product. The detection is by an immunoassay incorporating an antibody specific to human glutamine synthetase. In addition, a method for distinguishing between AD and non-AD dementia is disclosed. Excerpt(s): This application is a continuation-in-part of Ser. No. 09/971,740, filed Oct. 4, 2002, which is a continuation of Ser. No. 09/842,079, filed Apr. 25, 2001, now U.S. Pat. No. 6,451,547, Sep. 17, 2002, the contents of which are herein incorporated by reference in their entirety. The present invention relates to a method for the diagnosis of Alzheimer's dementia (AD). The invention particularly relates to a process for quantifying the presence of at least one biochemical marker associated with Alzheimer's dementia. More particularly, the invention relates to either a central laboratory or pointof-care immunoassay which is capable of the early differentiation of patients characterized as suffering from mild cognitive impairment (MCI) who will go on to develop Alzheimer's dementia. This differentiation is carried out by utilizing unique antibodies which enable the differential diagnosis of Alzheimer's versus nonAlzheimer's forms of dementia. The assay provides an ability to associate non-demented patients exhibiting symptoms diagnostic of MCI with various predictors associated with Alzheimer's dementia. The social impact of this disease is enormous, caused by the burden placed on caregivers, particularly in the latter stages of the disease. The substantial economic costs are largely related to supportive care and institutional admission. The rapidly increasing proportion of elderly people in society means that the number of individuals affected with AD will grow dramatically, therefore finding an early accurate diagnosis and a cure for AD is becoming an issue of major importance world wide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Processes for clonal growth of hepatic progenitor cells Inventor(s): Kubota, Hiroshi; (Chapel Hill, NC), Reid, Lola M.; (Chapel Hill, NC) Correspondence: Patent Adminstrator; Katten Muchin Zavis Rosenman; 525 West Monroe Street; Suite 1600; Chicago; IL; 60661-3693; US Patent Application Number: 20030032182 Date filed: May 1, 2002
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Abstract: A method of propagating mammalian endodermally derived progenitors such as hepatic progenitors, their progeny, or mixtures thereof is developed which includes culturing mammalian progenitors, their progeny, or mixtures thereof on a layer of embryonic mammalian feeder cells in a culture medium. The culture medium can be supplemented with one or more hormones and other growth agents. These hormones and other growth agents can include insulin, dexamethasone, transferrin, nicotinamide, serum albumin,.beta.-mercaptoethanol, free fatty acid, glutamine, CUSO.sub.4, and H.sub.2SeO.sub.3. The culture medium can also include antibiotics. Importantly, the culture medium does not include serum.The invention includes means of inducing the differentiation of the progenitors to their adult fates such as the differentiation of hepatic progenitor cells to hepatocytes or biliary cells by adding, or excluding epidermal growth factor, respectively.The method of producing mammalian progenitors is useful in that the progenitors can be used subsequently in one or more of the following processes: identification of growth and differentiation factors, toxicological studies, drug development, antimicrobial studies, or the preparation of an extracorporeal organ such as a bioartificial liver. Excerpt(s): The present invention relates to novel conditions for clonal growth of mammalian hepatic progenitors, including pluripotent cells, stem cells, and other early hepatic progenitor cells. In particular, the invention relates to methods of propagating hepatic progenitor cells using defined culture medium and feeder cells in co-cultures. Moreover, the invention relates to the cells used as feeders and capable of sustaining hepatic progenitor cell growth. Identification of multipotential progenitor cell populations in mammalian tissues is important both for clinical and commercial interests and also for understandings of developmental processes and tissue homeostasis. Progenitor cell populations are ideal targets for gene therapy, cell transplantation and for tissue engineering of bioartificial organs (Millar, A D. 1992 Nature 357, 455; Langer, R. and Vacanti, J. P. 1993 Science 260, 920; Gage, F. H. 1998 Nature 392, 18). The existence of tissue-specific, "determined" stem cells or progenitors having high growth potential and/or pluripotentiality is readily apparent from studies on hematopoictic stem cells (Spangrude, G. J. et al. 1988 Science 241, 58), neuronal stem cells (Davis, A. A., and Temple, S. 1994 Nature 372, 263; Stemple, D. L., and Anderson, D. J. 1992 Cell 71, 973) and epidermal stem cells (Jones, P. H. and Watt, F. M. 1993 Cell 73, 713), each having been identified clonally by using the particular methods appropriate for that tissue. These progenitors are regarded as the cells responsible for normal hematopoietic, neuronal or epidermal tissue homeostasis and for regenerative responses after severe injury (Hall, P. A., and Watt, F. M. 1989 Development 106, 619). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
STABILIZED ANTITHROMBIN III PREPARATION Inventor(s): ROMISCH, JURGEN; (MARBURG, DE), STAUSS, HARALD; (DAUTPHETAL, DE) Correspondence: Finnegan, Henderson, Farabow, Garrett &; Dunner Llp; 1300 I Street, NW; Washington; DC; 20005; US Patent Application Number: 20020172933 Date filed: December 7, 1999 Abstract: A stabilized antithrombin III preparation is described which is protected against a loss of action during pasteurization by the addition of stabilizers which consist of one or more saccharides in a mixture with more than 0.5 mol/l of one or more amino
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acids from the group consisting of arginine, lysine, histidine, phenylalanine, tryptophan, tyrosine, aspartic acid and its salts or glutamic acid and its salts, it also being possible to additionally add glycine or glutamine to each of these amino acids. Excerpt(s): The invention relates to a stabilized antithrombin III preparation which is protected against a loss of action during pasteurization by the addition of stabilizers, and to a process for virus inactivation of an antithrombin III preparation of this type. Antithrombin III (ATIII) is one of the most important plasmatic inhibitors. ATIII belongs to the family of serine protease inhibitors, which with their "target proteases" enter into a complex approximating the covalent bond. This complex is very stable under physiological conditions and as a rule is rapidly eliminated from the blood circulation. The reaction between ATIII and the protease is drastically accelerated by heparin, the ATIII undergoing a slight change in conformation after association with the glycosaminoglycan and thus being able to enter into an accelerated reaction with the protease. Physiologically, these processes play a role, particularly on cell surfaces which contain glycosaminoglycans, e.g. of the heparin sulfate type, and thus represent a barrier of the cells and tissue against excessive proteolytic activity. In addition, however, plasmatic coagulation, and its regulation, is also of great importance. The regulatory function of this inhibitor is particularly clear when the ATIII plasma levels fall, as is observed in many illnesses and particularly drastically, for example, in the case of disseminated intravascular coagulation (DIC). Even a shortfall of 70% of the corresponding plasma concentration is associated with a drastic increase in the probability of mortality. A predominance of clotting processes frequently leads to thrombotic occlusions of vessels and thus to organ failure. Correspondingly, administration of ATIII concentrates from human plasma has proven very helpful, particularly in cases of inherited and acquired deficiency states. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Supplementation of equine feedstuffs Inventor(s): Harris, Patricia Ann; (Leicestershire, GB), Harris, Roger C; (Leicestershire, GB) Correspondence: Fulbright & Jaworski, Llp; 1301 Mckinney; Suite 5100; Houston; TX; 77010-3095; US Patent Application Number: 20030162723 Date filed: February 18, 2003 Abstract: The present invention provides equine feedstuffs and methods by which plasma glutamine concentrations in equine animals can be increased or maintained. The present invention provides equine feedstuffs with supplemented glutamine and with optional high levels of fat or oil. Glutamine supplementation provides a pharmacological benefit to the equine animal, for example in respect of one or more or over-training, infection, other stressful conditions or catabolic stress. Excerpt(s): The present invention provides equine feedstuffs and methods by which plasma glutamine concentrations in equine animals can be increased or maintained. Glutamine is a neutral amino acid which is readily transported across plasma membranes. As an important intermediate in a number of metabolic pathways, cellular utilisation of glutamine can far exceed that of other amino acids especially within intestinal and immune cells. Glutamine is important in the transport of amino nitrogen and ammonia, as a substrate in gluconeogenesis and ammoniagenesis, as a fuel source
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for rapidly dividing cells and may also be involved in the regulation of protein synthesis. Under normal conditions, the body's requirement for glutamine is met by synthesis within specific tissues, principally skeletal muscle, and, to some extent, from dietary protein. Glutamine is, however, the preferential fuel source for intestinal enterocytes. The uptake of dietary glutamine by these cells is thought to be substantial, and that comparatively little is released into the bloodstream. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Synergistically acting herbicidal mixtures Inventor(s): Deyn, Wolfgang Von; (Neustadt, DE), Kibler, Elmar; (Hassloch, DE), Landes, Max; (Gonnheim, DE), Otten, Martina; (Ludwigshafen, DE), Sievernich, Bernd; (Iggelheim, DE), Vantieghem, Herve; (Stutensee, DE), Walter, Helmut; (Obrigheim, DE), Westphalen, Karl-Otto; (Speyer, DE) Correspondence: Keil & Weinkauf; 1350 Connecticut Avenue, N.W.; Washington; DC; 20036; US Patent Application Number: 20030203819 Date filed: January 23, 2003 Abstract: A synergistic herbicidal mixture comprisingA) at least one 3-heterocyclylsubstituted benzoyl derivative of the formula I 1 in which the variables have the following meanings:R.sup.1, R.sup.3 are hydrogen, halogen, alkyl, halogenalkyl, alkoxy, halogenalkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl;R.sup.2 is a heterocyclic radical selected from the group: thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isoxazol-3-yl, isoxazol-4yl, isoxazol-5-yl, 4,5-dihydroisoxazol-3-yl, 4,5-dihydroisoxazol-4-yl and 4,5dihydroisoxazol-5-yl, it being possible for these to be unsubstituted or mono- or polysubstituted by halogen, alkyl, alkoxy, haloalkyl, haloalkoxy or alkylthio;R.sup.4 is hydrogen, halogen or alkyl;R.sup.5 is alkyl;R.sup.6 is hydrogen or alkyl;or one of its environmentally compatible salts; andB) a synergistically effective amount of at least one herbicidal compound from the group of the acetyl-CoA carboxylase inhibitors (ACC), acetolactate synthase inhibitors (ALS), amides, auxin herbicides, auxin transport inhibitors, carotenoid biosynthesis inhibitors, enolpyruvylshikimate-3-phosphate synthase inhibitors (ESPS), glutamine synthetase inhibitors, lipid biosynthesis inhibitors, mitosis inhibitors, protophorphyrinogen [sic] IX oxidase inhibitors, photosynthesis inhibitors, synergists, growth substances, cell wall biosynthesis inhibitors and a variety of other herbicides.Compositions comprising these mixtures, processes for the preparation of these compositions, and their use for controlling undesired plants. Excerpt(s): B) a synergistically effective amount of at least one herbicidal compound from the group of the acetyl-CoA carboxylase inhibitors (ACC), acetolactate synthase inhibitors (ALS), amides, auxin herbicides, auxin transport inhibitors, carotenoid biosynthesis inhibitors, enolpyruvylshikimate 3-phosphate synthase inhibitors (ESPS), glutamine synthetase inhibitors, lipid biosynthesis inhibitors, mitosis inhibitors, protoporphyrinogen IX oxidase inhibitors, photosynthesis inhibitors, synergists, growth substances, cell wall biosynthesis inhibitors and a variety of other herbicides. The invention furthermore relates to herbicidal compositions comprising a herbicidally active amount of a synergistic herbicidal mixture as defined above and at least one liquid and/or solid carrier and, if desired, at least one surfactant. Moreover, the invention relates to processes for the preparation of these compositions and to a method of controlling undesirable vegetation.
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Synthesis of 2-oxoglutaramate from L-glutamine Inventor(s): Lalonde, James J.; (Boston, MA) Correspondence: Ppg Industries, INC.; Intellectual Property Department; One Ppg Place; Pittsburgh; PA; 15272; US Patent Application Number: 20030032149 Date filed: August 13, 2001 Abstract: A fermentation method for the production of 2-oxoglutaramic acid including the step of incubating L-glutamine in the presence of bacteria of the genera Providencia and Proteus, including Providencia sp. PCM-1270 and PCM-1298 and Proteus mirabilis PCM-1353. The incubation typically is conducted in an aqueous slurry of solid Lglutamine, a buffer, catalase and the bacteria cells. Typically, a wet cell pellet mass of cells of at least 1% by weight of the incubation mixture is included in the L-glutaminecontaining incubation mixture. A bacteria culture containing the bacteria and Lglutamine is provided along with a bacteria culture containing the bacteria and 2oxoglutaramic acid, the product of the above-described method. Excerpt(s): The present invention is directed to a method for producing 2oxoglutaramate from L-glutamine and the product of that method. 2-oxoglutaramate (also known as 2-hydroxy-5-oxoproline and.alpha.-ketoglutaramic acid) is synthesized and metabolized in plants by the sequential action of transaminase and hydrolase enzymes. Similar transaminase and hydrolase enzymes and 2-oxoglutaramate have been identified in animal livers and kidneys. These enzymes and 2-oxoglutaramate were partially characterized in Meister, A, "Enzymatic Preparation of a-Keto Acids," J. Biochem. 197:304 (1952). The compound 2-oxoglutaramate has substantial agricultural uses as a plant growth regulator. However, economical and/or safe methods for the production of 2-oxoglutaramate do not exist. Meister, A, "Preparation and Enzymatic Reactions of the Keto Analogues of Asparagine and Glutamine J. Biol. Chem.," 20, 571 (1953), describes the conversion of L-glutamine to 2-oxoglutaramate with rattlesnake (Crotalus adamanteus) and other snake venoms. While effective, use of snake venom for preparative conversion of L-glutamine to 2-oxoglutaramate is commercially impracticable. Oxidation of alpha amino acids by non-enzymatic means requires the use of highly reactive, inorganic oxidants such as Fremy's salt (A. Garcian-Raso, P. M. Dey, and J. M. Saa, J. Org. Chem. 1986, 51, 4285-4287). Bacteria of the Genera Proteus, Providencia and Morganella are known to deaminate phenylalanine to phenylpyruvic acid. Members of these genera also have the ability to convert amino acids other than phenylalanine to their corresponding.alpha.-keto acid. U.S. Pat. No. 5,728,555 discloses a recombinant L-aminodeaminase (Lad) gene derived from Proteus myxofaciens purportedly exhibiting the ability to convert small amounts of L-glutamine to another product. However, there is no indication that P. myxofaciens, the source of the Lad gene described in that patent, can convert L-glutamine to 2-oxoglutaramate and not subsequently convert the product to a secondary product. U.S. Pat. Nos. 4,614,714, 4,783,404 and 5,801,035 disclose L-amino acid oxidases of Streptomyces, Cryptococcus and Trichoderma species. None of the L-amino acid oxidases of the above-referenced patents are known to have the ability to convert L-glutamine to 2-oxoglutaramate in preparative quantities. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Transgenic mammals expressing polyglutamine Inventor(s): Cummings, Christopher J.; (Brookline, MA), Watase, Kei; (Houston, TX), Zoghbi, Huda Y.; (Houston, TX) Correspondence: Palmer & Dodge, Llp; Kathleen M. Williams; 111 Huntington Avenue; Boston; MA; 02199; US Patent Application Number: 20040045046 Date filed: June 11, 2003 Abstract: The present invention utilizes a "knock-in" approach to provide a transgenic mammal containing integrated into its genome a repeating nucleotide sequence encoding a polyglutamine comprising at least about 154, preferably at least about 160, 200, 300, 400, 500, and up to 600 or more contiguous glutamine residues. The transgenic mammals normally display observable phenotypic changes. As such, they may serve as a model for disease processes in humans for such diseases as spinobulbar muscular atrophy (SBMA), Huntington's disease (HD), dentatorubral pallidoluysian atrophy (DRPLA), and the spinocerebellar ataxias types 1, 2, 3, 6, 7, and 17. As a result of displaying pathology indicative of a human disease, the efficacy of an agent for treating human disease may be tested in the transgenic mammals. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/387,939, filed Jun. 11, 2002, the contents of which are incorporated herein in their entirety. The present invention relates to novel transgenic non-human mammals. In particular, it relates to transgenic non-human mammals that express a protein involved in a neurological disorder or a protein having a polyglutamine region that mediates a disorder entirely or in part. The present invention also features transgenes and genetic constructs useful in the preparation of transgenic mammals, and methods of screening for biologically active agents, including those useful in the treatment of a neurological disorder. Spinocerebellar ataxia type I (SCA1) is a dominantly inherited late-onset neurodegenerative disorder characterized by progressive ataxia, dysarthria and swallowing difficulties (Zoghbi et al., (1995) Semin. Cell Biol. 6, 29-35), and is one of nine established neurodegenerative diseases who's etiology is linked to the expansion of a CAG repeat the encodes for polyglutamine in the respective disease proteins. The other diseases include SCA2, 3, 6, 7, and 17, as well as Huntington's disease (HD), spinobulbar muscular atrophy (SBMA) and dentatorubralpallidoluysian atrophy (DRPLA) (Zoghbi and Orr, 2000, Ann. Rev. Neurosci. 23:217). The onset of SCA1 clinical symptoms occurs usually in the third or fourth decade of life, although juvenile cases have been observed (Zoghbi, H. Y., et al. (1998) Ann. Neurol., 23, 580-584). The disease worsens progressively over 10 to 15 years, leading eventually to death due to bulbar dysfunction. Neuropathologically, SCA1 is characterized by selective degeneration of cerebellar Purkinje cells and neurons of the inferior olive and brainstem. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Treatment of mycobacterium tuberculosis with antisense polynucleotides Inventor(s): Harth, Gunter; (Los Angeles, CA), Horwitz, Marcus A.; (Los Angeles, CA), Zamecnik, Paul C.; (Boston, MA) Correspondence: Gates & Cooper Llp; Howard Hughes Center; 6701 Center Drive West, Suite 1050; Los Angeles; CA; 90045; US Patent Application Number: 20040033972 Date filed: August 29, 2002 Abstract: Methods of inhibiting the proliferation of Mycobacterium tuberculosis comprising contacting Mycobacterium tuberculosis with an effective amount of a polynucleotide complementary to an mRNA transcript expressed by Mycobacterium tuberculosis are provided. Typical methods of the invention utilize phosphorothioate modified antisense polynucleotides (PS-ODNs) against the mRNA of M.tuberculosis genes such as glutamine synthetase, aroA,ask, groES, and the genes of the Antigen 85 complex. Excerpt(s): This application claims the benefit of U.S. provisional patent application No. 60/171,929, filed Dec. 22, 1999, the entire contents of which are incorporated herein by reference. The present invention relates to the use of antisense polynucleotides as prophylactic and therapeutic agents in the treatment of Mycobacterium tuberculosis infection. TB is acquired by the respiratory route; actively infected individuals spread this infection efficiently by coughing or sneezing "droplet nuclei" which contain viable bacilli. Overcrowded living conditions and shared air spaces are especially conducive to the spread of TB, underlying the increase in instances that have been observed in the U.S. in prison inmates and among the homeless in larger cities. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Variant integrin polypeptides and uses thereof Inventor(s): Arnaout, M. Amin; (Chestnut Hill, MA), Li, Rui; (Medford, MA), Xiong, Jian-Ping; (Quincy, MA) Correspondence: Fish & Richardson, PC; 4350 LA Jolla Village Drive; Suite 500; San Diego; CA; 92122; US Patent Application Number: 20030109691 Date filed: May 10, 2002 Abstract: Polypeptides comprising all or part of a variant integrin.alpha. subunit A domain and its flanking region are described. In solution or in membrane-associated form, the A domain polypeptides of the invention exists predominantly in a high affinity conformation. In the polypeptides of the invention, referred to as variant integrin polypeptides, a crucial isoleucine or glutamic acid residue is altered. For example, the glutamic acid can be either deleted or replaced with different amino acids residue, e.g., glutamine, aspartic acid, or alanine The variant integrin polypeptides of the invention selectively impair binding of activation-dependent ligands, but not independent ligands. They are useful in screening assays for the identification of molecules that enhance binding of variant polypeptides with impaired binding. In addition, they are useful in distinguishing between activation-dependent ligands and activation-independent ligands. They are also useful for generating antibodies, e.g., monoclonal antibodies, which bind to the impaired form of an integrin. Some such
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antibodies recognize an epitope that is either not present or not accessible on an integrin that is in the high affinity conformation. The variant integrin polypeptides of the invention can be derived from any integrin.alpha. subunit that could be used therapeutically. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/758,493, filed Jan. 11, 2001; which claims priority from Provisional Application Serial No. 60/221,950, filed Jul. 31, 2000, the contents of which are hereby incorporated by reference. Integrins are heterodimeric receptors that mediate a wide variety of important interactions both between cells and between cells and the extracellular matrix via ligand binding. All integrins have an.alpha. subunit and a.beta. subunit. Within the.alpha. subunit a region referred to as the A domain (or I domain) is known to be an important mediator of ligand binding. A similar region, the A-like domain, is present in many.beta. subunits. These heterodimeric.alpha.beta. integrins contain a von Willebrand Factor (vWF) A domain,.beta.A, in their.beta. subunits; and nine integrins also contain a second such domain,.alpha.A, in their.alpha. subunits. Many integrins are thought to exist in two conformations, a low affinity state (the "closed" or "unliganded" conformation") and a high affinity state (the "open" or "liganded" conformation), the latter of which is responsible for high affinity ligand binding. Integrins transduce signals that mediate the effects of the matrix on the physiological activity of cells (e.g., motility, proliferation, differentiation). Moreover, integrins play a role in inflammation and in oncogenic cell transformation, metastasis, and apoptosis. Thus, there is considerable interest in identifying compounds that can activate or inhibit the activity of one or more integrins. 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 glutamine, 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 “glutamine” (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 glutamine. You can also use this procedure to view pending patent applications concerning glutamine. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 7. BOOKS ON GLUTAMINE Overview This chapter provides bibliographic book references relating to glutamine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on glutamine 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 “glutamine” (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 glutamine: •
Numb Toes and Aching Soles: Coping with Peripheral Neuropathy Source: San Antonio, TX: MedPress. 1999. 300 p. Contact: Available from MedPress. P.O. Box 691546, San Antonio, TX 78269. (888) 6339898. Website: www.medpress.com. PRICE: $19.95 for soft back book; $29.95 for case bound book; plus shipping and handling. ISBN 0967110726. Summary: This book serves as a resource for people who experience pain related to peripheral neuropathy. About one half of peripheral neuropathies are related to complications from diabetes mellitus. The book focuses on traditional, conventional, and alternative treatments for neuropathic pain. The book begins with a chapter that defines peripheral neuropathy and discusses this condition in terms of its types, symptoms and effects, causes, and evaluation. The next chapter explains the physical and psychological aspects of peripheral neuropathic pain. The following chapter discusses medications for treating peripheral neuropathic pain, including nonopioid drugs, opioids, and topical
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medications. A discussion of nonopioid drug costs is included. The fourth chapter focuses on other medical therapies for treating peripheral neuropathic pain, including hematologic treatments such as plasmapheresis, immunosuppressant medications, and nerve based treatments such as nerve blocks and direct nerve stimulation. This is followed by a chapter on alternative treatments, including physical therapy; psychotherapeutic methods such as relaxation and meditation training, biofeedback, self hypnosis, and prayer; hyperbaric oxygen therapy; acupuncture; touch therapies such as massage, reflexology, Reiki, Qigong, and therapeutic touch; magnets; and chelation. Treating peripheral neuropathic pain with various nutrients (vitamins A, B, C, and E; minerals such as selenium, magnesium, chromium, and zinc; and herbs such as ginkgo biloba, St. John's wart, bioflavonoids, and others) is the topic of the next chapter. In addition, the chapter provides information on other supplements such as alpha-lipoic acid, gamma linolenic acid, acetyl-L-carnitine, N-acetyl cysteine, glutamine, coenzyme Q10, S-adenosylmethionine, dimethyl sulfoxide, and methyl sulfonyl methane. The focus of the next chapter is on experimental or unapproved drugs, including aldose reductase inhibitors; aminoguanidine; COX-2; ABT-594; SNX-111; lamotrigine; memantine; natural pain relievers such as bimoclomol, cannabinoids, endorphins, and nocistatin/OFQ2; nerve regenerating compounds such as NGF, IGF-1, neutrophin-3, and GPI 1046; nimodipine; peptide T; and PN 401. This is followed by a chapter that examines diabetes and HIV. Diabetes classifications and diabetic neuropathy (types, risk factors, blood sugar control, and treatment approaches) are discussed. The final chapter presents ways of coping with peripheral neuropathy, including exercising, using heat or cold therapy, creating conducive conditions for sleeping, avoiding certain foods, and selecting appropriate footwear. The book concludes with an index.
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 “glutamine” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “glutamine” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “glutamine” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Dexamethasone regulates glutamine synthetase expression in rat skeletal muscles (SuDoc NAS 1.26:182935) by NASA; ISBN: B00010OEP6; http://www.amazon.com/exec/obidos/ASIN/B00010OEP6/icongroupinterna
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Glutamate, Glutamine, Glutathione, and Related Compunds : Volume 113: Glutamente, Glutamine, Glutathione and Related Compounds by Nathan Colowick (Author), et al; ISBN: 0121820130; http://www.amazon.com/exec/obidos/ASIN/0121820130/icongroupinterna
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Glutamine and Glutamate in Mammals by Elling Kvamme (Editor); ISBN: 084936857X; http://www.amazon.com/exec/obidos/ASIN/084936857X/icongroupinterna
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Glutamine Metabolism in Mammalian Tissues by D. and Sies, H. Haussinger (Editor); ISBN: 0387134549; http://www.amazon.com/exec/obidos/ASIN/0387134549/icongroupinterna
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Glutamine Metabolism in Mammalian Tissues; ISBN: 3540134549; http://www.amazon.com/exec/obidos/ASIN/3540134549/icongroupinterna
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Glutamine Repeat and Neurodegenerative Diseases: Molecular Aspects by Peter S. Harper (Editor), Max F. Perutz (Editor); ISBN: 0198506856; http://www.amazon.com/exec/obidos/ASIN/0198506856/icongroupinterna
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Glutamine, Glutamate, and Gaba in the Central Nervous System by Leif Hertz (Editor), et al; ISBN: 047183517X; http://www.amazon.com/exec/obidos/ASIN/047183517X/icongroupinterna
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Glutamine, glutamate, and GABA in the central nervous system : proceedings of a satellite symposium of the 9th Meeting of the International Society for Neurochemistry on the metabolic relationship between Glutamine, Glutamate, and GABA in the Central Nervous System, held in Saskatoon, Saskatchewan, Canada, July 17-20, 1983; ISBN: 0845127063; http://www.amazon.com/exec/obidos/ASIN/0845127063/icongroupinterna
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Glutamine: Physiology, Biochemistry and Nutrition in Critical Illness (Medical Intelligence Unit) by Wiley W. Souba; ISBN: 1879702363; http://www.amazon.com/exec/obidos/ASIN/1879702363/icongroupinterna
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Glutamine--Metabolism, Enzymology, and Regulation by Enzymology, and regu International Symposium on Glutamine: Metabolism; ISBN: 0125060408; http://www.amazon.com/exec/obidos/ASIN/0125060408/icongroupinterna
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The Ultimate Nutrient: Glutamine/the Essential Nonessential Amino Acid by Judy Shabert, Nancy Ehrlich (Contributor); ISBN: 0895295881; http://www.amazon.com/exec/obidos/ASIN/0895295881/icongroupinterna
Chapters on Glutamine In order to find chapters that specifically relate to glutamine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and glutamine 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 “glutamine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on glutamine: •
Physiology of Digestion, Absorption, and Metabolism in the Human Intestine Source: in Preedy, V.R. and Watson, R.R., eds. Alcohol and the Gastrointestinal Tract. Boca Raton, FL: CRC Press. 1996. p. 79-110. Contact: Available from CRC Press. 2000 Corporate Boulevard NW., Boca Raton, FL 33431. (800) 272-7737 or (561) 994-0555. Fax (800) 374-3401. E-mail:
[email protected]. Website: http://www.crcpress.com. PRICE: $179.00. ISBN: 0849324807. Summary: This chapter, from a medical text on alcohol and the gastrointestinal tract, addresses the most significant features of digestion, absorption, and intestinal metabolism and how they are affected by alcohol consumption. The section on digestion and absorption in the small intestine covers protein, carbohydrate, fat absorption, water, and electrolytes. Other topics include the nutrition of the intestinal mucosa; and
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principal substrates for small intestinal metabolism, including glutamine, glutathione, nucleotides, arginine, urea and luminal protein. 4 figures. 5 tables. 253 references. •
Gastrointestinal and Pancreatic Disease Source: in Gottschlich, M.M.; Matarese, L.E.; and Shronts, E.P., eds. Nutrition Support Dietetics: Core Curriculum. 2nd ed. Silver Spring, MD: American Society of Parenteral and Enteral Nutrition. 1993. p. 275-310. Contact: Available from American Society of Parenteral and Enteral Nutrition (A.S.P.E.N.). 8630 Fenton Street, Suite 412, Silver Spring, MD 20910. (301) 587-6315. PRICE: $50 for A.S.P.E.N. members; $77 for non-members. Summary: This chapter, from a textbook of nutrition support dietetics, presents a detailed outline describing the nutritional support for gastrointestinal and pancreatic disease. Topics include the normal function of the gastrointestinal (GI) tract; specific gut fuels, including glutamine, protein, fiber, and short-chain fatty acids; common GI disorders, including esophageal perforation, esophageal obstruction, esophageal varices, esophageal resection, gastric surgery, inflammatory bowel disease, and malabsorption; short bowel syndrome (SBS); enteric fistulas; chylous ascites; and pancreatic disorders, including pancreatitis, and cystic fibrosis. For each disease or condition, the author covers nutritional management, including parenteral or enteral nutrition, physiology, pharmacologic treatment, and complications. The chapter concludes with a list of selfassessment questions. 44 references.
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CHAPTER 8. PERIODICALS AND NEWS ON GLUTAMINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover glutamine.
News Services and Press Releases One of the simplest ways of tracking press releases on glutamine 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 “glutamine” (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 glutamine. 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 “glutamine” (or synonyms). The following was recently listed in this archive for glutamine: •
Glutamine no help for dieting athletes: study Source: Reuters Health eLine Date: December 29, 2003
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Glutamine-antioxidant supplementation can reverse AIDS-wasting Source: Reuters Medical News Date: November 11, 1999
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Polyglutamine Peptides Linked To CNS Disorders Form Aggregates Source: Reuters Medical News Date: December 12, 1996 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. 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 “glutamine” (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 “glutamine” (or synonyms). If you know the name of a company that is relevant to glutamine, 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 “glutamine” (or synonyms).
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Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “glutamine” (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 glutamine: •
Case for the Gluten-Free Diet Or One Dietitian's Journey In the Gluten-Free Diet Maze Source: Lifeline. 19(1): 1-4. Winter 2000. Contact: Available from Celiac Sprue Association-United States of America, Inc. P.O. Box 31700, Omaha, NE 68131. (402) 558-0600. Website: www.csaceliacs.org. Summary: This newsletter article, written by a pediatric clinical dietitian, explores the use of the gluten free diet for the treatment of celiac disease (CD). Gluten is the substance that gives bread elasticity; structurally, gluten contains high glutamine and high proline storage proteins (prolamins) and is composed of two protein fractions, gliadin and glutenin. Gliadin is a toxic protein fraction in gluten; glutenin is found only in wheat, while gliadin is found in other grains and grasses. The author explains how toxic amino acid sequences are identified and discusses the role of total protein content in determining toxicity. The author then explores the variance in the recommendations for a safe gluten intake. One major reason for this variation is the unique response of each individual with CD; some patients are more sensitive to a lower level of gluten than others. Although clinical studies are very expensive to undertake, their results have demonstrated the need for dietary compliance, particularly to ensure adequate growth in children with CD. For adults, strict adherence to a diet free of toxic prolamins can reduce the risk for reduced bone mineralization, lymphoma, and other forms of cancer associated with CD. The author briefly reviews three hypotheses about how CD occurs: enzyme deficiency, lectin interaction, and immune mechanisms. The author concludes by proposing a different name for the CD diet therapy, since gluten free does not encompass the many other aspects that must be taken into consideration. 2 tables.
Academic Periodicals covering Glutamine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to glutamine. In addition to these sources, you can search for articles covering glutamine 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
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periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 9. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for glutamine. 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).
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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.
Researching Orphan Drugs Although the list of orphan drugs is revised on a daily basis, you can quickly research orphan drugs that might be applicable to glutamine by using the database managed by the National Organization for Rare Disorders, Inc. (NORD), at http://www.rarediseases.org/. Scroll down the page, and on the left toolbar, click on “Orphan Drug Designation Database.” On this page (http://www.rarediseases.org/search/noddsearch.html), type “glutamine” (or synonyms) into the search box, and click “Submit Query.” When you receive your results, note that not all of the drugs may be relevant, as some may have been withdrawn from orphan status. Write down or print out the name of each drug and the relevant contact information. From there, visit the Pharmacopeia Web site and type the name of each orphan drug into the search box at http://www.nlm.nih.gov/medlineplus/druginformation.html. You may need to contact the sponsor or NORD for further information. NORD conducts “early access programs for investigational new drugs (IND) under the Food and Drug Administration’s (FDA’s) approval ‘Treatment INDs’ programs which allow for a limited number of individuals to receive investigational drugs before FDA marketing approval.” If the orphan product about which you are seeking information is approved for
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marketing, information on side effects can be found on the product’s label. If the product is not approved, you may need to contact the sponsor. The following is a list of orphan drugs currently listed in the NORD Orphan Drug Designation Database for glutamine: •
Human growth hormone http://www.rarediseases.org/nord/search/nodd_full?code=763
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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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
•
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
•
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 “glutamine” (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 23114 66 352 54 363 23949
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 “glutamine” (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/.
The Genome Project and Glutamine In the following section, we will discuss databases and references which relate to the Genome Project and glutamine. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).22 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 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. 22 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “glutamine” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for glutamine: •
Glutamine:fructose-6-phosphate Amidotransferase 1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=138292
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Glutamine:fructose-6-phosphate Amidotransferase 2 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603865
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Pc2 Glutamine/q-rich-associated Protein Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607372
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Polyglutamine-binding Protein 1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300463
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Small Glutamine-rich Tetratricopeptide Repeat-containing Protein Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603419
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Splicing Factor, Proline- and Glutamine-rich Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605199
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Transfer Rna Glutamine 1 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=189919
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Transfer Rna Glutamine 2 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=189923
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Transfer Rna, Mitochondrial, Glutamine Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=590030 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
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•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
•
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “glutamine” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database23 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database24 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of 23
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 24 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “glutamine” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on glutamine 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 glutamine. 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 glutamine. 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 “glutamine”:
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Other guides Anemia http://www.nlm.nih.gov/medlineplus/anemia.html Cancer http://www.nlm.nih.gov/medlineplus/cancer.html Sickle Cell Anemia http://www.nlm.nih.gov/medlineplus/sicklecellanemia.html Sleep Disorders http://www.nlm.nih.gov/medlineplus/sleepdisorders.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 National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “glutamine” (or synonyms). The following was recently posted: •
American Gastroenterological Association medical position statement: short bowel syndrome and intestinal transplantation Source: American Gastroenterological Association - Medical Specialty Society; 2003 April; 6 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3795&nbr=3021&a mp;string=glutamine
•
Practice guidelines for the management of infectious diarrhea Source: Infectious Diseases Society of America - Medical Specialty Society; 2001 February; 21 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2791&nbr=2017&a mp;string=glutamine
•
Practice management guidelines for nutritional support of the trauma patient Source: Eastern Association for the Surgery of Trauma - Professional Association; 2001; 112 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2961&nbr=2187&a mp;string=glutamine
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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to glutamine. 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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WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to glutamine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with glutamine. 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 glutamine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at
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http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “glutamine” (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 “glutamine”. 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 “glutamine” (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 “glutamine” (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.25
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
25
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)26: •
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/
26
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries 275 •
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
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
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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GLUTAMINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaldehyde: A colorless, flammable liquid used in the manufacture of acetic acid, perfumes, and flavors. It is also an intermediate in the metabolism of alcohol. It has a general narcotic action and also causes irritation of mucous membranes. Large doses may cause death from respiratory paralysis. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetolactate Synthase: A flavoprotein that catalyzes the formation of acetolactate from 2 moles of pyruvate in the biosynthesis of valine and the formation of acetohydroxybutyrate from pyruvate and alpha-ketobutyrate in the biosynthesis of isoleucine. EC 4.1.3.18. [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] Acetylcysteine: The N-acetyl derivative of cysteine. It is used as a mucolytic agent to reduce the viscosity of mucous secretions. It has also been shown to have antiviral effects in patients with HIV due to inhibition of viral stimulation by reactive oxygen intermediates. [NIH] Acetylglucosamine: The N-acetyl derivative of glucosamine. [NIH]
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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] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenomatous Polyposis Coli: An autosomal dominant polyposis syndrome in which the colon contains few to thousands of adenomatous polyps, often occurring by age 15 to 25. [NIH]
Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Monophosphate: Adenylic acid. Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position. [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] Adhesives: Substances that cause the adherence of two surfaces. They include glues (properly collagen-derived adhesives), mucilages, sticky pastes, gums, resins, or latex. [NIH] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] 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
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epinephrine and norepinephrine. [NIH] Adsorption: The condensation of gases, liquids, or dissolved substances on the surfaces of solids. It includes adsorptive phenomena of bacteria and viruses as well as of tissues treated with exogenous drugs and chemicals. [NIH] Adsorptive: It captures volatile compounds by binding them to agents such as activated carbon or adsorptive resins. [NIH] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, oxidative metabolism, or cell respiration. [NIH] Aerobic Respiration: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as oxidative metabolism, cell respiration, or aerobic metabolism. [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] 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] Agmatine: Decarboxylated arginine, isolated from several plant and animal sources, e.g., pollen, ergot, herring sperm, octopus muscle. [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] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [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
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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] Alcohol Dehydrogenase: An enzyme that catalyzes reversibly the final step of alcoholic fermentation by reducing an aldehyde to an alcohol. In the case of ethanol, acetaldehyde is reduced to ethanol in the presence of NADH and hydrogen. The enzyme is a zinc protein which acts on primary and secondary alcohols or hemiacetals. EC 1.1.1.1. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] 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] 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] Alkalosis: A pathological condition that removes acid or adds base to the body fluids. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] 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] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments.
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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] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amber: A yellowish fossil resin, the gum of several species of coniferous trees, found in the alluvial deposits of northeastern Germany. It is used in molecular biology in the analysis of organic matter fossilized in amber. [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 Motifs: Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a conserved sequence which can be represented by a consensus sequence. [NIH]
Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amylase: An enzyme that helps the body digest starches. [NIH] Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anabaena: A genus of cyanobacteria consisting of trichomes that are untapered with conspicuous constrictions at cross-walls. A firm individual sheath is absent, but a soft covering is often present. Many species are known worldwide as major components of freshwater plankton and also of many saline lakes. The species Anabaena flos-aquae is responsible for acute poisonings of various animals. [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
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sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphase: The third phase of cell division, in which the chromatids separate and migrate to opposite poles of the spindle. [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] Anastomosis: A procedure to connect healthy sections of tubular structures in the body after the diseased portion has been surgically removed. [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] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anionic: Pertaining to or containing an anion. [EU] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Aniridia: A congenital abnormality in which there is only a rudimentary iris. This is due to the failure of the optic cup to grow. Aniridia also occurs in a hereditary form, usually autosomal dominant. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] Anthelmintic: An agent that is destructive to worms. [EU] Anthranilate Synthase: An enzyme that catalyzes the formation of anthranilate (oaminobenzoate) and pyruvic acid from chorismate and glutamine. Anthranilate is the biosynthetic precurser of tryptophan and numerous secondary metabolites, including inducible plant defense compounds. EC 4.1.3.27. [NIH] Anthropometry: The technique that deals with the measurement of the size, weight, and
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proportions of the human or other primate body. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] 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] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [NIH] Antidiabetic: An agent that prevents or alleviates diabetes. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antiepileptic: An agent that combats epilepsy. [EU] Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antimycotic: Suppressing the growth of fungi. [EU] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are
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split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antithrombotic: Preventing or interfering with the formation of thrombi; an agent that so acts. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aortic Aneurysm: Aneurysm of the aorta. [NIH] Aphakia: Absence of crystalline lens totally or partially from field of vision, from any cause except after cataract extraction. Aphakia is mainly congenital or as result of lens dislocation and subluxation. [NIH] Aponeurosis: Tendinous expansion consisting of a fibrous or membranous sheath which serves as a fascia to enclose or bind a group of muscles. [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] 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] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH]
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Aromatic: Having a spicy odour. [EU] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Articular: Of or pertaining to a joint. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aseptic: Free from infection or septic material; sterile. [EU] Aspartate: A synthetic amino acid. [NIH] Aspartic: The naturally occurring substance is L-aspartic acid. One of the acidic-amino-acids is obtained by the hydrolysis of proteins. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] 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] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements.
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This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atopic allergy: A person with a type I allergic reaction, specifically with strong familiar tendencies, caused by allergens such as pollens, foods, etc. [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] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [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] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autologous bone marrow transplantation: A procedure in which bone marrow is removed from a person, stored, and then given back to the person after intensive treatment. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Auxin: A natural organic compound formed in actively growing parts of plants, particularly in the growing points of shoots, which in minute concentrations regulates cell expansion and other developmental processes. [NIH] Avian: A plasmodial infection in birds. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron
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cell body. [NIH] Azaserine: Antibiotic substance produced by various Streptomyces species. It is an inhibitor of enzymatic activities that involve glutamine and is used as an antineoplastic and immunosuppressive agent. [NIH] Bacteremia: The presence of viable bacteria circulating in the blood. Fever, chills, tachycardia, and tachypnea are common acute manifestations of bacteremia. The majority of cases are seen in already hospitalized patients, most of whom have underlying diseases or procedures which render their bloodstreams susceptible to invasion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterial Translocation: The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basal metabolic rate: Represents the minimum energy expenditure required for the maintenance of vital functions; normally the amount of energy expended, measured in calories, per unit of time at rest; measured after 14-18 hours of rest. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH]
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Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
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] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Beta carotene: A vitamin A precursor. Beta carotene belongs to the family of fat-soluble vitamins called carotenoids. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Beta-sheet: Two or more parallel or anti-parallel strands are arranged in rows. [NIH] Beta-Thromboglobulin: A platelet-specific protein which is released when platelets aggregate. Elevated plasma levels have been reported after deep venous thrombosis, preeclampsia, myocardial infarction with mural thrombosis, and myeloproliferative disorders. Measurement of beta-thromboglobulin in biological fluids by radioimmunoassay is used for the diagnosis and assessment of progress of thromboembolic disorders. [NIH] Bifidobacterium: A rod-shaped, gram-positive, non-acid-fast, non-spore-forming, nonmotile bacterium that is a genus of the family Actinomycetaceae. It inhabits the intestines and feces of humans as well as the human vagina. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bilateral cancer: Cancer that occurs in both paired organs, such as both breasts or both ovaries. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding agent: A substance that makes a loose mixture stick together. For example, binding agents can be used to make solid pills from loose powders. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioartificial Organs: Artificial organs that are composites of biomaterials and cells. The
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biomaterial can act as a membrane (container) as in bioartificial liver or a scaffold as in bioartificial skin. [NIH] Bioassays: Determination of the relative effective strength of a substance (as a vitamin, hormone, or drug) by comparing its effect on a test organism with that of a standard preparation. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [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] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [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] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [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]
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Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Coagulation Factors: Endogenous substances, usually proteins, that are involved in the blood coagulation process. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blotting and transferred to strips of nitrocellulose paper. The blots are then detected by radiolabeled antibody probes. [NIH] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Body Fluids: Liquid components of living organisms. [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] 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] 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
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permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bromelain: An enzyme found in pineapples that breaks down other proteins, such as collagen and muscle fiber, and has anti-inflammatory properties. It is used as a meat tenderizer in the food industry. [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] Bronchoalveolar Lavage: Washing out of the lungs with saline or mucolytic agents for diagnostic or therapeutic purposes. It is very useful in the diagnosis of diffuse pulmonary infiltrates in immunosuppressed patients. [NIH] 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] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]
Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Bypass: A surgical procedure in which the doctor creates a new pathway for the flow of body fluids. [NIH] Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease. [NIH] Cadaverine: A foul-smelling diamine formed by bacterial decarboxylation of lysine. [NIH] Cadmium: An element with atomic symbol Cd, atomic number 48, and atomic weight 114. It
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is a metal and ingestion will lead to cadmium poisoning. [NIH] Cadmium Poisoning: Poisoning occurring after exposure to cadmium compounds or fumes. It may cause gastrointestinal syndromes, anemia, or pneumonitis. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Pyrophosphate: Diphosphoric acid, calcium salt. An inorganic pyrophosphate which affects calcium metabolism in mammals. Abnormalities in its metabolism occur in some human diseases, notably hypophosphatasia and pseudogout. [NIH] Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA topoisomerase. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity. [NIH] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
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Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxy-terminal: The end of any polypeptide or protein that bears a free carboxyl group. [NIH]
Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiotonic: 1. Having a tonic effect on the heart. 2. An agent that has a tonic effect on the heart. [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] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin)
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and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catalyse: To speed up a chemical reaction. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] 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] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by gluten-containing foods. The intestinal mucosa shows loss of villous structure. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [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 Fusion: Fusion of somatic cells in vitro or in vivo, which results in somatic cell hybridization. [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]
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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] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellular metabolism: The sum of all chemical changes that take place in a cell through which energy and basic components are provided for essential processes, including the synthesis of new molecules and the breakdown and removal of others. [NIH] 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] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Arteries: The arteries supplying the cerebral cortex. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]
Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] 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
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vagina. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [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] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemical Warfare: Tactical warfare using incendiary mixtures, smokes, or irritant, burning, or asphyxiating gases. [NIH] Chemical Warfare Agents: Chemicals that are used to cause the disturbance, disease, or death of humans during war. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chlorine: A greenish-yellow, diatomic gas that is a member of the halogen family of elements. It has the atomic symbol Cl, atomic number 17, and atomic weight 70.906. It is a powerful irritant that can cause fatal pulmonary edema. Chlorine is used in manufacturing, as a reagent in synthetic chemistry, for water purification, and in the production of chlorinated lime, which is used in fabric bleaching. [NIH] Chlorophyll: Porphyrin derivatives containing magnesium that act to convert light energy in photosynthetic organisms. [NIH] Chloroplasts: Plant cell inclusion bodies that contain the photosynthetic pigment chlorophyll, which is associated with the membrane of thylakoids. Chloroplasts occur in cells of leaves and young stems of higher plants. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholera: An acute diarrheal disease endemic in India and Southeast Asia whose causative agent is vibrio cholerae. This condition can lead to severe dehydration in a matter of hours unless quickly treated. [NIH] Choleretic: A choleretic agent. [EU] 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]
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Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroid Plexus: A villous structure of tangled masses of blood vessels contained within the third, lateral, and fourth ventricles of the brain. It regulates part of the production and composition of cerebrospinal fluid. [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] Chromium: A trace element that plays a role in glucose metabolism. It has the atomic symbol Cr, atomic number 24, and atomic weight 52. According to the Fourth Annual Report on Carcinogens (NTP85-002,1985), chromium and some of its compounds have been listed as known carcinogens. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic 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] Chymopapain: A cysteine endopeptidase isolated from papaya latex. Preferential cleavage at glutamic and aspartic acid residues. EC 3.4.22.6. [NIH] Chymotrypsin: A serine endopeptidase secreted by the pancreas as its zymogen, chymotrypsinogen and carried in the pancreatic juice to the duodenum where it is activated by trypsin. It selectively cleaves aromatic amino acids on the carboxyl side. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Claviceps: A genus of ascomycetous fungi, family Clavicipitaceae, order Hypocreales,
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parasitic on various grasses. The sclerotia contain several toxic alkaloids. Claviceps purpurea on rye causes ergotism. [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] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clot Retraction: Retraction of a clot resulting from contraction of platelet pseudopods attached to fibrin strands that is dependent on the contractile protein thrombosthenin. Used as a measure of platelet function. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Cobalt: A trace element that is a component of vitamin B12. It has the atomic symbol Co, atomic number 27, and atomic weight 58.93. It is used in nuclear weapons, alloys, and pigments. Deficiency in animals leads to anemia; its excess in humans can lead to erythrocytosis. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cod Liver Oil: Oil obtained from fresh livers of the cod family, Gadidae. It is a source of vitamins A and D. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] 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]
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Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Colorectal Cancer: Cancer that occurs in the colon (large intestine) or the rectum (the end of the large intestine). A number of digestive diseases may increase a person's risk of colorectal cancer, including polyposis and Zollinger-Ellison Syndrome. [NIH] Comatose: Pertaining to or affected with coma. [EU] 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]
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Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Conjunctivitis: Inflammation of the conjunctiva, generally consisting of conjunctival hyperaemia associated with a discharge. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue Cells: A group of cells that includes fibroblasts, cartilage cells, adipocytes, smooth muscle cells, and bone cells. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is
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represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuous infusion: The administration of a fluid into a blood vessel, usually over a prolonged period of time. [NIH] 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] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [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] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the
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internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroids: Hormones that have antitumor activity in lymphomas and lymphoid leukemias; in addition, corticosteroids (steroids) may be used for hormone replacement and for the management of some of the complications of cancer and its treatment. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Coumarin: A fluorescent dye. [NIH] Coumestrol: A coumarin derivative occurring naturally in forage crops which has estrogenic activity. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Critical Illness: A disease or state in which death is possible or imminent. [NIH] Crystallins: A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. The presence of these proteins accounts for the transparency of the lens. The family is composed of four major groups, alpha, beta, gamma, and delta, and several minor groups, which are classed on the basis of size, charge, immunological properties, and vertebrate source. Alpha, beta, and delta crystallins occur in avian and reptilian lenses, while alpha, beta, and gamma crystallins occur in all other lenses. [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] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanobacteria: A subgroup of the oxygenic photosynthetic bacteria comprised of unicellular to multicellular photosynthetic bacteria possessing chlorophyll a and carrying out oxygenic photosynthesis. Cyanobacteria are the only known organisms capable of fixing
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both carbon dioxide (in the presence of light) and nitrogen. Formerly called blue-green algae, cyanobacteria were traditionally treated as algae. By the late 19th century, however, it was realized that the blue-green algae were unique and lacked the traditional nucleus and chloroplasts of the green and other algae. The comparison of nucleotide base sequence data from 16S and 5S rRNA indicates that cyanobacteria represent a moderately deep phylogenetic unit within the gram-negative bacteria. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclin: Molecule that regulates the cell cycle. [NIH] Cyclin A: A 33-kD protein identical to adenovirus E1A-associated protein p60. Cyclin A regulates p33cdk2 and p34cdc2, and is necessary for progression through the S phase of the cell cycle. [NIH] Cyclophosphamide: Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the liver to form the active aldophosphamide. It is used in the treatment of lymphomas, leukemias, etc. Its side effect, alopecia, has been made use of in defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH]
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Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Decongestant: An agent that reduces congestion or swelling. [EU] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Defense Mechanisms: Unconscious process used by an individual or a group of individuals in order to cope with impulses, feelings or ideas which are not acceptable at their conscious level; various types include reaction formation, projection and self reversal. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delivery of Health Care: The concept concerned with all aspects of providing and distributing health services to a patient population. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the
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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] Dermal: Pertaining to or coming from the skin. [NIH] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] 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] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developing Countries: Countries in the process of change directed toward economic growth, that is, an increase in production, per capita consumption, and income. The process of economic growth involves better utilization of natural and human resources, which results in a change in the social, political, and economic structures. [NIH] Developmental psychology: That branch of psychology which studies the processes of preand post-natal growth and the maturation of behavior. In its broadest sense, developmental psychology includes the periods of infancy, childhood, and adulthood. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [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] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the
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abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Dietary Proteins: Proteins obtained from foods. They are the main source of the essential amino acids. [NIH] Dietetics: The study and regulation of the diet. [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] Dihydrotestosterone: Anabolic agent. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH] Dilatation: The act of dilating. [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] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dipeptides: Peptides composed of two amino acid units. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] 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
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in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] 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 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] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-limiting: Describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Costs: The amount that a health care institution or organization pays for its drugs. It is one component of the final price that is charged to the consumer (fees, pharmaceutical or prescription fees). [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] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges)
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covering the brain and spinal cord; called also pachymeninx. [EU] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrocoagulation: Electrosurgical procedures used to treat hemorrhage (e.g., bleeding ulcers) and to ablate tumors, mucosal lesions, and refractory arrhythmias. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the treatment of severe affective disorders and schizophrenia. [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]
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Electroretinography: Recording of electric potentials in the retina after stimulation by light. [NIH]
Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [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] Empyema: Presence of pus in a hollow organ or body cavity. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocarditis: Exudative and proliferative inflammatory alterations of the endocardium, characterized by the presence of vegetations on the surface of the endocardium or in the endocardium itself, and most commonly involving a heart valve, but sometimes affecting the inner lining of the cardiac chambers or the endocardium elsewhere. It may occur as a primary disorder or as a complication of or in association with another disease. [EU] Endocardium: The innermost layer of the heart, comprised of endothelial cells. [NIH] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [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.
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[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] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium, Lymphatic: Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. [NIH] Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components from interstitium to lumen; this function has been most intensively studied in the blood capillaries. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Enteral Nutrition: Nutritional support given via the alimentary canal or any route connected to the gastrointestinal system (i.e., the enteral route). This includes oral feeding, sip feeding, and tube feeding using nasogastric, gastrostomy, and jejunostomy tubes. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Enteritis: Inflammation of the intestine, applied chiefly to inflammation of the small intestine; see also enterocolitis. [EU] Enterocolitis: Inflammation of the intestinal mucosa of the small and large bowel. [NIH] Enterocytes: Terminally differentiated cells comprising the majority of the external surface of the intestinal epithelium (see intestinal mucosa). Unlike goblet cells, they do not produce or secrete mucins, nor do they secrete cryptdins as do the paneth cells. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing
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radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Eosinophilia: Abnormal increase in eosinophils in the blood, tissues or organs. [NIH] Eosinophilic: A condition found primarily in grinding workers caused by a reaction of the pulmonary tissue, in particular the eosinophilic cells, to dust that has entered the lung. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] 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] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Epitope: A molecule or portion of a molecule capable of binding to the combining site of an antibody. For every given antigenic determinant, the body can construct a variety of antibody-combining sites, some of which fit almost perfectly, and others which barely fit. [NIH]
Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH]
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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 Perforation: A dilated vessel in the lower end of the esophagus that result from portal hypertension. [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] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen receptor: ER. Protein found on some cancer cells to which estrogen will attach. [NIH]
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] Ethionine: 2-Amino-4-(ethylthio)butyric acid. An antimetabolite and methionine antagonist that interferes with amino acid incorporation into proteins and with cellular ATP utilization. It also produces liver neoplasms. [NIH] Ethylene Glycol: A colorless, odorless, viscous dihydroxy alcohol. It has a sweet taste, but is poisonous if ingested. Ethylene glycol is the most important glycol commercially available and is manufactured on a large scale in the United States. It is used as an antifreeze and coolant, in hydraulic fluids, and in the manufacture of low-freezing dynamites and resins. [NIH]
Etoposide: A semisynthetic derivative of podophyllotoxin that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] Excisional: The surgical procedure of removing a tumor by cutting it out. The biopsy is then examined under a microscope. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of
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energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]
External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciculation: A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibres innervated by a single motor nerve filament. [EU]
Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue
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development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fermentation: An enzyme-induced chemical change in organic compounds that takes place in the absence of oxygen. The change usually results in the production of ethanol or lactic acid, and the production of energy. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibril: Most bacterial viruses have a hollow tail with specialized fibrils at its tip. The tail fibers attach to the cell wall of the host. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fistulas: An abnormal passage from one hollow structure of the body to another, or from a hollow structure to the surface, formed by an abscess, disease process, incomplete closure of a wound, or by a congenital anomaly. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in
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carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatulence: Production or presence of gas in the gastrointestinal tract which may be expelled through the anus. [NIH] Flatus: Gas passed through the rectum. [NIH] Flexor: Muscles which flex a joint. [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] Fluorouracil: A pyrimidine analog that acts as an antineoplastic antimetabolite and also has immunosuppressant. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]
Fovea: The central part of the macula that provides the sharpest vision. [NIH] Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fructose: A type of sugar found in many fruits and vegetables and in honey. Fructose is used to sweeten some diet foods. It is considered a nutritive sweetener because it has
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calories. [NIH] Fucose: Deoxysugar. [NIH] Fulminant Hepatic Failure: Liver failure that occurs suddenly in a previously healthy person. The most common causes of FHF are acute hepatitis, acetaminophen overdose, and liver damage from prescription drugs. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungus: A general term used to denote a group of eukaryotic protists, including mushrooms, yeasts, rusts, moulds, smuts, etc., which are characterized by the absence of chlorophyll and by the presence of a rigid cell wall composed of chitin, mannans, and sometimes cellulose. They are usually of simple morphological form or show some reversible cellular specialization, such as the formation of pseudoparenchymatous tissue in the fruiting body of a mushroom. The dimorphic fungi grow, according to environmental conditions, as moulds or yeasts. [EU] Gadolinium: An element of the rare earth family of metals. It has the atomic symbol Gd, atomic number 64, and atomic weight 157.25. Its oxide is used in the control rods of some nuclear reactors. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gallium: A rare, metallic element designated by the symbol, Ga, atomic number 31, and atomic weight 69.72. [NIH] Gamma Oryzanol: The frequency of activity bursts ranging from 20 to 90 hertz, this term is used in analogy with a range of high-frequency X-rays. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-Glutamyltransferase: An enzyme that catalyzes reversibly the transfer of a glutamyl group from a glutamyl-peptide and an amino acid to a peptide and a glutamylamino acid. EC 2.3.2.2. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH]
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Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]
Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrointestinal Transit: Passage of food (sometimes in the form of a test meal) through the gastrointestinal tract as measured in minutes or hours. The rate of passage through the intestine is an indicator of small bowel function. [NIH] Gastrostomy: Creation of an artificial external opening into the stomach for nutritional support or gastrointestinal compression. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] 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 Targeting: The integration of exogenous DNA into the genome of an organism at sites where its expression can be suitably controlled. This integration occurs as a result of homologous recombination. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [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]
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Genital: Pertaining to the genitalia. [EU] Genitourinary: Pertaining to the genital and urinary organs; urogenital; urinosexual. [EU] 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] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Gliadin: Simple protein, one of the prolamines, derived from the gluten of wheat, rye, etc. May be separated into 4 discrete electrophoretic fractions. It is the toxic factor associated with celiac disease. [NIH] Glial Fibrillary Acidic Protein: An intermediate filament protein found only in glial cells or cells of glial origin. MW 51,000. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] 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] 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
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and water to D-glucose and orthophosphate. EC 3.1.3.9. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamate Dehydrogenase: An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2. [NIH] Glutamate Synthase: An enzyme that catalyzes the formation of 2 molecules of glutamate from glutamine plus alpha-ketoglutarate in the presence of NADPH. EC 1.4.1.13. [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] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
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] 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] Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Glycoside: Any compound that contains a carbohydrate molecule (sugar), particularly any such natural product in plants, convertible, by hydrolytic cleavage, into sugar and a nonsugar component (aglycone), and named specifically for the sugar contained, as glucoside (glucose), pentoside (pentose), fructoside (fructose) etc. [EU] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Goblet Cells: Cells of the epithelial lining that produce and secrete mucins. [NIH]
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Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonorrhea: Acute infectious disease characterized by primary invasion of the urogenital tract. The etiologic agent, Neisseria gonorrhoeae, was isolated by Neisser in 1879. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method. [NIH] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Gram-Positive Cocci: Coccus-shaped bacteria that retain the crystal violet stain when treated by Gram's method. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH]
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Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Haemorrhage: The escape of blood from the vessels; bleeding. Small haemorrhages are classified according to size as petechiae (very small), purpura (up to 1 cm), and ecchymoses (larger). The massive accumulation of blood within a tissue is called a haematoma. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Care Costs: The actual costs of providing services related to the delivery of health care, including the costs of procedures, therapies, and medications. It is differentiated from health expenditures, which refers to the amount of money paid for the services, and from fees, which refers to the amount charged, regardless of cost. [NIH] Health Expenditures: The amounts spent by individuals, groups, nations, or private or public organizations for total health care and/or its various components. These amounts may or may not be equivalent to the actual costs (health care costs) and may or may not be shared among the patient, insurers, and/or employers. [NIH] 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] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels
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of 9 percent or more. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatic Veins: Veins which drain the liver. [NIH] Hepatic Veno-Occlusive Disease: Blockage of the small- or medium-sized hepatic veins due to nonthrombotic subendothelial edema which may progress to fibrosis. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatoblastoma: A type of liver tumor that occurs in infants and children. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatoma: A liver tumor. [NIH] Herbicides: Pesticides used to destroy unwanted vegetation, especially various types of weeds, grasses, and woody plants. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Zoster: Acute vesicular inflammation. [NIH] Herpetiformis: Duhring's disease a recurring, inflammatory disease of the skin of unknown etiology characterized by erythematous, papular, pustular, or vesicular lesions which tend to group and are accompanied by itching and burning. [NIH] Heterodimers: Zippered pair of nonidentical proteins. [NIH]
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Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Hobbies: Leisure activities engaged in for pleasure. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Horny layer: The superficial layer of the epidermis containing keratinized cells. [NIH] Hospital Charges: The prices a hospital sets for its services. Hospital costs (the direct and indirect expenses incurred by the hospital in providing the services) are one factor in the determination of hospital charges. Other factors may include, for example, profits, competition, and the necessity of recouping the costs of uncompensated care. [NIH] Hospital Costs: The expenses incurred by a hospital in providing care. The hospital costs attributed to a particular patient care episode include the direct costs plus an appropriate proportion of the overhead for administration, personnel, building maintenance, equipment, etc. Hospital costs are one of the factors which determine hospital charges (the price the hospital sets for its services). [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [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]
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Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other 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] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] 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] Hyperaemia: An excess of blood in a part; engorgement. [EU] Hyperammonemia: Metabolic disorder characterized by elevated level of ammonia in blood. [NIH] Hyperbaric: Characterized by greater than normal pressure or weight; applied to gases under greater than atmospheric pressure, as hyperbaric oxygen, or to a solution of greater specific gravity than another taken as a standard of reference. [EU] Hyperbaric oxygen: Oxygen that is at an atmospheric pressure higher than the pressure at sea level. Breathing hyperbaric oxygen to enhance the effectiveness of radiation therapy is being studied. [NIH] Hyperglycaemia: Abnormally increased content of sugar in the blood. [EU] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperoxia: An abnormal increase in the amount of oxygen in the tissues and organs. [NIH]
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Hypersecretion: Excessive secretion. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]
Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileal: Related to the ileum, the lowest end of the small intestine. [NIH] Ileostomy: Surgical creation of an external opening into the ileum for fecal diversion or drainage. Loop or tube procedures are most often employed. [NIH] Ileum: The lower end of the small intestine. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoblotting: Immunologic methods for isolating and quantitatively measuring immunoreactive substances. When used with immune reagents such as monoclonal antibodies, the process is known generically as western blot analysis (blotting, western).
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[NIH]
Immunocompromised: Having a weakened immune system caused by certain diseases or treatments. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In 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] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Nutrition: Nutrition of children from birth to 2 years of age. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus,
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or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infectious Diarrhea: Diarrhea caused by infection from bacteria, viruses, or parasites. [NIH] 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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Integrins:
A
family
of
transmembrane
glycoproteins
consisting
of
noncovalent
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heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Intensive Care: Advanced and highly specialized care provided to medical or surgical patients whose conditions are life-threatening and require comprehensive care and constant monitoring. It is usually administered in specially equipped units of a health care facility. [NIH]
Intensive Care Units: Hospital units providing continuous surveillance and care to acutely ill patients. [NIH] Interleukin-4: Soluble factor produced by activated T-lymphocytes that causes proliferation and differentiation of B-cells. Interleukin-4 induces the expression of class II major histocompatibility complex and Fc receptors on B-cells. It also acts on T-lymphocytes, mast cell lines, and several other hematopoietic lineage cells including granulocyte, megakaryocyte, and erythroid precursors, as well as macrophages. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Interleukin-8: A cytokine that activates neutrophils and attracts neutrophils and Tlymphocytes. It is released by several cell types including monocytes, macrophages, Tlymphocytes, fibroblasts, endothelial cells, and keratinocytes by an inflammatory stimulus. IL-8 is a member of the beta-thromboglobulin superfamily and structurally related to platelet factor 4. [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] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intrahepatic: Within the liver. [NIH] Intramuscular: IM. Within or into muscle. [NIH]
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Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Transport: The movement of ions across energy-transducing cell membranes. Transport can be active or passive. Passive ion transport (facilitated diffusion) derives its energy from the concentration gradient of the ion itself and allows the transport of a single solute in one direction (uniport). Active ion transport is usually coupled to an energy-yielding chemical or photochemical reaction such as ATP hydrolysis. This form of primary active transport is called an ion pump. Secondary active transport utilizes the voltage and ion gradients produced by the primary transport to drive the cotransport of other ions or molecules. These may be transported in the same (symport) or opposite (antiport) direction. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irinotecan: An anticancer drug that belongs to a family of anticancer drugs called topoisomerase inhibitors. It is a camptothecin analogue. Also called CPT 11. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] 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] Isoflavones: 3-Phenylchromones. Isomeric form of flavones in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. [NIH] Isoleucine: An essential branched-chain amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and
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energy levels. [NIH] Isometric Contraction: Muscular contractions characterized by increase in tension without change in length. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jejunostomy: Surgical formation of an opening through the abdominal wall into the jejunum, usually for enteral hyperalimentation. [NIH] Jejunum: That portion of the small intestine which extends from the duodenum to the ileum; called also intestinum jejunum. [EU] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kainate: Glutamate receptor. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keratinocytes: Epidermal cells which synthesize keratin and undergo characteristic changes as they move upward from the basal layers of the epidermis to the cornified (horny) layer of the skin. Successive stages of differentiation of the keratinocytes forming the epidermal layers are basal cell, spinous or prickle cell, and the granular cell. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] 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] Ketonuria: Having ketone bodies in the urine; a warning sign of diabetic ketoacidosis (DKA). [NIH] Ketosis: A condition of having ketone bodies build up in body tissues and fluids. The signs of ketosis are nausea, vomiting, and stomach pain. Ketosis can lead to ketoacidosis. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney
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failure, chronic) is irreversible and requires hemodialysis. [NIH] Kinesin: A microtubule-associated mechanical adenosine triphosphatase, that uses the energy of ATP hydrolysis to move organelles along microtubules toward the plus end of the microtubule. The protein is found in squid axoplasm, optic lobes, and in bovine brain. Bovine kinesin is a heterotetramer composed of two heavy (120 kDa) and two light (62 kDa) chains. EC 3.6.1.-. [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] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lactation: The period of the secretion of milk. [EU] Lactobacillus: A genus of gram-positive, microaerophilic, rod-shaped bacteria occurring widely in nature. Its species are also part of the many normal flora of the mouth, intestinal tract, and vagina of many mammals, including humans. Pathogenicity from this genus is rare. [NIH] Lactobacillus acidophilus: A species of gram-positive, rod-shaped bacteria isolated from the intestinal tract of humans and animals, the human mouth, and vagina. This organism produces the fermented product, acidophilus milk. [NIH] Lactoperoxidase: An enzyme derived from cow's milk. It catalyzes the radioiodination of tyrosine and its derivatives and of peptides containing tyrosine. [NIH] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
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] Leishmaniasis: A disease caused by any of a number of species of protozoa in the genus Leishmania. There are four major clinical types of this infection: cutaneous (Old and New World), diffuse cutaneous, mucocutaneous, and visceral leishmaniasis. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] 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]
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Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
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] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Libido: The psychic drive or energy associated with sexual instinct in the broad sense (pleasure and love-object seeking). It may also connote the psychic energy associated with instincts in general that motivate behavior. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lice: A general name for small, wingless, parasitic insects, previously of the order Phthiraptera. Though exact taxonomy is still controversial, they can be grouped in the orders Anoplura (sucking lice), Mallophaga (biting lice), and Rhynchophthirina (elephant lice). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Life Cycle Stages: The continuous sequence of changes undergone by metamorphosing insects and other animals during the post-embryonic development process. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] 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] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH]
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Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [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]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Neoplasms: Tumors or cancer of the liver. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [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] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH]
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Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphokines: Soluble protein factors generated by activated lymphocytes that affect other cells, primarily those involved in cellular immunity. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macronutrients: Nutrients in the diet that are the key sources of energy, namely protein, fat, and carbohydrates. [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] Magnesium Chloride: Magnesium chloride. An inorganic compound consisting of one magnesium and two chloride ions. The compound is used in medicine as a source of magnesium ions, which are essential for many cellular activities. It has also been used as a cathartic and in alloys. [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] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malaria: A protozoan disease caused in humans by four species of the genus Plasmodium (P. falciparum (malaria, falciparum), P. vivax (malaria, vivax), P. ovale, and P. malariae) and transmitted by the bite of an infected female mosquito of the genus Anopheles. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high fever, sweating, shaking chills, and anemia. Malaria in animals is caused by other species of plasmodia. [NIH] Malaria, Falciparum: Malaria caused by Plasmodium falciparum. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations. [NIH] Malaria, Vivax: Malaria caused by Plasmodium vivax. This form of malaria is less severe than malaria, falciparum, but there is a higher probability for relapses to occur. Febrile paroxysms often occur every other day. [NIH] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH]
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Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammary: Pertaining to the mamma, or breast. [EU] Mammogram: An x-ray of the breast. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Mannans: Polysaccharides consisting of mannose units. [NIH] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. [NIH] Mastitis: Inflammatory disease of the breast, or mammary gland. [NIH] Maximum Tolerated Dose: The highest dose level eliciting signs of toxicity without having major effects on survival relative to the test in which it is used. [NIH] Meat: The edible portions of any animal used for food including domestic mammals (the major ones being cattle, swine, and sheep) along with poultry, fish, shellfish, and game. [NIH]
Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] 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] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [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] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH]
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Melibiose: A disaccharide consisting of one galactose and one glucose moiety in an alpha (1-6) glycosidic linkage. [NIH] Melphalan: An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen. [NIH] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Potentials: Ratio of inside versus outside concentration of potassium, sodium, chloride and other ions in diffusible tissues or cells. Also called transmembrane and resting potentials, they are measured by recording electrophysiologic responses in voltagedependent ionic channels of (e.g.) nerve, muscle and blood cells as well as artificial membranes. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Menopause: Permanent cessation of menstruation. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaplasia: A condition in which there is a change of one adult cell type to another similar adult cell type. [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] Methicillin Resistance: Non-susceptibility of a microbe to the action of methicillin, a semisynthetic penicillin derivative. [NIH]
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Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] 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] Micronutrients: Essential dietary elements or organic compounds that are required in only small quantities for normal physiologic processes to occur. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Middle Cerebral Artery: The largest and most complex of the cerebral arteries. Branches of the middle cerebral artery supply the insular region, motor and premotor areas, and large regions of the association cortex. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitogen-Activated Protein Kinase Kinases: A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate mitogen-activated protein kinases and are themselves phosphorylated by MAP kinase kinase kinases. JNK kinases (also known as SAPK kinases) are a subfamily. EC 2.7.10.- [NIH] Mitogen-Activated Protein Kinases: A superfamily of protein-serine-threonine kinases that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by mitogen-activated protein kinase kinases which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP kinase
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kinase kinases). Families of these mitogen-activated protein kinases (MAPKs) include extracellular signal-regulated kinases (ERKs), stress-activated protein kinases (SAPKs) (also known as c-jun terminal kinases (JNKs)), and p38-mitogen-activated protein kinases. EC 2,7,1.- [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] 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] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] Molecular mass: The sum of the atomic masses of all atoms in a molecule, based on a scale in which the atomic masses of hydrogen, carbon, nitrogen, and oxygen are 1, 12, 14, and 16, respectively. For example, the molecular mass of water, which has two atoms of hydrogen and one atom of oxygen, is 18 (i.e., 2 + 16). [NIH] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] 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]
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Monomethylhydrazine: Hydrazine substituted by one methyl group. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monophosphate: So called second messenger for neurotransmitters and hormones. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Neurons: Neurons which activate muscle cells. [NIH] Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucocutaneous: Pertaining to or affecting the mucous membrane and the skin. [EU] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucosal Lining: The lining of GI tract organs that makes mucus. [NIH] Mucositis: A complication of some cancer therapies in which the lining of the digestive system becomes inflamed. Often seen as sores in the mouth. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multiple Organ Failure: A progressive condition usually characterized by combined failure of several organs such as the lungs, liver, kidney, along with some clotting mechanisms, usually postinjury or postoperative. [NIH] Multiple Trauma: Physical insults or injuries occurring simultaneously in several parts of the body. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Hypertonia: Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging,
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reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts. [NIH]
Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing myocardial reperfusion injury. [NIH] Myocardial Reperfusion Injury: Functional, metabolic, or structural changes in ischemic heart muscle thought to result from reperfusion to the ischemic areas. Changes can be fatal to muscle cells and may include edema with explosive cell swelling and disintegration, sarcolemma disruption, fragmentation of mitochondria, contraction band necrosis, enzyme washout, and calcium overload. Other damage may include hemorrhage and ventricular arrhythmias. One possible mechanism of damage is thought to be oxygen free radicals. Treatment currently includes the introduction of scavengers of oxygen free radicals, and injury is thought to be prevented by warm blood cardioplegic infusion prior to reperfusion. [NIH]
Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopia: That error of refraction in which rays of light entering the eye parallel to the optic
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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 fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nasogastric: The process of passing a small, flexible plastic tube through the nose or mouth into the stomach or small intestine. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] 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] Necrotizing Enterocolitis: A condition in which part of the tissue in the intestines is destroyed. Occurs mainly in under-weight newborn babies. A temporary ileostomy may be necessary. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nelfinavir: A potent HIV protease inhibitor. It is used in combination with other antiviral drugs in the treatment of HIV in both adults and children. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatologist: Doctor who specializes in treating the diseases and disorders of newborn babies. [NIH] Neonatology: A subspecialty of pediatrics concerned with the newborn infant. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU]
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Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [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 Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurites: In tissue culture, hairlike projections of neurons stimulated by growth factors and other molecules. These projections may go on to form a branched tree of dendrites or a single axon or they may be reabsorbed at a later stage of development. "Neurite" may refer to any filamentous or pointed outgrowth of an embryonal or tissue-culture neural cell. [NIH] Neuroblastoma: Cancer that arises in immature nerve cells and affects mostly infants and children. [NIH] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts 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] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
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Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] 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] Neutrophil: A type of white blood cell. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [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] Nitrogenase: An enzyme system that catalyzes the fixing of nitrogen in soil bacteria and blue-green algae (cyanobacteria). EC 1.18.6.1. [NIH] Nociceptors: Peripheral receptors for pain. Nociceptors include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli. All nociceptors are free nerve endings. [NIH] Nodose: Having nodes or projections. [EU] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] N-terminal: Peptide of the area containing the NH2 group. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]
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Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleolus: A small dense body (sub organelle) within the nucleus of eukaryotic cells, visible by phase contrast and interference microscopy in live cells throughout interphase. Contains RNA and protein and is the site of synthesis of ribosomal RNA. [NIH] Nucleosomes: The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. This core is composed of the histones H2A, H2B, H3, and H4. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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] Nutritive Value: An indication of the contribution of a food to the nutrient content of the diet. This value depends on the quantity of a food which is digested and absorbed and the amounts of the essential nutrients (protein, fat, carbohydrate, minerals, vitamins) which it contains. This value can be affected by soil and growing conditions, handling and storage, and processing. [NIH] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] 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] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] Oncology: The study of cancer. [NIH] Oncorhynchus: A genus of the family Salmonidae (salmons and trouts). They are named for their hooked (onco) nose (rhynchus). They are usually anadromous and occasionally inhabit freshwater. They can be found in North Pacific coastal areas from Japan to California and adjacent parts of the Arctic Ocean. Salmon and trout are popular game and food fish. Various species figure heavily in genetic, metabolism, and hormone research. [NIH]
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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] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic cup: The white, cup-like area in the center of the optic disc. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Ornithine Carbamoyltransferase: A urea cycle enzyme that catalyzes the formation of orthophosphate and L-citrulline from carbamoyl phosphate and L-ornithine. Deficiency of this enzyme may be transmitted as an X-linked trait. EC 2.1.3.3. [NIH] Osmolality: The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per kilogram of solvent. The osmolality is directly proportional to the colligative properties of solutions; osmotic pressure, boiling point elevation, freezing point depression, and vapour pressure lowering. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmoles: The standard unit of osmotic pressure. [NIH] Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a
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solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] 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] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] 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] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxaliplatin: An anticancer drug that belongs to the family of drugs called platinum compounds. [NIH] Oxaloacetate: An anionic form of oxaloacetic acid. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]
Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxidative metabolism: A chemical process in which oxygen is used to make energy from carbohydrates (sugars). Also known as aerobic respiration, cell respiration, or aerobic
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metabolism. [NIH] Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palmitic Acid: A common saturated fatty acid found in fats and waxes including olive oil, palm oil, and body lipids. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [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] Paneth Cells: Epithelial cells found in the basal part of the intestinal glands (crypts of Lieberkuhn). Paneth cells synthesize and secrete lysozyme and cryptdins. [NIH] Papain: A proteolytic enzyme obtained from Carica papaya. It is also the name used for a purified mixture of papain and chymopapain that is used as a topical enzymatic debriding agent. EC 3.4.22.2. [NIH]
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Papillomavirus: A genus of Papovaviridae causing proliferation of the epithelium, which may lead to malignancy. A wide range of animals are infected including humans, chimpanzees, cattle, rabbits, dogs, and horses. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
Parasite: An animal or a plant that lives on or in an organism of another species and gets at least some of its nutrition from that other organism. [NIH] Parasitic: Having to do with or being a parasite. A parasite is an animal or a plant that lives on or in an organism of another species and gets at least some of its nutrients from it. [NIH] 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] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [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]
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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] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] Petrolatum: A colloidal system of semisolid hydrocarbons obtained from petroleum. It is used as an ointment base, topical protectant, and lubricant. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Phallic: Pertaining to the phallus, or penis. [EU]
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Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenolphthalein: An acid-base indicator which is colorless in acid solution, but turns pink to red as the solution becomes alkaline. It is used medicinally as a cathartic. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylacetate: A drug being studied in the treatment of cancer. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylbutyrate: An anticancer drug that belongs to the family of drugs called differentiating agents. [NIH] Phenylephrine: An alpha-adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] 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 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] Photocoagulation: Using a special strong beam of light (laser) to seal off bleeding blood vessels such as in the eye. The laser can also burn away blood vessels that should not have grown in the eye. This is the main treatment for diabetic retinopathy. [NIH]
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Photosensitivity: An abnormal cutaneous response involving the interaction between photosensitizing substances and sunlight or filtered or artificial light at wavelengths of 280400 mm. There are two main types : photoallergy and photoxicity. [EU] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmapheresis: Procedure whereby plasma is separated and extracted from anticoagulated whole blood and the red cells retransfused to the donor. Plasmapheresis is also employed for therapeutic use. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of
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molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Platinum Compounds: Inorganic compounds which contain platinum as the central atom. [NIH]
Pleura: The thin serous membrane enveloping the lungs and lining the thoracic cavity. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Podophyllotoxin: The main active constituent of the resin from the roots of may apple or mandrake (Podophyllum peltatum and P. emodi). It is a potent spindle poison, toxic if taken internally, and has been used as a cathartic. It is very irritating to skin and mucous membranes, has keratolytic actions, has been used to treat warts and keratoses, and may have antineoplastic properties, as do some of its congeners and derivatives. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH]
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Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] 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] 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] Polyposis: The development of numerous polyps (growths that protrude from a mucous membrane). [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Population Growth: Increase, over a specific period of time, in the number of individuals living in a country or region. [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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-synaptic: 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] Post-traumatic: Occurring as a result of or after injury. [EU] 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] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH]
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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] Precancerous: A term used to describe a condition that may (or is likely to) become cancer. Also called premalignant. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premalignant: A term used to describe a condition that may (or is likely to) become cancer. Also called precancerous. [NIH] Prescription Fees: The charge levied on the consumer for drugs or therapy prescribed under written order of a physician or other health professional. [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] Prickle: Several layers of the epidermis where the individual cells are connected by cell bridges. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Probenecid: The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy. [NIH] Proctocolectomy: An operation to remove the colon and rectum. Also called coloproctectomy. [NIH] Profusion: Profusion is the number of small rounded opacities per unit area, that is, per zone. [NIH] Progeny: The offspring produced in any generation. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH]
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Prognostic factor: A situation or condition, or a characteristic of a patient, that can be used to estimate the chance of recovery from a disease, or the chance of the disease recurring (coming back). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Promotor: In an operon, a nucleotide sequence located at the operator end which contains all the signals for the correct initiation of genetic transcription by the RNA polymerase holoenzyme and determines the maximal rate of RNA synthesis. [NIH] 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] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] Prostaglandin: Any of a group of components derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway that are extremely potent mediators of a diverse group of physiologic processes. The abbreviation for prostaglandin is PG; specific compounds are designated by adding one of the letters A through I to indicate the type of substituents found on the hydrocarbon skeleton and a subscript (1, 2 or 3) to indicate the number of double bonds in the hydrocarbon skeleton e.g., PGE2. The predominant naturally occurring prostaglandins all have two double bonds and are synthesized from arachidonic acid (5,8,11,14-eicosatetraenoic acid) by the pathway shown in the illustration. The 1 series and 3 series are produced by the same pathway with fatty acids having one fewer double bond (8,11,14-eicosatrienoic acid or one more double bond (5,8,11,14,17-eicosapentaenoic acid) than arachidonic acid. The subscript a or ß indicates the configuration at C-9 (a denotes a substituent below the plane of the ring, ß, above the plane). The naturally occurring PGF's have the a configuration, e.g., PGF2a. All of the prostaglandins act by binding to specific cell-surface receptors causing an increase in the level of the intracellular second messenger cyclic AMP (and in some cases cyclic GMP also). The effect produced by the cyclic AMP increase depends on the specific cell type. In some cases there is also a positive feedback effect. Increased cyclic AMP increases prostaglandin synthesis leading to further increases in cyclic AMP. [EU] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins E: (11 alpha,13E,15S)-11,15-Dihydroxy-9-oxoprost-13-en-1-oic acid (PGE(1)); (5Z,11 alpha,13E,15S)-11,15-dihydroxy-9-oxoprosta-5,13-dien-1-oic acid (PGE(2)); and (5Z,11 alpha,13E,15S,17Z)-11,15-dihydroxy-9-oxoprosta-5,13,17-trien-1-oic acid (PGE(3)). Three of the six naturally occurring prostaglandins. They are considered primary in that no one is derived from another in living organisms. Originally isolated from sheep seminal fluid and vesicles, they are found in many organs and tissues and play a major role in mediating
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various physiological activities. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Folding: A rapid biochemical reaction involved in the formation of proteins. It begins even before a protein has been completely synthesized and proceeds through discrete intermediates (primary, secondary, and tertiary structures) before the final structure (quaternary structure) is developed. [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Transport: The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors. EC 2.7.10. [NIH] 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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [NIH]
Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that
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promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [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]
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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] 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]
Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Purpura: Purplish or brownish red discoloration, easily visible through the epidermis, caused by hemorrhage into the tissues. [NIH] Pustular: Pertaining to or of the nature of a pustule; consisting of pustules (= a visible collection of pus within or beneath the epidermis). [EU] Putrefaction: The process of decomposition of animal and vegetable matter by living organisms. [NIH] Putrescine: A toxic diamine formed by putrefaction from the decarboxylation of arginine and ornithine. [NIH] Pyridoxal: 3-Hydroxy-5-(hydroxymethyl)-2-methyl-4- pyridinecarboxaldehyde. [NIH] Pyrophosphatases: A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-. [NIH] Pyruvate Carboxylase: A biotin-dependent enzyme belonging to the ligase family that catalyzes the addition of carbon dioxide to pyruvate. It is occurs in both plants and animals. Deficiency of this enzyme causes severe psychomotor retardation and lactic acidosis in infants. EC 6.4.1.1. [NIH] Pyruvate Dehydrogenase Complex: An organized assembly of three kinds of enzymes; catalyzes the oxidative decarboxylation of pyruvate. [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] Quantitative Structure-Activity Relationship: A quantitative prediction of the biological, ecotoxicological or pharmaceutical activity of a molecule. It is based upon structure and activity information gathered from a series of similar compounds. [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]
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Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] 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] 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] Raffinose: A trisaccharide occurring in Australian manna (from Eucalyptus spp, Myrtaceae) and in cottonseed meal. [NIH] Rana pipiens: A highly variable species of the family Ranidae in Canada, the United States and Central America. It is the most widely used Anuran in biomedical research. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptivity: The condition of the reproductive organs of a female flower that permits effective pollination. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptor Aggregation: Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector 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]
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Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] 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] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rehydration: The restoration of water or of fluid content to a body or to substance which has become dehydrated. [EU] Rehydration Solutions: Fluids restored to the body in order to maintain normal waterelectrolyte balance. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal 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] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in
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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] Research Design: A plan for collecting and utilizing data so that desired information can be obtained with sufficient precision or so that an hypothesis can be tested properly. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [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] Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promotor and enhancer regions. [NIH]
Restitution: The restoration to a normal state. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Resuscitation: The restoration to life or consciousness of one apparently dead; it includes such measures as artificial respiration and cardiac massage. [EU] Retching: Dry vomiting. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour
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vision. Called also retinal, and retinene1. [EU] Retinal Detachment: Separation of the inner layers of the retina (neural retina) from the pigment epithelium. Retinal detachment occurs more commonly in men than in women, in eyes with degenerative myopia, in aging and in aphakia. It may occur after an uncomplicated cataract extraction, but it is seen more often if vitreous humor has been lost during surgery. (Dorland, 27th ed; Newell, Ophthalmology: Principles and Concepts, 7th ed, p310-12). [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoids: Derivatives of vitamin A. Used clinically in the treatment of severe cystic acne, psoriasis, and other disorders of keratinization. Their possible use in the prophylaxis and treatment of cancer is being actively explored. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhamnose: A methylpentose whose L- isomer is found naturally in many plant glycosides and some gram-negative bacterial lipopolysaccharides. [NIH] Rheumatoid: Resembling rheumatism. [EU] Riboflavin: Nutritional factor found in milk, eggs, malted barley, liver, kidney, heart, and leafy vegetables. The richest natural source is yeast. It occurs in the free form only in the retina of the eye, in whey, and in urine; its principal forms in tissues and cells are as FMN and FAD. [NIH] Ribonucleases: Enzymes that catalyze the hydrolysis of ester bonds within RNA. EC 3.1.-. [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] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Ristocetin: An antibiotic mixture of two components, A and B, obtained from Nocardia lurida (or the same substance produced by any other means). It is no longer used clinically because of its toxicity. It causes platelet agglutination and blood coagulation and is used to assay those functions in vitro. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rotavirus: A genus of Reoviridae, causing acute gastroenteritis in birds and mammals, including humans. Transmission is horizontal and by environmental contamination. [NIH] Rye: A hardy grain crop, Secale cereale, grown in northern climates. It is the most frequent
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host to ergot (claviceps), the toxic fungus. Its hybrid with wheat is triticale, another grain. [NIH]
Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saline: A solution of salt and water. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] Saturated fat: A type of fat found in greatest amounts in foods from animals, such as fatty cuts of meat, poultry with the skin, whole-milk dairy products, lard, and in some vegetable oils, including coconut, palm kernel, and palm oils. Saturated fat raises blood cholesterol more than anything else eaten. On a Step I Diet, no more than 8 to 10 percent of total calories should come from saturated fat, and in the Step II Diet, less than 7 percent of the day's total calories should come from saturated fat. [NIH] 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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in
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response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] 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] Sedentary: 1. Sitting habitually; of inactive habits. 2. Pertaining to a sitting posture. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Sella: A deep depression in the shape of a Turkish saddle in the upper surface of the body of the sphenoid bone in the deepest part of which is lodged the hypophysis cerebri. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Seminal fluid: Fluid from the prostate and other sex glands that helps transport sperm out of the man's body during orgasm. Seminal fluid contains sugar as an energy source for sperm. [NIH] Seminiferous tubule: Tube used to transport sperm made in the testes. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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
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and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serous: Having to do with serum, the clear liquid part of blood. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [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] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Sinusitis: An inflammatory process of the mucous membranes of the paranasal sinuses that occurs in three stages: acute, subacute, and chronic. Sinusitis results from any condition causing ostial obstruction or from pathophysiologic changes in the mucociliary transport mechanism. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]
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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] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [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]
Snake Venoms: Solutions or mixtures of toxic and nontoxic substances elaborated by snake (Ophidia) salivary glands for the purpose of killing prey or disabling predators and delivered by grooved or hollow fangs. They usually contain enzymes, toxins, and other factors. [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] Sodium Benzoate: The sodium salt of benzoic acid. It is used as an antifungal preservative in pharmaceutical preparations and foods. It may also be used as a test for liver function. [NIH]
Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] 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
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and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Species Specificity: Restriction of a characteristic or response to the members of one species; it usually refers to that property of the immune response which differentiates one species from another on the basis of antigen recognition, but the concept is not limited to immunology and is used loosely at levels higher than the species. [NIH] 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] Spectinomycin: An antibiotic produced by Streptomyces spectabilis. It is active against gram-negative bacteria and used for the treatment of gonorrhea. [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] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH] Spermidine: A polyamine formed from putrescine. It is found in almost all tissues in association with nucleic acids. It is found as a cation at all pH values, and is thought to help stabilize some membranes and nucleic acid structures. It is a precursor of spermine. [NIH] Spermine: A biogenic polyamine formed from spermidine. It is found in a wide variety of organisms and tissues and is an essential growth factor in some bacteria. It is found as a polycation at all pH values. Spermine is associated with nucleic acids, particularly in viruses, and is thought to stabilize the helical structure. [NIH] SPF: Sun protection factor, scale for rating the level of sunburn protection in sunscreen products. The higher the SPF, the more sunburn protection it provides. Sunscreens with an SPF value of 2 through 11 provide minimal protection against sunburns. Sunscreens with an SPF of 12 through 29 provide moderate protection, which is adequate for most people. Those with an SPF of 30 or higher provide high protection against sunburn and are sometimes recommended for people who are highly sensitive to the sun. [NIH] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [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]
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Spinous: Like a spine or thorn in shape; having spines. [NIH] Spleen: An organ that is part of the lymphatic system. The spleen produces lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Standard therapy: A currently accepted and widely used treatment for a certain type of cancer, based on the results of past research. [NIH] 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 cell transplantation: A method of replacing immature blood-forming cells that were destroyed by cancer treatment. The stem cells are given to the person after treatment to help the bone marrow recover and continue producing healthy blood cells. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Sterile: Unable to produce children. [NIH] Sterility: 1. The inability to produce offspring, i.e., the inability to conceive (female s.) or to induce conception (male s.). 2. The state of being aseptic, or free from microorganisms. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] 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.
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[EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Streptococci: A genus of spherical Gram-positive bacteria occurring in chains or pairs. They are widely distributed in nature, being important pathogens but often found as normal commensals in the mouth, skin, and intestine of humans and other animals. [NIH] Streptomycin: O-2-Deoxy-2-(methylamino)-alpha-L-glucopyranosyl-(1-2)-O-5- deoxy-3-Cformyl-alpha-L-lyxofuranosyl-(1-4)-N,N'-bis(aminoiminomethyl)-D-streptamine. Antibiotic substance produced by the soil actinomycete Streptomyces griseus. It acts by inhibiting the initiation and elongation processes during protein synthesis. [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] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stroke Volume: The amount of blood pumped out of the heart per beat not to be confused with cardiac output (volume/time). [NIH] Stroma: The middle, thickest layer of tissue in the cornea. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Sublingual: Located beneath the tongue. [EU] Submandibular: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Submaxillary: Four to six lymph glands, located between the lower jaw and the submandibular salivary gland. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] 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] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and
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methionine. [NIH] Sulfur Compounds: Inorganic or organic compounds that contain sulfur as an integral part of the molecule. [NIH] Sunburn: An injury to the skin causing erythema, tenderness, and sometimes blistering and resulting from excessive exposure to the sun. The reaction is produced by the ultraviolet radiation in sunlight. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
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] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific
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synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH] Synchrony: The normal physiologic sequencing of atrial and ventricular activation and contraction. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tachypnea: Rapid breathing. [NIH] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] 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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH]
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Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Thalassemia: A group of hereditary hemolytic anemias in which there is decreased synthesis of one or more hemoglobin polypeptide chains. There are several genetic types with clinical pictures ranging from barely detectable hematologic abnormality to severe and fatal anemia. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thiamine: 3-((4-Amino-2-methyl-5-pyrimidinyl)methyl)-5-(2methylthiazolium chloride. [NIH]
hydroxyethyl)-4-
Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] 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] 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]
Thrombophilia: A disorder of hemostasis in which there is a tendency for the occurrence of thrombosis. [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] Thymidine: A chemical compound found in DNA. Also used as treatment for mucositis. [NIH]
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Thymidylate Synthase: An enzyme of the transferase class that catalyzes the reaction 5,10methylenetetrahydrofolate and dUMP to dihydrofolate and dTMP in the synthesis of thymidine triphosphate. (From Dorland, 27th ed) EC 2.1.1.45. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [NIH] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Topoisomerase inhibitors: A family of anticancer drugs. The topoisomerase enzymes are responsible for the arrangement and rearrangement of DNA in the cell and for cell growth and replication. Inhibiting these enzymes may kill cancer cells or stop their growth. [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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH]
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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] Transaminase: Aminotransferase (= a subclass of enzymes of the transferase class that catalyse the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally 2-keto acid). Most of these enzymes are pyridoxal-phosphate-proteins. [EU]
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] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme "donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]
Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocating: The attachment of a fragment of one chromosome to a non-homologous chromosome. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Trifluoperazine: A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [NIH] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve
Dictionary 379
as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Trypan Blue: An azo that that is used in protozoal infections. [NIH] Trypanosomiasis: Infection with protozoa of the genus Trypanosoma. [NIH] Trypsin: A serine endopeptidase that is formed from trypsinogen in the pancreas. It is converted into its active form by enteropeptidase in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC 3.4.21.4. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tsetse Flies: Bloodsucking flies of the genus Glossina, found primarily in equatorial Africa. Several species are intermediate hosts of trypanosomes. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] 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] Tunicamycin: An N-acetylglycosamine containing antiviral antibiotic obtained from Streptomyces lysosuperificus. It is also active against some bacteria and fungi, because it inhibits the glucosylation of proteins. Tunicamycin is used as tool in the study of microbial biosynthetic mechanisms. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Typhimurium: Microbial assay which measures his-his+ reversion by chemicals which cause base substitutions or frameshift mutations in the genome of this organism. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] 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] Unsaturated Fats: A type of fat. [NIH]
380
Glutamine
Untranslated Regions: The parts of the messenger RNA sequence that do not code for product, i.e. the 5' untranslated regions and 3' untranslated regions. [NIH] Uracil: An anticancer drug that belongs to the family of drugs called alkylating agents. [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
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] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uricosuric: 1. Pertaining to, characterized by, or promoting uricosuria (= the excretion of uric acid in the urine). 2. An agent that promotes uricosuria. [EU] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urogenital: Pertaining to the urinary and genital apparatus; genitourinary. [EU] 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] 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] 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]
Vancomycin: Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to ristocetin that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear. [NIH] Vancomycin Resistance: Nonsusceptibility of bacteria, especially gram-positive cocci, to the action of vancomycin, an inhibitor of cell wall synthesis. [NIH]
Dictionary 381
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasopressor: 1. Stimulating contraction of the muscular tissue of the capillaries and arteries. 2. An agent that stimulates contraction of the muscular tissue of the capillaries and arteries. [EU]
Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [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] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vertigo: An illusion of movement; a sensation as if the external world were revolving around the patient (objective vertigo) or as if he himself were revolving in space (subjective vertigo). The term is sometimes erroneously used to mean any form of dizziness. [EU] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vibrio: A genus of Vibrionaceae, made up of short, slightly curved, motile, gram-negative rods. Various species produce cholera and other gastrointestinal disorders as well as abortion in sheep and cattle. [NIH] Vibrio cholerae: The etiologic agent of cholera. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Villous: Of a surface, covered with villi. [NIH] 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] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH]
382
Glutamine
Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of proteins, nucleic acids, and sometimes lipids, and their assembly into a new infectious particle. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Viscosity: A physical property of fluids that determines the internal resistance to shear forces. [EU] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [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] Vulgaris: An affection of the skin, especially of the face, the back and the chest, due to chronic inflammation of the sebaceous glands and the hair follicles. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] Wart: A raised growth on the surface of the skin or other organ. [NIH] Wasps: Any of numerous winged hymenopterous insects of social as well as solitary habits and having formidable stings. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the
Dictionary 383
cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xanthine: An urinary calculus. [NIH] Xanthophyll: A carotenoid alcohol widespread in nature. It is present in egg yolk, algae, and petals of yellow flowers, among other sources. [NIH] Xenobiotics: Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc. [NIH]
Xenograft: The cells of one species transplanted to another species. [NIH] Xeroderma Pigmentosum: A rare, pigmentary, and atrophic autosomal recessive disease affecting all races. It is manifested as an extreme photosensitivity to ultraviolet light as the result of a deficiency in the enzyme that permits excisional repair of ultraviolet-damaged DNA. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zinc Fingers: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
385
INDEX 3 3-dimensional, 31, 211, 281, 360 A Abdomen, 281, 294, 315, 332, 337, 351, 353, 372, 380, 382 Abdominal, 122, 163, 185, 223, 281, 282, 310, 321, 333, 334, 338, 340, 351, 353, 379 Abdominal Pain, 185, 281, 321, 338, 379 Aberrant, 13, 281 Ablation, 8, 281 Abscess, 281, 318 Acatalasia, 281, 298 Acceptor, 22, 56, 72, 281, 337, 350, 378 Acetaldehyde, 281, 284 Acetaminophen, 281, 320 Acetolactate Synthase, 240, 281 Acetone, 183, 281, 334 Acetylcholine, 281, 301, 347 Acetylcysteine, 110, 156, 281 Acetylglucosamine, 181, 281 Acidosis, 10, 40, 183, 208, 282, 309, 362 Actin, 217, 282, 344, 345, 379 Adaptability, 282, 298, 299 Adaptation, 3, 5, 22, 45, 143, 144, 156, 282, 300, 343, 356 Adenine, 224, 231, 282, 362 Adenocarcinoma, 124, 282, 326 Adenomatous Polyposis Coli, 96, 282 Adenosine, 19, 111, 157, 217, 282, 290, 296, 329, 335, 354, 376 Adenosine Monophosphate, 111, 157, 282 Adenovirus, 12, 282, 307 Adhesives, 235, 282 Adipocytes, 17, 23, 63, 154, 282, 304, 335 Adjustment, 282 Adjuvant, 226, 282, 321 Adolescence, 282, 352 Adrenal Cortex, 282, 306, 316, 358 Adrenal Medulla, 282, 315, 347 Adrenergic, 7, 208, 282, 288, 311, 315, 354, 374 Adrenergic Antagonists, 208, 282 Adsorption, 49, 283 Adsorptive, 283 Adverse Effect, 202, 283, 369 Aerobic, 30, 283, 341, 344, 350 Aerobic Metabolism, 30, 283, 351 Aerobic Respiration, 283, 350
Aerosol, 283, 374 Afferent, 51, 283, 317, 335, 358 Affinity, 10, 18, 46, 49, 50, 70, 77, 215, 230, 243, 244, 283, 289, 309, 370 Agar, 283, 306, 355 Age of Onset, 283, 295, 379 Agmatine, 182, 283 Agonist, 283, 311, 354 Airway, 206, 283 Alanine, 4, 21, 41, 61, 81, 107, 121, 143, 155, 176, 203, 243, 283 Albumin, 197, 284, 355 Alcohol Dehydrogenase, 218, 284 Aldehydes, 45, 284 Aldose Reductase Inhibitor, 246, 284 Algorithms, 284, 293 Alimentary, 91, 92, 139, 200, 284, 314, 352 Alkaline, 202, 203, 282, 284, 285, 296, 354 Alkalosis, 40, 284 Alkylating Agents, 284, 380 Alleles, 7, 284 Allergen, 206, 284, 309, 368 Allylamine, 284, 285 Alopecia, 284, 307 Alpha Particles, 284, 362 Alpha-1, 7, 284, 354 Alternative medicine, 250, 284 Alternative Splicing, 11, 285, 360 Alveoli, 285, 381 Amber, 44, 67, 77, 285 Amine, 182, 285, 327 Amino Acid Motifs, 285, 304 Amino Acid Sequence, 31, 78, 174, 193, 205, 221, 230, 251, 285, 287, 304, 317, 321 Ampulla, 285, 300, 314 Amylase, 187, 213, 285 Amyloid, 10, 13, 61, 81, 285 Anabaena, 65, 66, 67, 74, 136, 158, 285 Anabolic, 19, 120, 131, 285, 310 Anaesthesia, 285, 330 Anal, 286, 318 Analgesic, 281, 286, 302, 313, 336 Analog, 286, 309, 319 Analogous, 193, 216, 286, 357, 378 Anaphase, 46, 286 Anaphylatoxins, 286, 303 Anastomosis, 152, 286 Anatomical, 286, 290, 313, 330, 367
386
Glutamine
Anemia, 157, 171, 265, 270, 286, 296, 302, 319, 338, 376 Anesthesia, 283, 286, 334 Angiogenesis, 204, 286 Animal model, 20, 25, 53, 138, 286 Anionic, 286, 350 Anions, 284, 286, 333, 358, 369, 374 Aniridia, 183, 286 Anomalies, 190, 286, 343 Anterior chamber, 286, 333 Anterograde, 58, 286 Anthelmintic, 228, 286 Anthranilate Synthase, 78, 286 Anthropometry, 30, 286 Antibacterial, 178, 192, 287, 358, 371, 380 Antibiotic, 31, 69, 105, 174, 192, 200, 287, 291, 352, 366, 371, 373, 375, 379 Antibodies, 102, 136, 177, 181, 188, 196, 215, 237, 243, 287, 290, 325, 337, 342, 355, 363 Anticoagulant, 287, 360 Anticonvulsants, 38, 287 Antidiabetic, 207, 208, 287 Antiemetic, 287, 288, 300, 378 Antiepileptic, 28, 287 Antifungal, 177, 287, 370 Antigen, 16, 26, 68, 188, 243, 283, 287, 303, 327, 329, 330, 331, 332, 339, 368, 371 Antigen-Antibody Complex, 287, 303 Anti-infective, 176, 287, 328, 333 Anti-inflammatory, 281, 287, 289, 295, 309, 322, 330, 367 Anti-Inflammatory Agents, 287, 289 Antimetabolite, 287, 316, 319 Antimicrobial, 55, 86, 174, 238, 287, 309 Antimycotic, 178, 287 Antineoplastic, 232, 233, 284, 287, 291, 307, 319, 321, 340, 351, 356, 381 Antineoplastic Agents, 232, 233, 284, 287, 381 Antioxidant, 152, 191, 249, 287, 289, 350, 351 Antipsychotic, 288, 300, 378 Antiseptic, 281, 288 Antithrombotic, 174, 225, 288 Antitussive, 288, 309 Antiviral, 226, 281, 288, 345, 353, 379 Anus, 286, 288, 294, 319 Aorta, 288, 297, 305, 381 Aortic Aneurysm, 104, 288 Aphakia, 288, 366 Aponeurosis, 288, 320
Apoptosis, 6, 24, 47, 50, 59, 81, 91, 93, 96, 97, 129, 143, 244, 288, 298 Applicability, 55, 288 Aqueous, 222, 223, 232, 234, 235, 241, 288, 291, 307, 313, 328, 335 Arachidonic Acid, 288, 359 Aromatic, 289, 301, 354 Arterial, 284, 289, 299, 329, 360 Arteries, 288, 289, 294, 299, 305, 341, 344, 381 Arterioles, 289, 294, 344 Arteriolosclerosis, 289 Arteriosclerosis, 17, 289 Articular, 26, 182, 289, 350 Articulation, 289, 312 Ascites, 248, 289, 348 Ascorbic Acid, 289, 328 Aseptic, 289, 349, 372 Aspartate, 14, 28, 52, 89, 103, 109, 125, 130, 169, 190, 200, 230, 234, 289, 309, 334 Aspartic, 90, 180, 184, 193, 203, 232, 239, 243, 289, 301, 313 Aspartic Acid, 90, 180, 184, 193, 203, 232, 239, 243, 289, 301 Aspirin, 8, 289 Assay, 10, 23, 24, 50, 54, 69, 80, 101, 151, 210, 211, 237, 289, 329, 366, 379 Astrocytes, 28, 33, 44, 56, 85, 93, 125, 170, 289 Asymptomatic, 13, 30, 281, 289, 351 Ataxia, 117, 119, 123, 210, 242, 265, 289, 328, 376 Atmospheric Pressure, 290, 328 Atopic, 187, 188, 204, 205, 290 Atopic allergy, 188, 205, 290 ATP, 22, 24, 28, 120, 137, 146, 192, 228, 290, 306, 311, 316, 321, 323, 333, 335, 354, 360 Atrial, 24, 290, 375 Atrium, 290, 297, 381 Atrophy, 20, 34, 138, 175, 177, 209, 210, 242, 265, 290, 346 Attenuated, 290, 310 Atypical, 83, 196, 290 Auditory, 290, 358, 380 Autacoids, 290, 330 Autoantibodies, 215, 290 Autoantigens, 290 Autodigestion, 290, 351 Autoimmune disease, 290 Autoimmunity, 215, 290
Index 387
Autologous, 100, 110, 119, 157, 161, 207, 290 Autologous bone marrow transplantation, 110, 157, 290 Autonomic, 53, 281, 288, 290, 347, 353 Auxin, 240, 290 Avian, 50, 290, 306 Axons, 290, 308, 332, 349 Azaserine, 225, 230, 291 B Bacteremia, 192, 291 Bacterial Infections, 176, 226, 291, 299, 300 Bacterial Physiology, 282, 291 Bacterial Translocation, 96, 138, 147, 291 Bactericidal, 291, 316 Bacteriophage, 291, 355, 378 Bacterium, 31, 71, 221, 228, 291, 292, 326 Basal Ganglia, 288, 290, 291, 295, 320, 336, 343 Basal Ganglia Diseases, 290, 291, 343 Basal metabolic rate, 3, 291 Base Sequence, 291, 307, 319, 321 Basement Membrane, 291, 317, 335 Basophils, 188, 292, 324, 336 Benign, 20, 289, 292, 295, 320, 325, 345, 363 Benzene, 292, 333 Benzoic Acid, 292, 370 Beta carotene, 184, 292 Beta-pleated, 285, 292 Beta-sheet, 10, 292 Beta-Thromboglobulin, 292, 332 Bifidobacterium, 195, 292 Bilateral, 184, 292 Bilateral cancer, 184, 292 Bile, 25, 292, 320, 327, 337, 368, 372, 375 Bile Acids, 292, 372, 375 Bile Acids and Salts, 292 Bile Ducts, 292 Biliary, 25, 182, 238, 292, 300, 351 Biliary Tract, 292, 351 Bilirubin, 284, 292 Binding agent, 187, 214, 292 Binding Sites, 25, 27, 59, 292, 383 Bioartificial Organs, 238, 292 Bioassays, 197, 293 Bioavailability, 194, 293 Bioavailable, 214, 293 Biogenesis, 29, 55, 293 Biological therapy, 293, 324 Biological Transport, 293, 310 Biopsy, 207, 293, 316
Biosynthesis, 7, 22, 51, 59, 73, 75, 76, 124, 129, 137, 211, 228, 240, 281, 288, 293, 360, 369 Biotechnology, 60, 79, 102, 137, 250, 261, 263, 264, 265, 266, 293 Biotin, 196, 293, 362 Biotransformation, 293 Bismuth, 200, 293 Bladder, 8, 182, 293, 330, 360, 380 Blastocyst, 293, 304, 355 Blood Coagulation, 16, 294, 296, 366, 376 Blood Coagulation Factors, 294 Blood Glucose, 183, 185, 208, 294, 325, 329, 331 Blood Platelets, 294, 356, 369 Blood pressure, 51, 294, 297, 329, 342, 347, 370 Blood Volume, 175, 294 Blood-Brain Barrier, 8, 184, 294 Blot, 294, 329 Blotting, Western, 294, 329 Body Composition, 89, 122, 142, 161, 294 Body Fluids, 284, 294, 295, 311, 319, 348, 370 Bolus, 156, 294 Bolus infusion, 294 Bone Marrow Transplantation, 89, 98, 119, 141, 142, 146, 147, 148, 161, 294 Bowel Movement, 294, 310, 373 Brachytherapy, 294, 332, 362 Bradykinin, 294, 347, 355 Brain Neoplasms, 295, 328, 376 Brain Stem, 295, 299 Branch, 277, 295, 307, 309, 312, 337, 346, 352, 361, 371, 376 Breakdown, 5, 14, 175, 181, 202, 215, 295, 299, 309, 310, 320, 349, 354 Breeding, 187, 213, 217, 221, 295 Bromelain, 181, 295 Bronchi, 295, 315, 376, 378 Bronchial, 205, 295, 327, 376 Bronchoalveolar Lavage, 205, 295 Bronchopulmonary, 295, 365 Buccal, 295, 372 Buffers, 234, 295 Bulbar, 32, 34, 242, 295 Burns, 86, 122, 161, 164, 198, 214, 231, 295 Burns, Electric, 295 Butyric Acid, 28, 167, 181, 295, 316 Bypass, 22, 295, 344 C Cachexia, 199, 295
388
Glutamine
Cadaverine, 182, 295 Cadmium, 130, 295, 296 Cadmium Poisoning, 296 Caffeine, 296, 362 Calcification, 26, 289, 296 Calcium Channels, 123, 296 Calcium Pyrophosphate, 26, 296 Caloric intake, 53, 296 Calpain, 48, 296 Camptothecin, 296, 333 Cannabidiol, 296 Cannabinoids, 246, 296 Cannabinol, 296 Capsid, 73, 296, 382 Carbohydrate, 3, 118, 122, 139, 141, 160, 176, 179, 235, 247, 297, 322, 323, 348, 357 Carbon Dioxide, 193, 201, 297, 307, 308, 319, 320, 355, 362, 365 Carboxy, 114, 297 Carboxy-terminal, 114, 297 Carcinogen, 8, 297, 340 Carcinogenesis, 8, 184, 297 Carcinogenic, 284, 292, 297, 331, 348, 359, 372 Carcinoma, 112, 297 Cardiac, 24, 284, 296, 297, 313, 315, 316, 321, 344, 365, 372, 373 Cardiac Output, 24, 297, 373 Cardiopulmonary, 24, 297, 365 Cardiopulmonary Bypass, 24, 297 Cardiotonic, 297, 354 Cardiovascular, 7, 50, 54, 131, 225, 296, 297, 369 Cardiovascular disease, 225, 297 Carnitine, 110, 156, 184, 191, 234, 246, 297 Carotene, 292, 297, 365 Carotenoids, 292, 297 Carrier Proteins, 297, 355 Case report, 297, 302 Case series, 297, 302 Caspase, 32, 34, 81, 109, 298 Catabolism, 65, 68, 105, 124, 198, 298, 380 Catalase, 241, 281, 298 Catalyse, 298, 378 Catalytic Domain, 22, 230, 298 Cataract, 20, 29, 288, 298, 315, 366 Cathode, 298, 312 Cations, 153, 219, 298, 333 Caudal, 298, 310, 329, 357 Causal, 49, 298 Cause of Death, 31, 298 Celiac Disease, 251, 298, 322
Cell Adhesion, 27, 212, 298, 332 Cell Cycle, 9, 46, 52, 114, 204, 298, 301, 307, 316, 361 Cell Death, 6, 32, 34, 58, 59, 120, 197, 219, 288, 298, 316, 345 Cell Differentiation, 84, 206, 298, 369 Cell Division, 64, 216, 264, 286, 291, 298, 299, 307, 316, 324, 339, 342, 355, 359 Cell Fusion, 236, 298 Cell membrane, 293, 296, 297, 298, 309, 320, 333, 354 Cell proliferation, 6, 90, 94, 95, 143, 152, 289, 299, 369 Cell Respiration, 283, 299, 341, 350, 365 Cell Survival, 299, 324, 325 Cell Transplantation, 106, 211, 238, 299 Cellobiose, 299 Cellular metabolism, 228, 299 Cellulose, 187, 213, 299, 320, 355 Central Nervous System Infections, 299, 325, 328 Centrifugation, 299, 375 Cerebellar, 117, 197, 242, 290, 299, 364 Cerebellum, 38, 295, 299, 319, 364 Cerebral Arteries, 299, 341 Cerebral Infarction, 299, 328 Cerebrospinal, 86, 192, 299, 301, 328 Cerebrospinal fluid, 86, 192, 299, 301, 328 Cerebrovascular, 291, 297, 299, 347, 376 Cerebrum, 299, 379 Cervix, 138, 299 Chaperonins, 300, 342 Character, 300, 308, 323 Chelation, 246, 300 Chemical Warfare, 300, 308 Chemical Warfare Agents, 300, 308 Chemokines, 26, 300 Chemotactic Factors, 300, 303 Chemotherapy, 35, 52, 86, 113, 146, 148, 149, 152, 157, 158, 159, 166, 178, 199, 300 Chlorine, 184, 300 Chlorophyll, 69, 300, 306, 320 Chloroplasts, 300, 307 Chlorpromazine, 300, 378 Cholera, 175, 300, 381 Choleretic, 25, 300 Cholestasis, 25, 300 Cholesterol, 198, 292, 300, 305, 337, 367, 372 Choline, 184, 234, 301 Cholinergic, 51, 288, 301 Choroid, 9, 301, 365
Index 389
Choroid Plexus, 9, 301 Chromaffin System, 301, 313 Chromatin, 12, 288, 301, 348, 371 Chromium, 246, 301 Chromosomal, 301, 355, 367 Chromosome, 183, 301, 325, 336, 367, 378 Chronic, 10, 40, 55, 94, 177, 181, 186, 191, 209, 264, 295, 301, 314, 316, 331, 334, 351, 357, 369, 370, 373, 379, 380, 382 Chronic Disease, 177, 209, 295, 301 Chronic renal, 301, 357, 380 Chymopapain, 301, 351 Chymotrypsin, 64, 118, 301 Circulatory system, 301, 313 CIS, 45, 70, 101, 301, 365 Cisplatin, 35, 52, 133, 204, 301 Clamp, 32, 301 Claviceps, 301, 367 Clear cell carcinoma, 302, 309 Clinical Medicine, 157, 302, 358 Clinical study, 136, 302, 305 Clinical trial, 4, 33, 36, 171, 172, 261, 302, 305, 343, 361, 363 Cloning, 63, 64, 84, 137, 293, 302, 336 Clot Retraction, 302, 355 Coagulation, 224, 239, 294, 302, 326, 355, 376 Cobalt, 200, 203, 302 Cochlea, 302, 331 Cod Liver Oil, 302, 313 Codeine, 302, 309 Codon, 187, 204, 205, 210, 226, 302, 321 Coenzyme, 33, 191, 246, 289, 302 Cofactor, 37, 302, 360, 376 Colchicine, 302, 379 Colitis, 159, 303 Collagen, 26, 124, 282, 291, 295, 303, 318, 321, 356, 359 Collapse, 57, 295, 303 Colloidal, 200, 284, 303, 312, 353, 369, 374 Colorectal, 96, 129, 137, 138, 159, 164, 303 Colorectal Cancer, 159, 164, 303 Comatose, 218, 303 Complement, 55, 120, 179, 226, 233, 286, 303, 332, 338, 355, 368 Complementary and alternative medicine, 135, 168, 303 Complementary medicine, 135, 303 Complementation, 70, 304 Computational Biology, 261, 263, 304 Computed tomography, 196, 304 Computerized axial tomography, 304
Computerized tomography, 304 Conception, 304, 318, 372 Concomitant, 15, 211, 219, 304 Cones, 304, 365 Confusion, 304, 310, 380 Conjugated, 131, 159, 292, 304, 307 Conjunctiva, 304 Conjunctivitis, 192, 304 Connective Tissue, 26, 164, 289, 294, 303, 304, 318, 320, 321, 337, 340, 360 Connective Tissue Cells, 304 Consciousness, 286, 304, 308, 311, 326, 365 Consensus Sequence, 16, 285, 304, 305 Conserved Sequence, 285, 304 Constitutional, 183, 305 Constriction, 305, 333, 367 Consumption, 14, 178, 180, 222, 247, 305, 309, 321, 348, 351 Contamination, 305, 366 Continuous infusion, 35, 305 Contraindications, ii, 305 Controlled clinical trial, 24, 33, 122, 161, 305 Controlled study, 89, 110, 119, 140, 156, 161, 305 Conventional therapy, 175, 305 Conventional treatment, 305 Convulsions, 229, 305, 312 Convulsive, 229, 305 Coordination, 299, 305 Cornea, 286, 305, 323, 367, 373 Corneum, 43, 305, 315 Coronary, 24, 297, 305, 341, 344 Coronary Arteriosclerosis, 305, 344 Coronary Artery Bypass, 24, 305 Coronary heart disease, 297, 305 Coronary Thrombosis, 305, 341, 344 Cortex, 59, 103, 169, 290, 299, 305, 306, 314, 318, 341, 345, 358, 364 Cortical, 34, 36, 37, 48, 59, 196, 306, 317, 358, 368, 376 Corticosteroids, 306, 322 Cortisol, 50, 284, 306 Cortisone, 306, 309 Coumarin, 306 Coumestrol, 194, 306 Cranial, 299, 306, 317, 325, 332, 349, 352, 353, 380 Craniocerebral Trauma, 291, 306, 325, 328, 376, 377 Creatine, 33, 114, 122, 142, 161, 178, 235, 306
390
Glutamine
Creatine Kinase, 114, 235, 306 Creatinine, 89, 306, 380 Critical Illness, 24, 85, 117, 160, 198, 247, 306 Crystallins, 19, 29, 306 Crystallization, 13, 306 Culture Media, 197, 202, 283, 306 Curative, 306, 347, 376 Cutaneous, 13, 182, 306, 335, 355 Cyanobacteria, 61, 65, 68, 285, 306, 347 Cyclic, 32, 111, 157, 177, 296, 307, 324, 347, 359, 368, 376 Cyclin, 45, 46, 307 Cyclin A, 46, 307 Cyclophosphamide, 156, 166, 307 Cyst, 85, 128, 227, 307 Cystine, 184, 307 Cytochrome, 81, 131, 307, 351 Cytogenetics, 307, 367 Cytokine, 7, 14, 21, 96, 97, 103, 104, 107, 129, 307, 332 Cytoplasm, 48, 58, 288, 292, 298, 307, 312, 315, 324, 342, 344, 366, 375 Cytosine, 231, 307 Cytoskeletal Proteins, 296, 307 Cytoskeleton, 48, 58, 307, 332, 341 Cytotoxic, 23, 190, 226, 308, 363, 369 Cytotoxicity, 284, 301, 308 D Databases, Bibliographic, 261, 308 De novo, 19, 22, 33, 44, 45, 51, 117, 137, 211, 231, 308 Deamination, 177, 209, 308, 380 Decarboxylation, 295, 308, 327, 362 Decidua, 308, 355 Decongestant, 308, 354 Decontamination, 224, 308 Defense Mechanisms, 214, 308, 332 Degenerative, 34, 308, 326, 350, 366 Dehydration, 5, 175, 300, 308 Deletion, 27, 77, 183, 187, 204, 288, 308 Delivery of Health Care, 308, 325 Dementia, 196, 219, 237, 288, 308 Dendrites, 308, 346 Dendritic, 308, 339, 371 Density, 204, 212, 236, 299, 308, 337, 349 Dentate Gyrus, 308, 327 Deoxyribonucleic, 308, 366 Deoxyribonucleic acid, 308, 366 Depolarization, 309, 369 Depressive Disorder, 186, 309, 337
Deprivation, 54, 66, 91, 96, 98, 147, 161, 309 Dermal, 210, 309 DES, 80, 136, 286, 309 Desensitization, 17, 309 Detergents, 203, 309 Detoxification, 28, 309 Deuterium, 17, 309, 328 Developing Countries, 200, 309 Developmental psychology, 37, 309 Dexamethasone, 144, 238, 246, 309 Dextromethorphan, 190, 309 Diabetes Mellitus, 208, 245, 309, 322, 325 Diabetic Ketoacidosis, 309, 334 Diagnostic procedure, 173, 250, 309 Diaphragm, 309, 356 Diarrhea, 30, 106, 111, 146, 154, 164, 175, 185, 221, 310, 331, 338 Diarrhoea, 200, 310, 321 Diencephalon, 310, 329, 358, 376 Dietary Proteins, 14, 310 Dietetics, 248, 310 Dietitian, 251, 310 Diffusion, 38, 293, 310, 333 Digestion, 106, 185, 196, 247, 284, 292, 294, 310, 312, 332, 337, 372, 380 Digestive system, 172, 195, 217, 310, 343 Digestive tract, 182, 195, 310, 370, 372 Dihydrotestosterone, 310, 364 Dihydroxy, 178, 231, 310, 316, 359 Dilatation, 310, 358 Dilation, 294, 310, 328 Dilution, 185, 310, 315, 355 Dimerization, 10, 310 Dimethyl, 170, 246, 310 Dipeptides, 4, 175, 233, 310 Diploid, 304, 310, 355 Direct, iii, 16, 27, 30, 53, 58, 208, 217, 224, 229, 236, 246, 302, 310, 311, 327, 337, 364, 374 Disinfectant, 310, 316 Disorientation, 229, 304, 310 Dissociation, 235, 283, 310 Dissociative Disorders, 310, 311 Distal, 305, 311, 353, 361 Diuretic, 311, 339, 370 DNA Topoisomerase, 311, 321 Domesticated, 311, 324 Dopamine, 288, 300, 311, 354 Dorsal, 51, 212, 311, 357 Dorsum, 311, 320 Dose-limiting, 52, 311
Index 391
Drive, ii, vi, 9, 11, 40, 47, 127, 311, 333, 336 Drug Costs, 246, 311 Drug Interactions, 254, 311 Drug Tolerance, 311, 377 Duct, 285, 311, 317, 367 Duodenum, 51, 292, 301, 311, 314, 321, 334, 351, 368, 372 Dura mater, 311, 340, 351 Dyes, 285, 292, 312 Dysarthria, 242, 312 Dyspepsia, 200, 312 Dysphoric, 309, 312 Dysplasia, 265, 312 Dystrophy, 265, 312 E Edema, 82, 152, 312, 326, 332, 344, 348, 380 Effector, 52, 281, 303, 312, 347, 363 Effector cell, 312, 347, 363 Efficacy, 69, 105, 171, 175, 180, 185, 195, 242, 312, 337 Egg Yolk, 312, 383 Elasticity, 251, 289, 305, 312 Elastin, 303, 312 Elective, 24, 98, 104, 121, 149, 161, 312 Electrocoagulation, 302, 312 Electroconvulsive Therapy, 36, 90, 312 Electrolysis, 286, 298, 312 Electrolyte, 3, 175, 312, 319, 348, 357, 364, 370, 380 Electrons, 288, 291, 298, 312, 333, 338, 350, 362, 363 Electrophoresis, 19, 50, 312 Electrophysiological, 32, 312 Electroretinography, 6, 313 Elementary Particles, 312, 313, 338, 347, 361 Embryo, 293, 298, 312, 313, 330, 357 Emergency Treatment, 224, 313 Emollient, 313, 323 Empyema, 192, 313 Emulsion, 216, 313, 319 Enamel, 49, 313, 334 Encephalopathy, 11, 56, 118, 200, 313 Endemic, 300, 313, 338, 372 Endocarditis, 192, 313 Endocardium, 313 Endocrine Glands, 313 Endocrine System, 125, 313 Endocytosis, 118, 313 Endopeptidases, 313, 360 Endorphin, 184, 313 Endoscope, 314
Endoscopic, 35, 314 Endothelial cell, 8, 113, 294, 313, 314, 318, 332, 376 Endothelium, 8, 314, 347, 356 Endothelium, Lymphatic, 314 Endothelium, Vascular, 314 Endothelium-derived, 314, 347 Endotoxic, 314, 336 Endotoxin, 154, 314, 379 End-stage renal, 301, 314, 357 Energetic, 54, 314 Energy balance, 53, 314, 335 Enhancer, 314, 365 Enkephalin, 184, 314 Enteric Nervous System, 16, 314 Enteritis, 142, 175, 314 Enterocolitis, 314 Enterocytes, 22, 91, 145, 240, 314 Entorhinal Cortex, 314, 327 Environmental Exposure, 314, 348 Environmental Health, 45, 260, 262, 315 Enzymatic, 14, 26, 38, 45, 46, 54, 66, 109, 151, 241, 291, 296, 297, 298, 303, 315, 327, 351, 365 Enzyme Inhibitors, 315, 355 Eosinophil, 206, 315 Eosinophilia, 206, 315 Eosinophilic, 206, 315 Epidemic, 178, 315, 372 Epidermal, 5, 39, 40, 43, 92, 238, 315, 334, 339 Epidermal Growth Factor, 5, 238, 315 Epidermis, 39, 43, 305, 315, 327, 334, 358, 362 Epidermoid carcinoma, 315, 372 Epigastric, 315, 351 Epinephrine, 282, 283, 311, 315, 347, 379 Epithelial, 20, 40, 52, 91, 94, 97, 175, 282, 293, 308, 315, 323, 335, 351 Epithelial Cells, 20, 97, 175, 315, 335 Epithelium, 9, 291, 314, 315, 321, 333, 352, 366 Epitope, 244, 315 Ergot, 283, 315, 367 Erythrocyte Volume, 294, 315 Erythrocytes, 286, 294, 296, 315, 316, 364, 368 Esophageal, 35, 143, 248, 316 Esophageal Perforation, 248, 316 Esophageal Varices, 248, 316 Esophagitis, 199, 316 Esophagus, 310, 316, 372
392
Glutamine
Essential Tremor, 265, 316 Estradiol, 25, 194, 316 Estrogen, 25, 194, 316 Estrogen receptor, 194, 316 Ethanol, 7, 284, 316, 318 Ethionine, 230, 316 Ethylene Glycol, 180, 316 Etoposide, 51, 316 Eukaryotic Cells, 307, 316, 348, 349, 379 Evacuation, 316, 321, 335 Excisional, 316, 383 Excitability, 33, 316 Excitation, 193, 316 Excitatory, 28, 33, 41, 44, 193, 317, 323 Excitotoxicity, 6, 38, 197, 219, 317 Exhaustion, 317, 338 Exocrine, 50, 317, 351 Exogenous, 21, 283, 293, 317, 321, 379 Exon, 224, 285, 317 Extensor, 14, 317 External-beam radiation, 317, 362 Extracellular Matrix, 6, 27, 207, 213, 244, 304, 317, 318, 332 Extracellular Space, 40, 317 Extracorporeal, 238, 317 Extraction, 92, 288, 317, 366 Extravasation, 317, 325 Eye Infections, 282, 317 F Facial, 317, 352 Facial Nerve, 317, 352 Faecal, 310, 317 Family Planning, 261, 317 Fasciculation, 317, 346 Fatigue, 164, 181, 186, 317, 325 Fatty acids, 89, 182, 216, 248, 284, 309, 317, 359 Feces, 292, 317, 318, 373 Femoral, 297, 318 Femoral Artery, 297, 318 Fermentation, 63, 102, 221, 241, 284, 318 Fetus, 97, 129, 318, 355, 380 Fibril, 13, 27, 318 Fibrin, 16, 212, 294, 302, 318, 355, 376 Fibrinogen, 16, 212, 318, 355, 356, 376 Fibroblast Growth Factor, 83, 106, 318 Fibroblasts, 124, 210, 304, 318, 332 Fibronectin, 27, 60, 80, 111, 157, 212, 318 Fibrosis, 83, 206, 231, 248, 265, 284, 318, 326, 367 Filtration, 58, 318 Fissure, 308, 318, 358
Fistulas, 248, 318 Fixation, 75, 76, 193, 201, 318, 368 Flatulence, 185, 319 Flatus, 319, 320 Flexor, 317, 319 Fluid Therapy, 319, 348 Fluorescence, 19, 59, 319 Fluorouracil, 35, 110, 135, 166, 319 Folate, 199, 319 Fold, 55, 318, 319, 340 Folic Acid, 26, 196, 231, 319 Forearm, 294, 319 Fossa, 299, 319 Fourth Ventricle, 301, 319, 376 Fovea, 319 Fractionation, 319, 375 Frameshift, 319, 379 Frameshift Mutation, 319, 379 Frontal Lobe, 299, 319, 358 Fucose, 184, 320 Fulminant Hepatic Failure, 56, 320 Fungi, 178, 218, 287, 301, 317, 320, 324, 341, 379, 383 Fungus, 176, 178, 195, 315, 320, 367 G Gadolinium, 203, 320 Gallbladder, 281, 292, 310, 320 Gallium, 203, 320 Gamma Oryzanol, 181, 320 Gamma Rays, 320, 362, 363 Gamma-Glutamyltransferase, 24, 320 Ganglia, 51, 212, 281, 291, 314, 320, 346, 353 Ganglion, 6, 320, 349 Gap Junctions, 320, 374, 375 Gas, 23, 285, 297, 300, 310, 319, 320, 328, 338, 347, 373, 374, 381 Gas exchange, 320, 381 Gastric, 4, 20, 35, 51, 185, 200, 208, 225, 248, 290, 297, 315, 321, 327 Gastric Emptying, 4, 185, 208, 321 Gastric Juices, 185, 321 Gastric Mucosa, 21, 200, 321 Gastrin, 321, 327 Gastroenteritis, 321, 366 Gastrointestinal tract, 223, 247, 291, 316, 319, 321, 369, 370 Gastrointestinal Transit, 4, 321 Gastrostomy, 314, 321 Gelatin, 306, 321, 323, 376 Gels, 212, 321
Index 393
Gene Expression, 34, 35, 43, 51, 65, 97, 131, 159, 170, 197, 266, 321 Gene Targeting, 8, 321 Genetic Code, 47, 321, 348 Genetics, 33, 67, 81, 83, 101, 114, 117, 118, 120, 124, 137, 157, 183, 307, 321 Genistein, 194, 321 Genital, 302, 322, 380 Genitourinary, 183, 322, 380 Genotype, 7, 23, 322, 354 Germ Cells, 322, 339, 349, 350, 370, 371, 375 Gestation, 322, 353, 355 Ginkgo biloba, 246, 322 Ginseng, 178, 322 Gland, 282, 301, 306, 322, 337, 339, 351, 352, 355, 360, 367, 368, 372, 373, 377 Gliadin, 14, 251, 322 Glial Fibrillary Acidic Protein, 145, 322 Glomerular, 322, 339 Glomerular Filtration Rate, 322, 339 Glucocorticoid, 69, 93, 140, 309, 322 Gluconeogenesis, 10, 21, 28, 223, 239, 322 Glucose Intolerance, 309, 322 Glucose tolerance, 122, 208, 322 Glucose Tolerance Test, 322 Glucose-6-Phosphatase, 207, 208, 322 Glucuronic Acid, 323, 326 Glutamate Dehydrogenase, 6, 99, 125, 221, 323 Glutamate Synthase, 62, 323 Glutathione Peroxidase, 323, 368 Gluten, 13, 220, 221, 251, 298, 322, 323 Glycerol, 21, 39, 56, 77, 234, 295, 323, 354 Glycogen, 14, 54, 105, 207, 208, 323, 354 Glycolysis, 14, 30, 235, 323 Glycoprotein, 8, 318, 323, 324, 335, 343, 376, 379 Glycosaminoglycan, 239, 323 Glycoside, 195, 323, 367 Glycosidic, 231, 299, 323, 340, 354 Glycosylation, 17, 50, 97, 323 Goblet Cells, 314, 323 Gonad, 324 Gonadal, 183, 324, 372 Gonorrhea, 324, 371 Governing Board, 324, 358 Gp120, 10, 324, 353 Graft, 143, 324, 327, 330, 344 Graft Rejection, 324, 330 Grafting, 24, 305, 324, 330
Gram-negative, 291, 307, 314, 324, 366, 371, 381 Gram-Negative Bacteria, 307, 314, 324, 366, 371 Gram-positive, 292, 324, 335, 344, 373, 380 Gram-Positive Cocci, 324, 380 Granule, 197, 308, 324, 366 Granulocytes, 233, 324, 336, 369, 382 Grasses, 251, 302, 319, 324, 326 Growth, 3, 5, 19, 21, 23, 24, 27, 31, 47, 50, 52, 61, 65, 66, 68, 73, 75, 76, 83, 85, 89, 91, 92, 99, 105, 107, 112, 116, 118, 122, 138, 140, 143, 153, 154, 156, 165, 169, 175, 177, 180, 184, 185, 189, 193, 194, 197, 198, 200, 201, 202, 207, 209, 211, 212, 216, 220, 222, 224, 232, 236, 237, 238, 240, 241, 251, 265, 282, 286, 287, 288, 293, 298, 299, 306, 309, 315, 318, 324, 327, 331, 332, 339, 345, 346, 348, 349, 355, 361, 364, 368, 371, 377, 379, 380, 382 Growth factors, 5, 52, 197, 207, 232, 324, 346 Growth Substances, 240, 324 Guanylate Cyclase, 324, 347 Guinea Pigs, 68, 99, 324 H Habitat, 324, 344 Haematoma, 325 Haemorrhage, 147, 325 Hair follicles, 325, 382 Half-Life, 25, 325 Haploid, 325, 355 Haptens, 283, 325 Headache, 296, 325, 328 Health Care Costs, 16, 325 Health Expenditures, 325 Heart attack, 297, 325 Heart failure, 325, 348 Heat-Shock Proteins, 325, 342 Heat-Shock Proteins 90, 325, 342 Hematoma, 196, 325 Hematopoiesis, 12, 325 Heme, 8, 81, 292, 307, 325, 351 Hemoglobin, 286, 316, 325, 326, 333, 336, 376 Hemoglobinuria, 265, 326 Hemolytic, 326, 376 Hemorrhage, 306, 312, 325, 326, 344, 362, 373 Hemostasis, 326, 332, 369, 376 Heparin, 212, 232, 239, 326, 356
394
Glutamine
Hepatic, 6, 15, 23, 25, 28, 56, 81, 100, 131, 146, 207, 208, 229, 237, 238, 284, 322, 326 Hepatic Encephalopathy, 81, 326 Hepatic Veins, 326 Hepatic Veno-Occlusive Disease, 146, 326 Hepatitis, 73, 320, 326 Hepatoblastoma, 86, 326 Hepatocellular, 113, 326 Hepatocellular carcinoma, 113, 326 Hepatocyte, 7, 25, 73, 300, 326 Hepatoma, 91, 93, 108, 138, 326 Herbicides, 240, 326 Hereditary, 183, 225, 286, 326, 346, 353, 366, 376 Heredity, 321, 326 Herpes, 176, 326 Herpes Zoster, 326 Herpetiformis, 13, 326 Heterodimers, 326, 332 Heterogeneity, 69, 283, 327 Heterotrophic, 66, 320, 327 Hippocampus, 18, 38, 94, 107, 308, 327, 336, 373 Histamine, 190, 286, 288, 327 Histidine, 8, 19, 71, 176, 182, 184, 200, 203, 228, 231, 232, 235, 239, 327 Histology, 82, 327 Hobbies, 186, 327 Homeostasis, 15, 32, 53, 208, 234, 238, 327 Homogeneous, 54, 216, 289, 327 Homologous, 22, 55, 188, 284, 321, 327, 368, 374, 378 Hormonal, 18, 179, 208, 290, 327 Horny layer, 315, 327 Hospital Charges, 327 Hospital Costs, 144, 327 Host, 9, 24, 31, 74, 190, 191, 214, 218, 226, 227, 233, 235, 291, 318, 327, 329, 330, 367, 382 Housekeeping, 8, 327 Human growth hormone, 5, 85, 120, 131, 179, 198, 255, 327, 370 Humoral, 226, 324, 327 Humour, 327 Hybrid, 23, 46, 328, 367 Hybridization, 50, 298, 328 Hybridoma, 16, 137, 328 Hydrocephalus, 196, 328, 332 Hydrogen Peroxide, 195, 298, 323, 328, 337, 374 Hydrolysis, 56, 217, 289, 293, 299, 301, 328, 333, 335, 354, 357, 361, 362, 366, 379
Hydrophilic, 180, 309, 328 Hydrophobic, 61, 72, 78, 174, 309, 328, 337 Hydroxylysine, 303, 328 Hydroxyproline, 184, 303, 328 Hyperaemia, 304, 328 Hyperammonemia, 57, 328 Hyperbaric, 246, 328 Hyperbaric oxygen, 246, 328 Hyperglycaemia, 113, 328 Hyperglycemia, 17, 21, 154, 328 Hyperoxia, 104, 130, 328 Hypersecretion, 206, 329 Hypersensitivity, 284, 309, 315, 329, 368 Hypertension, 289, 297, 316, 329, 332, 380 Hypertrophy, 26, 329 Hypoglycemia, 21, 30, 329 Hypoglycemic, 30, 329 Hypotension, 288, 305, 329 Hypothalamic, 32, 130, 329 Hypothalamus, 32, 130, 195, 295, 310, 314, 329, 336, 355, 370, 376 Hypoxanthine, 231, 329 Hypoxia, 85, 162, 219, 329, 376 I Id, 132, 163, 264, 270, 271, 276, 278, 329 Ileal, 154, 329 Ileostomy, 329, 345 Ileum, 329, 334 Imaging procedures, 329, 378 Imidazole, 56, 77, 228, 293, 327, 329 Immune function, 90, 142, 178, 191, 231, 329 Immunity, 16, 80, 99, 105, 147, 189, 283, 329, 330, 338, 348 Immunization, 329, 330, 368 Immunoassay, 102, 196, 237, 329 Immunoblotting, 58, 329 Immunocompromised, 155, 178, 330 Immunodeficiency, 110, 156, 264, 330 Immunogenic, 226, 330, 336 Immunoglobulin, 10, 123, 287, 330, 342 Immunologic, 16, 104, 300, 329, 330, 363 Immunology, 12, 18, 97, 118, 161, 205, 282, 283, 330, 371 Immunosuppressant, 246, 284, 319, 330 Immunosuppressive, 291, 307, 322, 330 Immunosuppressive therapy, 330 Immunotherapy, 26, 293, 309, 330 Impairment, 58, 159, 191, 208, 219, 237, 289, 300, 317, 330, 340, 358 Implant radiation, 330, 332, 362 Implantation, 211, 304, 330
Index 395
In situ, 204, 330 Incontinence, 328, 330 Incubation, 45, 241, 330 Indicative, 242, 246, 330, 352, 381 Indomethacin, 139, 330 Induction, 26, 53, 106, 137, 162, 211, 288, 330, 334 Infancy, 309, 330 Infant Nutrition, 231, 330 Infarction, 299, 330, 364 Infectious Diarrhea, 270, 331 Inflammatory bowel disease, 113, 130, 248, 331 Infusion, 28, 81, 113, 123, 151, 331, 344 Ingestion, 122, 131, 162, 179, 188, 198, 200, 218, 296, 322, 331, 357 Inhalation, 188, 283, 331, 357 Initiation, 8, 20, 24, 47, 205, 331, 359, 373, 378 Initiator, 32, 331 Inlay, 331, 365 Inner ear, 51, 331, 380 Inorganic, 203, 235, 241, 296, 301, 331, 338, 343, 354, 356, 374 Inositol, 8, 39, 66, 73, 152, 331, 368 Insecticides, 331, 383 Insight, 11, 12, 40, 331 Insulin-dependent diabetes mellitus, 331 Insulin-like, 3, 85, 105, 107, 116, 154, 198, 331 Integrins, 16, 27, 244, 331 Intensive Care, 87, 99, 103, 106, 112, 124, 129, 144, 151, 332 Intensive Care Units, 124, 332 Interleukin-4, 205, 332 Interleukin-6, 83, 96, 106, 129, 332 Interleukin-8, 96, 129, 332 Intermittent, 85, 319, 332 Internal radiation, 332, 362 Interneurons, 33, 51, 332 Intoxication, 231, 332, 383 Intracranial Hemorrhages, 328, 332, 376 Intracranial Hypertension, 325, 328, 332, 377 Intrahepatic, 25, 332 Intramuscular, 150, 332, 352 Intraperitoneal, 229, 333 Intravascular, 239, 333 Intravenous, 4, 16, 80, 105, 123, 136, 140, 143, 175, 220, 331, 333, 352 Intrinsic, 12, 283, 291, 333 Invasive, 329, 333, 338
Involuntary, 291, 316, 333, 344, 364, 370, 371 Iodine, 44, 333 Ion Channels, 289, 333, 347, 375 Ion Transport, 66, 333 Ionizing, 284, 314, 333, 363 Ions, 54, 154, 234, 235, 291, 295, 296, 310, 312, 328, 333, 338, 340, 342, 361 Irinotecan, 146, 333 Iris, 183, 286, 305, 333 Ischemia, 8, 162, 219, 290, 333, 344, 364 Islet, 49, 333 Isoenzyme, 306, 333 Isoflavones, 194, 333 Isoleucine, 176, 182, 193, 198, 203, 233, 243, 281, 333 Isometric Contraction, 33, 334 Isozymes, 8, 334 J Jejunostomy, 314, 334 Jejunum, 5, 223, 334 Joint, 231, 289, 319, 334, 350, 374 K Kainate, 219, 310, 334 Kb, 11, 183, 260, 334 Keratin, 334, 367 Keratinocytes, 9, 39, 43, 332, 334 Ketamine, 190, 334 Keto, 44, 73, 182, 224, 241, 334, 378 Ketone Bodies, 28, 182, 183, 281, 309, 334 Ketonuria, 183, 334 Ketosis, 182, 208, 220, 309, 334 Kidney Disease, 172, 260, 265, 334 Kidney Failure, 314, 334, 339 Kinesin, 58, 335 Kinetic, 17, 36, 45, 54, 70, 106, 136, 160, 333, 335 L Labile, 303, 335 Labyrinth, 302, 331, 335, 368, 381 Lactation, 92, 231, 335 Lactobacillus, 72, 195, 335 Lactobacillus acidophilus, 195, 335 Lactoperoxidase, 174, 335 Laminin, 212, 291, 335 Large Intestine, 303, 310, 332, 335, 364, 370 Latent, 221, 335 Laxative, 283, 335, 371 Lectin, 90, 251, 335 Leishmaniasis, 218, 335 Lens, 19, 29, 288, 298, 306, 335, 365, 382 Leptin, 53, 335
396
Glutamine
Lesion, 25, 182, 305, 335, 337, 379 Lethal, 82, 120, 147, 291, 335 Lethargy, 328, 335 Leucine, 15, 23, 39, 49, 88, 176, 184, 188, 193, 198, 203, 233, 336 Leucocyte, 284, 315, 336 Leukemia, 71, 90, 264, 336 Leukocytes, 26, 292, 294, 300, 324, 330, 336, 342, 353, 379 Levo, 336, 340 Levorphanol, 309, 336 Libido, 180, 336 Library Services, 276, 336 Lice, 336 Life cycle, 19, 218, 320, 336 Life Cycle Stages, 218, 336 Ligament, 336, 360 Ligands, 16, 243, 332, 336 Ligase, 336, 362 Limbic, 336, 358 Limbic System, 336, 358 Linkage, 46, 64, 299, 336, 340 Lipid, 7, 43, 53, 140, 198, 240, 289, 301, 323, 331, 334, 336, 337, 351 Lipid A, 140, 336 Lipid Peroxidation, 198, 337, 351 Lipopolysaccharide, 141, 163, 324, 337 Lipoprotein, 324, 337, 382 Lithium, 185, 288, 337 Liver Neoplasms, 316, 337 Liver Transplantation, 56, 337 Lobe, 299, 327, 337 Localization, 44, 58, 87, 109, 169, 170, 183, 337 Localized, 15, 40, 120, 281, 318, 325, 331, 335, 337, 348, 355, 379 Locomotion, 337, 355 Long-Term Potentiation, 18, 337 Loop, 4, 5, 82, 329, 337 Lucida, 335, 337 Lymph, 291, 301, 314, 327, 337, 373 Lymph node, 291, 337 Lymphatic, 314, 331, 337, 340, 348, 370, 372 Lymphatic system, 337, 370, 372 Lymphocyte, 88, 103, 107, 120, 130, 140, 141, 150, 153, 287, 337, 338, 339 Lymphoid, 16, 287, 306, 336, 338 Lymphokines, 214, 338 Lymphoma, 251, 264, 338
Lysine, 62, 176, 179, 182, 184, 187, 193, 197, 198, 203, 213, 215, 232, 239, 295, 328, 338, 379 M Macronutrients, 4, 338 Macrophage, 154, 338 Magnesium Chloride, 235, 338 Magnetic Resonance Imaging, 338 Magnetic Resonance Spectroscopy, 24, 36, 338 Major Histocompatibility Complex, 226, 332, 338 Malabsorption, 248, 265, 298, 338, 369 Malabsorption syndrome, 338, 369 Malaria, 218, 226, 231, 338 Malaria, Falciparum, 338 Malaria, Vivax, 338 Malignancy, 26, 183, 338, 352 Malignant, 20, 184, 264, 282, 287, 289, 295, 339, 345, 363 Malnutrition, 4, 31, 221, 231, 284, 290, 295, 339, 344 Mammary, 305, 339 Mammogram, 296, 339, 341 Mania, 81, 339 Manic, 288, 337, 339 Mannans, 320, 339 Mannitol, 184, 235, 339 Mastitis, 220, 339 Maximum Tolerated Dose, 35, 311, 339 Meat, 131, 187, 213, 295, 339, 367 Medial, 289, 339, 349 Mediate, 18, 19, 25, 26, 37, 43, 244, 311, 339, 342 Mediator, 27, 40, 162, 244, 339, 356, 369 Medicament, 174, 218, 339 MEDLINE, 261, 263, 265, 339 Medullary, 309, 339 Megaloblastic, 319, 339 Meiosis, 339, 374 Melanin, 32, 333, 339, 354, 379 Melanocytes, 339 Melanoma, 264, 339 Melibiose, 184, 340 Melphalan, 110, 157, 340 Memantine, 246, 340 Membrane Potentials, 219, 340 Memory, 18, 90, 308, 337, 340 Meninges, 299, 306, 311, 340 Meningitis, 192, 340 Menopause, 340, 357 Mental Disorders, 172, 340, 361
Index 397
Mental Health, iv, 4, 172, 260, 262, 340, 361 Mental Processes, 310, 340, 361 Mental Retardation, 117, 183, 266, 340 Mesenchymal, 315, 340 Mesenteric, 88, 136, 139, 291, 340 Mesentery, 340 Metabolite, 76, 101, 194, 201, 293, 310, 340 Metaplasia, 20, 206, 340 Metastasis, 236, 244, 340 Metastatic, 78, 123, 159, 295, 340, 368 Methicillin Resistance, 78, 340 Methionine, 34, 62, 70, 76, 160, 184, 188, 190, 229, 310, 316, 341, 374 Methyltransferase, 78, 341 MI, 112, 150, 153, 154, 158, 279, 341 Microbe, 192, 340, 341, 377 Microbiological, 224, 228, 341 Microbiology, 18, 31, 50, 136, 282, 290, 341 Microcalcifications, 296, 341 Micronutrients, 198, 341 Microorganism, 302, 341, 352, 382 Micro-organism, 174, 341 Microscopy, 59, 291, 341, 348 Microtubules, 335, 341, 351 Middle Cerebral Artery, 8, 341 Migration, 14, 197, 213, 341 Mineralization, 251, 341 Mitochondria, 28, 58, 151, 234, 300, 341, 344, 349 Mitochondrial Swelling, 341, 345 Mitogen-Activated Protein Kinase Kinases, 341 Mitogen-Activated Protein Kinases, 92, 114, 341 Mitosis, 240, 288, 342 Mitotic, 46, 316, 342, 381 Mobilization, 5, 182, 342 Modeling, 6, 17, 29, 36, 342 Modification, 19, 29, 40, 51, 58, 66, 71, 118, 160, 186, 187, 211, 212, 213, 342, 362 Molecular Chaperones, 42, 55, 300, 325, 342 Molecular mass, 176, 178, 342 Molecular Structure, 194, 342 Monitor, 25, 50, 59, 306, 342, 347 Monoclonal, 16, 42, 215, 236, 243, 329, 342, 362 Monoclonal antibodies, 42, 215, 236, 243, 329, 342 Monocytes, 97, 100, 113, 120, 332, 336, 342 Monomethylhydrazine, 224, 343
Mononuclear, 96, 104, 136, 206, 342, 343, 379 Monophosphate, 56, 67, 217, 343 Morphological, 32, 57, 313, 320, 339, 343 Morphology, 3, 98, 147, 298, 343 Motility, 244, 330, 343, 369 Motion Sickness, 343, 345 Motor Activity, 305, 343 Motor Neurons, 34, 51, 343 Mucinous, 320, 343 Mucins, 314, 323, 343, 367 Mucociliary, 343, 369 Mucocutaneous, 335, 343 Mucolytic, 281, 295, 343 Mucosa, 4, 81, 91, 146, 156, 161, 177, 181, 209, 247, 291, 298, 314, 321, 343, 372 Mucosal Lining, 195, 343 Mucositis, 100, 110, 135, 157, 199, 343, 376 Mucus, 206, 343, 379 Multicenter Studies, 5, 343 Multicenter study, 87, 343 Multidrug resistance, 31, 35, 343 Multiple Organ Failure, 103, 343 Multiple Trauma, 107, 343 Muscle Fibers, 179, 343, 345, 378 Muscle Hypertonia, 343, 346 Muscular Atrophy, 32, 34, 210, 242, 265, 343 Muscular Dystrophies, 312, 344 Mutagenesis, 13, 19, 22, 160, 344 Mutagenic, 224, 284, 344 Mutagens, 319, 344 Mutate, 191, 344 Mycobacterium, 68, 69, 79, 99, 105, 243, 344, 379 Mydriatic, 310, 344, 354 Myeloma, 202, 328, 344 Myocardial infarction, 17, 292, 305, 341, 344 Myocardial Ischemia, 24, 344 Myocardial Reperfusion, 344, 365 Myocardial Reperfusion Injury, 344, 365 Myocardium, 341, 344 Myofibrils, 296, 344 Myopia, 344, 364, 366 Myosin, 27, 344, 345, 379 Myotonic Dystrophy, 265, 345 N Naive, 16, 345 Nasogastric, 314, 345 Natural selection, 293, 345 Nausea, 185, 287, 288, 321, 334, 345, 380
398
Glutamine
NCI, 1, 10, 172, 259, 301, 345 Necrosis, 96, 159, 288, 299, 330, 341, 344, 345, 364 Necrotizing Enterocolitis, 144, 162, 345 Nelfinavir, 106, 154, 345 Neocortex, 38, 345 Neonatal, 11, 22, 37, 82, 90, 102, 129, 141, 197, 345 Neonatologist, 37, 345 Neonatology, 11, 37, 345 Neoplasia, 264, 345 Neoplasm, 345, 379 Neoplastic, 338, 345 Nephropathy, 334, 345 Nephrosis, 346 Nephrotic, 184, 346 Nerve Endings, 169, 346, 347, 375 Nervous System, 44, 72, 193, 197, 218, 219, 229, 247, 265, 281, 283, 284, 292, 295, 296, 299, 320, 323, 339, 346, 349, 353, 369, 374, 375, 376 Neural, 34, 37, 51, 57, 84, 212, 283, 285, 327, 346, 366 Neurites, 212, 346 Neuroblastoma, 58, 82, 84, 105, 116, 346 Neurodegenerative Diseases, 10, 42, 68, 69, 84, 210, 219, 242, 247, 291, 346 Neurologic, 328, 346 Neurologist, 33, 346 Neuromuscular, 33, 34, 281, 346, 380 Neuromuscular Diseases, 33, 346 Neurons, 18, 30, 32, 33, 34, 37, 38, 41, 42, 44, 48, 51, 54, 58, 59, 67, 85, 125, 170, 182, 197, 219, 242, 308, 317, 320, 332, 343, 345, 346, 347, 374 Neuropathy, 245, 284, 346, 353 Neuropeptide, 16, 26, 32, 346 Neuropharmacology, 36, 346 Neurosecretory Systems, 313, 346 Neurotoxicity, 34, 56, 67, 117, 197, 230, 309, 346 Neurotoxin, 18, 56, 347 Neurotransmitters, 38, 190, 343, 346, 347 Neutralization, 206, 236, 347 Neutrons, 284, 347, 362 Neutrophil, 14, 90, 129, 141, 142, 347 Niacin, 90, 184, 196, 199, 231, 347, 379 Nimodipine, 246, 347 Nitric Oxide, 11, 57, 96, 129, 347 Nitrogenase, 65, 67, 75, 136, 347 Nociceptors, 182, 347 Nodose, 51, 347
Norepinephrine, 190, 282, 283, 311, 347 N-terminal, 29, 58, 81, 93, 109, 159, 188, 212, 226, 347 Nuclei, 29, 41, 243, 284, 312, 336, 338, 342, 347, 349, 361 Nucleic Acid Hybridization, 328, 348 Nucleolus, 348, 366 Nucleosomes, 12, 348 Nutritional Status, 30, 220, 348 Nutritional Support, 84, 103, 107, 148, 154, 248, 270, 321, 348 Nutritive Value, 174, 348 O Oedema, 235, 348 Oligopeptides, 175, 348 Oliguria, 334, 339, 348 Omega-3 fatty acid, 85, 137, 155, 348 Oncogene, 10, 170, 184, 264, 348 Oncogenic, 244, 332, 348, 361 Oncology, 110, 111, 139, 146, 151, 152, 199, 348 Oncorhynchus, 170, 348 Oocytes, 123, 190, 349 Opacity, 19, 298, 308, 349 Operon, 62, 63, 78, 349, 359, 365 Ophthalmology, 6, 83, 106, 319, 349, 366 Opportunistic Infections, 191, 349 Opsin, 349, 365 Optic Chiasm, 329, 349 Optic cup, 286, 349 Optic Nerve, 349, 351, 365, 367 Organ Culture, 14, 349, 377 Organelles, 234, 299, 307, 335, 339, 342, 349, 356 Ornithine, 15, 85, 89, 112, 115, 128, 137, 154, 167, 178, 182, 191, 198, 349, 362 Ornithine Carbamoyltransferase, 112, 137, 349 Osmolality, 236, 349 Osmolarity, 236, 339, 349 Osmoles, 349 Osmosis, 349 Osmotic, 77, 284, 341, 349, 369 Osteoarthritis, 26, 350 Osteoporosis, 208, 350 Otitis, 192, 350 Otitis Media, 192, 350 Outpatient, 5, 350 Ovaries, 292, 350 Ovary, 316, 324, 350, 357 Overdose, 320, 350 Overexpress, 201, 350
Index 399
Ovulation, 226, 227, 350 Ovum, 308, 322, 336, 350, 358 Oxaliplatin, 35, 350 Oxaloacetate, 28, 350 Oxidants, 45, 197, 241, 350 Oxidation, 21, 45, 53, 54, 111, 120, 128, 183, 241, 281, 288, 293, 307, 309, 323, 337, 350, 351 Oxidation-Reduction, 293, 350 Oxidative metabolism, 283, 350 Oxidative Phosphorylation, 53, 235, 351 Oxidative Stress, 56, 59, 95, 191, 351 Oxygen Consumption, 234, 351, 365 Oxygenase, 65, 81, 351 Oxygenation, 30, 351 Oxygenator, 297, 351 P Pachymeningitis, 340, 351 Paclitaxel, 110, 115, 151, 157, 159, 167, 351 Paediatric, 110, 351 Palate, 351, 372 Palliative, 351, 376 Palmitic Acid, 178, 351 Pancreas, 231, 281, 293, 301, 310, 331, 333, 351, 368, 370, 379 Pancreatic, 48, 189, 208, 248, 264, 297, 301, 351 Pancreatic cancer, 264, 351 Pancreatic Juice, 301, 351 Pancreatitis, 89, 165, 248, 351 Paneth Cells, 314, 351 Papain, 181, 351 Papillomavirus, 60, 76, 78, 352 Paralysis, 281, 295, 352 Paranasal Sinuses, 352, 369 Parasite, 218, 352 Parasitic, 46, 218, 227, 302, 336, 352 Parietal, 20, 352, 356 Parietal Lobe, 352 Parotid, 49, 352 Paroxysmal, 265, 352 Particle, 352, 378, 382 Parturition, 220, 352 Pathogen, 330, 352 Pathogenesis, 6, 14, 20, 25, 34, 48, 56, 57, 58, 59, 113, 137, 352 Pathologic, 185, 282, 288, 293, 305, 329, 352, 365 Pathologic Processes, 288, 352 Pathologies, 182, 352 Pathophysiology, 36, 38, 352
Pediatrics, 11, 21, 22, 36, 53, 82, 92, 96, 130, 144, 146, 184, 345, 352 Pelvic, 111, 352, 360 Penicillin, 197, 225, 340, 352, 380 Pepsin, 181, 352, 368 Peptide T, 212, 353 Perception, 73, 186, 353, 367 Perfusion, 9, 14, 154, 234, 329, 353 Perinatal, 11, 36, 353 Periodontal disease, 24, 353 Peripheral blood, 96, 100, 206, 353 Peripheral Nervous System, 312, 346, 353, 370, 373 Peripheral Nervous System Diseases, 346, 353 Peripheral Neuropathy, 115, 159, 245, 353 Peritoneal, 289, 333, 348, 353 Peritoneal Cavity, 289, 333, 348, 353 Peroxidase, 8, 337, 353 Peroxide, 353 Petechiae, 325, 353 Petrolatum, 313, 353 Phagocyte, 350, 353 Phagocytosis, 120, 353 Phallic, 318, 353 Pharmaceutical Preparations, 299, 316, 321, 354, 370 Pharmacokinetic, 354 Pharmacologic, 23, 248, 286, 290, 325, 354, 377 Phenolphthalein, 313, 354 Phenotype, 7, 23, 27, 187, 204, 206, 304, 354 Phenyl, 15, 354 Phenylacetate, 190, 354 Phenylalanine, 15, 44, 88, 167, 176, 184, 193, 203, 228, 239, 241, 354, 379 Phenylbutyrate, 15, 28, 101, 190, 354 Phenylephrine, 7, 354 Phorbol, 8, 112, 354, 360 Phospholipases, 354, 369 Phospholipids, 317, 331, 337, 354, 360 Phosphorus, 184, 296, 354 Phosphorylase, 15, 207, 208, 296, 354 Phosphorylase a, 15, 354 Phosphorylase Phosphatase, 354 Phosphorylated, 100, 231, 302, 341, 354 Phosphorylation, 17, 20, 37, 40, 49, 52, 53, 73, 109, 111, 112, 157, 231, 341, 354, 360 Photocoagulation, 302, 354 Photosensitivity, 355, 383 Physical Therapy, 246, 355
400
Glutamine
Physiologic, 48, 223, 283, 293, 325, 341, 355, 359, 363, 365, 375 Pigment, 292, 300, 339, 355, 366 Pilot study, 142, 157, 158, 355 Pituitary Gland, 195, 198, 318, 355 Placenta, 220, 316, 355, 358 Plants, 176, 178, 193, 194, 200, 201, 217, 227, 235, 240, 241, 289, 290, 295, 297, 300, 301, 322, 323, 326, 335, 343, 347, 355, 357, 362, 367, 377, 378 Plaque, 49, 355 Plasma cells, 287, 344, 355 Plasma protein, 110, 157, 284, 314, 355, 361, 369 Plasma Volume, 294, 355 Plasmapheresis, 246, 355 Plasmid, 217, 355, 381 Plasmin, 212, 355, 356 Plasminogen, 355, 356 Plasminogen Activators, 355, 356 Plasticity, 219, 356 Plastids, 300, 349, 356 Platelet Activation, 356, 369 Platelet Aggregation, 286, 347, 356 Platelet Factor 4, 332, 356 Platelets, 292, 296, 347, 356, 376 Platinum, 35, 203, 301, 337, 350, 356 Platinum Compounds, 350, 356 Pleura, 356 Pleural, 192, 348, 356 Pleural cavity, 348, 356 Podophyllotoxin, 316, 356 Point Mutation, 19, 83, 224, 356 Poisoning, 30, 86, 296, 315, 321, 332, 345, 357 Pollen, 283, 357 Polycystic, 265, 357 Polymerase, 357, 359, 365 Polymorphic, 7, 118, 124, 308, 357 Polymorphism, 17, 62, 119, 122, 357 Polyposis, 282, 303, 357 Polysaccharide, 16, 176, 187, 213, 287, 299, 323, 357, 360 Polyunsaturated fat, 214, 357 Population Growth, 228, 357 Posterior, 286, 290, 299, 301, 311, 333, 351, 357, 367 Postmenopausal, 195, 350, 357 Postnatal, 357, 372 Postoperative, 113, 120, 343, 357 Postsynaptic, 357, 369, 374, 375 Post-synaptic, 357, 375
Post-translational, 18, 19, 45, 357 Post-traumatic, 95, 357 Potassium, 4, 128, 175, 184, 193, 219, 234, 235, 340, 357 Potentiate, 58, 357 Potentiation, 18, 230, 337, 357, 369 Practice Guidelines, 262, 270, 358 Precancerous, 184, 358 Precipitation, 50, 235, 358 Prefrontal Cortex, 81, 99, 358 Premalignant, 358 Prescription Fees, 311, 358 Presynaptic, 18, 41, 346, 358, 374, 375 Prevalence, 53, 358 Prickle, 334, 358 Prion, 10, 61, 80, 299, 358 Probe, 23, 25, 358 Probenecid, 9, 358 Proctocolectomy, 96, 358 Profusion, 178, 358 Progeny, 238, 358 Progesterone, 358, 372 Prognostic factor, 81, 359 Progression, 20, 24, 191, 208, 286, 307, 359 Projection, 48, 308, 332, 347, 349, 358, 359, 364 Promoter, 73, 84, 217, 359 Promotor, 359, 365 Prophase, 349, 359, 374 Proportional, 349, 359 Prostaglandin, 7, 51, 359 Prostaglandins A, 330, 359 Prostaglandins E, 96, 129, 359 Prostate, 26, 87, 264, 360, 368 Protease, 10, 48, 202, 203, 221, 239, 345, 360 Protease Inhibitors, 239, 360 Protein Conformation, 285, 334, 360 Protein Folding, 55, 360 Protein Isoforms, 285, 360 Protein Kinase C, 341, 360 Protein Kinases, 39, 48, 114, 342, 360 Protein Transport, 48, 360 Protein-Serine-Threonine Kinases, 341, 360 Protein-Tyrosine Kinase, 321, 360 Proteoglycan, 176, 356, 360 Proteolytic, 47, 97, 167, 170, 174, 239, 284, 303, 318, 351, 355, 356, 360 Prothrombin, 361, 376 Protocol, 8, 11, 33, 188, 361 Protons, 284, 328, 333, 338, 361, 362
Index 401
Proto-Oncogene Proteins, 351, 361 Proto-Oncogene Proteins c-mos, 351, 361 Protozoa, 46, 218, 335, 341, 361, 379 Protozoal, 361, 379 Proximal, 8, 11, 52, 311, 358, 361 Psychiatric, 186, 340, 361, 370 Psychiatry, 35, 57, 85, 90, 94, 99, 318, 361, 381 Psychic, 336, 361, 368 Psychology, 50, 309, 310, 361 Psychomotor, 361, 362 Public Health, 31, 36, 262, 361 Public Policy, 261, 361 Publishing, 60, 179, 361 Pulmonary, 188, 294, 295, 300, 305, 315, 334, 361, 362, 374, 381 Pulmonary Artery, 294, 361, 381 Pulmonary Edema, 300, 334, 362 Pulse, 342, 362 Purines, 19, 228, 231, 291, 362, 369 Purpura, 325, 362 Pustular, 326, 362 Putrefaction, 362 Putrescine, 182, 362, 371 Pyridoxal, 177, 209, 362, 378 Pyrophosphatases, 22, 362 Pyruvate Carboxylase, 28, 44, 102, 201, 362 Pyruvate Dehydrogenase Complex, 40, 362 Q Quality of Life, 33, 362, 374 Quantitative Structure-Activity Relationship, 131, 362 Quaternary, 360, 362 R Race, 51, 160, 340, 341, 362 Radiation therapy, 111, 281, 317, 319, 328, 332, 362 Radioactive, 308, 325, 328, 330, 332, 342, 347, 348, 362, 363, 375, 380 Radioimmunotherapy, 363 Radioisotope, 315, 363, 378 Radiolabeled, 294, 362, 363 Radiotherapy, 199, 294, 362, 363 Raffinose, 184, 363 Rana pipiens, 188, 363 Randomized, 3, 5, 11, 24, 80, 86, 87, 89, 110, 119, 122, 138, 149, 152, 156, 161, 198, 312, 363 Randomized clinical trial, 86, 138, 363 Reabsorption, 358, 363
Reactive Oxygen Species, 45, 57, 363 Reagent, 224, 300, 363 Receptivity, 214, 363 Receptor Aggregation, 114, 363 Receptors, Serotonin, 363, 369 Recombinant, 29, 85, 86, 120, 131, 189, 190, 192, 198, 227, 236, 241, 364, 381 Recombination, 321, 364 Reconstitution, 100, 364 Rectum, 288, 294, 303, 310, 319, 320, 330, 331, 335, 358, 360, 364 Recurrence, 35, 364 Red blood cells, 316, 326, 351, 364, 367 Red Nucleus, 290, 364 Reductase, 11, 67, 76, 284, 364 Refer, 1, 295, 303, 318, 320, 322, 326, 332, 337, 345, 346, 347, 363, 364 Reference Values, 102, 364 Reflex, 18, 246, 364 Refraction, 344, 364, 371 Regeneration, 211, 232, 318, 364 Regimen, 3, 4, 35, 199, 312, 364 Rehydration, 30, 175, 222, 364 Rehydration Solutions, 175, 222, 364 Remission, 364 Renal tubular, 358, 364 Reperfusion, 9, 24, 162, 235, 344, 364 Reperfusion Injury, 235, 364 Repressor, 10, 349, 365 Research Design, 24, 365 Resected, 181, 365 Resection, 130, 139, 156, 177, 209, 248, 365, 369 Resolving, 51, 365 Resorption, 328, 363, 365 Respiration, 297, 342, 365 Respiratory Physiology, 365, 381 Respiratory Therapy, 21, 365 Response Elements, 43, 59, 365 Restitution, 20, 365 Restoration, 180, 198, 344, 355, 364, 365, 383 Resuscitation, 365 Retching, 185, 365 Retina, 6, 44, 301, 304, 313, 335, 345, 349, 365, 366, 382 Retinal, 6, 68, 83, 106, 145, 349, 365, 366 Retinal Detachment, 83, 106, 366 Retinoblastoma, 47, 184, 264, 366 Retinoids, 366, 382 Retinol, 365, 366 Retinopathy, 284, 354, 366
402
Glutamine
Reversion, 366, 379 Rhamnose, 176, 184, 366 Rheumatoid, 350, 366 Riboflavin, 199, 366 Ribonucleases, 188, 366 Ribonucleic acid, 75, 366 Ribose, 142, 184, 191, 217, 231, 282, 366 Ribosome, 55, 366, 378 Rigidity, 355, 366 Risk factor, 4, 53, 124, 225, 246, 366 Ristocetin, 366, 380 Rod, 291, 292, 301, 335, 366 Rotavirus, 175, 366 Rye, 221, 302, 315, 322, 366 S Salicylate, 200, 367 Saline, 211, 285, 295, 367 Saliva, 367 Salivary, 88, 139, 310, 317, 351, 367, 370, 373 Salivary glands, 310, 317, 367, 370 Saphenous, 305, 367 Saphenous Vein, 305, 367 Saponins, 367, 372 Satellite, 33, 224, 247, 367 Saturated fat, 351, 367 Schizoid, 367, 382 Schizophrenia, 83, 94, 99, 166, 184, 312, 367, 382 Schizotypal Personality Disorder, 367, 382 Sclera, 301, 304, 367 Sclerosis, 34, 219, 265, 289, 367 Screening, 61, 131, 201, 227, 242, 243, 302, 367 Sebaceous, 367, 382 Sebaceous gland, 367, 382 Sebum, 203, 367 Second Messenger Systems, 347, 367 Secondary tumor, 340, 368 Secretin, 51, 368 Secretion, 48, 90, 125, 206, 208, 220, 315, 327, 329, 331, 335, 343, 368, 380 Secretory, 16, 48, 368, 374 Sedentary, 138, 178, 227, 368 Seizures, 28, 38, 229, 287, 352, 368 Selenium, 184, 197, 199, 246, 368 Sella, 311, 355, 368 Semen, 360, 368 Semicircular canal, 331, 368 Seminal fluid, 359, 368 Seminiferous tubule, 368, 371 Semisynthetic, 296, 316, 368
Senile, 29, 350, 368 Sensitization, 16, 18, 206, 368 Sepsis, 102, 142, 147, 153, 199, 214, 231, 291, 368 Septic, 16, 103, 289, 368 Sequence Homology, 353, 368 Sequencing, 29, 63, 230, 369, 375 Serologic, 329, 369 Serotonin, 190, 288, 363, 369, 379 Serous, 314, 356, 369 Serum, 3, 50, 102, 107, 118, 154, 196, 197, 206, 211, 238, 284, 286, 303, 306, 364, 369, 379 Serum Albumin, 238, 369 Sex Determination, 265, 369 Shock, 24, 42, 55, 96, 106, 115, 116, 118, 163, 166, 300, 369, 378 Short Bowel Syndrome, 3, 6, 122, 153, 248, 270, 369 Signal Transduction, 5, 11, 18, 26, 44, 45, 73, 158, 206, 325, 331, 369 Sinusitis, 192, 369 Skeletal, 4, 53, 101, 126, 143, 150, 223, 240, 246, 301, 306, 343, 344, 369, 371, 378 Skeleton, 282, 334, 359, 369, 370 Skull, 306, 370, 375 Sleep Deprivation, 53, 370 Small intestine, 16, 105, 128, 175, 185, 223, 247, 292, 311, 314, 327, 329, 332, 334, 345, 370, 379, 381 Smooth muscle, 284, 286, 290, 296, 304, 327, 343, 370, 371, 373 Snake Venoms, 241, 370 Sneezing, 243, 370 Social Environment, 362, 370 Sodium, 4, 5, 15, 90, 175, 184, 190, 194, 197, 219, 225, 234, 340, 363, 370 Sodium Benzoate, 90, 190, 370 Soft tissue, 294, 370 Solid tumor, 103, 130, 204, 286, 370 Solvent, 17, 281, 292, 316, 323, 349, 370 Soma, 370 Somatic, 118, 184, 282, 298, 327, 336, 339, 342, 353, 358, 370, 380 Somatic cells, 298, 339, 342, 370 Somatostatin, 184, 370 Sorbitol, 184, 284, 339, 370 Soybean Oil, 357, 371 Spasm, 305, 346, 371 Specialist, 271, 310, 371 Species, 45, 46, 178, 193, 212, 218, 227, 229, 234, 241, 285, 291, 299, 302, 304, 311,
Index 403
315, 321, 322, 324, 328, 335, 338, 339, 341, 342, 344, 348, 352, 362, 363, 369, 371, 373, 378, 379, 381, 382, 383 Species Specificity, 229, 371 Specificity, 14, 17, 33, 54, 119, 200, 283, 296, 313, 371 Spectinomycin, 66, 371 Spectrum, 176, 371 Sperm, 283, 301, 357, 368, 371, 379 Spermatozoa, 109, 368, 371 Spermidine, 182, 371 Spermine, 182, 371 SPF, 137, 371 Spike, 14, 371 Spinal cord, 193, 289, 295, 299, 300, 312, 314, 320, 340, 346, 351, 353, 364, 371 Spinous, 315, 334, 372 Spleen, 291, 328, 337, 372 Sporadic, 183, 346, 366, 372 Squamous, 138, 142, 315, 372 Squamous cell carcinoma, 138, 142, 315, 372 Squamous cells, 372 Stabilization, 10, 58, 372 Standard therapy, 35, 372 Steel, 301, 372 Stem cell transplantation, 100, 372 Stem Cells, 8, 238, 372 Sterile, 234, 289, 372 Sterility, 307, 372 Steroid, 119, 195, 197, 292, 306, 325, 367, 372 Stimulant, 296, 327, 372, 380 Stimulus, 311, 312, 316, 332, 333, 364, 372, 376 Stomatitis, 157, 199, 372 Stool, 4, 175, 330, 335, 373 Strand, 14, 357, 373 Streptococci, 60, 80, 192, 373 Streptomycin, 197, 373 Striatum, 38, 59, 373 Stroke, 17, 172, 219, 260, 297, 373 Stroke Volume, 297, 373 Stroma, 333, 373 Subacute, 331, 369, 373 Subclinical, 331, 368, 373 Subcutaneous, 176, 229, 282, 312, 348, 352, 373 Subiculum, 327, 373 Sublingual, 49, 373 Submandibular, 49, 373 Submaxillary, 315, 373
Subspecies, 371, 373 Substance P, 291, 340, 364, 366, 368, 373 Substrate Specificity, 16, 46, 56, 373 Suction, 318, 373 Sulfur, 24, 341, 373, 374 Sulfur Compounds, 24, 374 Sunburn, 371, 374 Superoxide, 69, 108, 131, 191, 374 Superoxide Dismutase, 69, 108, 131, 191, 374 Supportive care, 196, 237, 374 Suppression, 21, 44, 77, 374 Suppressive, 191, 374 Surfactant, 240, 374 Suspensions, 5, 151, 374 Sympathomimetic, 311, 315, 347, 374 Symphysis, 360, 374 Symptomatic, 14, 351, 374 Synapses, 193, 337, 347, 371, 374, 375 Synapsis, 374 Synaptic, 32, 33, 38, 41, 151, 337, 369, 374, 375 Synaptic Transmission, 32, 33, 41, 374 Synaptic Vesicles, 374, 375 Synaptosomes, 169, 375 Synchrony, 50, 375 Synergistic, 5, 177, 209, 234, 240, 375 Systemic, 22, 32, 87, 143, 159, 161, 199, 200, 288, 291, 294, 315, 331, 332, 348, 362, 372, 375 T Tachycardia, 291, 375 Tachypnea, 291, 375 Taurine, 8, 85, 90, 112, 128, 130, 158, 184, 292, 375 Technetium, 50, 375 Telangiectasia, 265, 375 Temporal, 7, 107, 327, 375 Temporal Lobe, 107, 375 Terminator, 302, 375 Testicular, 82, 375 Testis, 316, 375 Testosterone, 364, 375 Tetracycline, 45, 66, 375 Tetrahydrocannabinol, 296, 375 Thalamic, 290, 375, 376 Thalamic Diseases, 290, 376 Thalamus, 94, 295, 310, 336, 358, 376 Thalassemia, 171, 376 Theophylline, 362, 376 Therapeutics, 13, 139, 187, 200, 204, 254, 376
404
Glutamine
Thermal, 310, 325, 347, 376 Thiamine, 184, 234, 376 Third Ventricle, 329, 376 Threonine, 10, 109, 176, 178, 184, 203, 232, 341, 353, 360, 361, 369, 376 Threshold, 38, 316, 329, 376 Thrombin, 16, 212, 318, 356, 360, 361, 376 Thrombomodulin, 360, 376 Thrombophilia, 225, 376 Thrombosis, 225, 292, 332, 360, 373, 376 Thrombus, 305, 330, 344, 356, 376 Thymidine, 376, 377 Thymidylate Synthase, 35, 377 Thyroid, 196, 333, 377, 379 Thyroxine, 284, 354, 377 Tin, 353, 356, 377 Tinnitus, 350, 377 Tissue Culture, 6, 197, 210, 346, 377 Tolerance, 50, 123, 215, 282, 322, 325, 377 Tomography, 338, 377 Tooth Preparation, 282, 377 Topical, 245, 316, 328, 351, 353, 377 Topoisomerase inhibitors, 333, 377 Toxic, iv, 8, 13, 32, 34, 42, 52, 177, 181, 188, 191, 196, 200, 202, 209, 218, 221, 224, 229, 251, 284, 292, 302, 308, 315, 322, 324, 329, 340, 346, 356, 362, 367, 368, 370, 377, 380 Toxicokinetics, 50, 377 Toxicology, 25, 86, 262, 377 Toxins, 181, 193, 287, 296, 323, 331, 342, 363, 370, 377 Trace element, 301, 302, 377 Tracer, 108, 185, 378 Trachea, 295, 377, 378 Traction, 213, 301, 378 Tractus, 51, 378 Transaminase, 37, 155, 194, 241, 378 Transcription Factors, 12, 39, 59, 101, 108, 365, 378 Transduction, 5, 11, 22, 56, 369, 378 Transfection, 45, 293, 378 Transferases, 323, 378 Transgenes, 217, 242, 378 Translation, 25, 47, 68, 378 Translational, 25, 378 Translocating, 291, 378 Translocation, 17, 291, 360, 378 Transmitter, 18, 34, 41, 281, 289, 311, 333, 339, 347, 374, 375, 378 Transplantation, 86, 143, 270, 301, 329, 338, 378
Trees, 285, 378 Trifluoperazine, 57, 378 Trinucleotide Repeats, 83, 378 Tropomyosin, 378, 379 Troponin, 24, 378 Trypan Blue, 211, 379 Trypanosomiasis, 218, 379 Trypsin, 211, 301, 379 Tryptophan, 77, 78, 184, 193, 228, 233, 239, 286, 303, 369, 379 Tsetse Flies, 218, 379 Tuberculosis, 31, 68, 69, 79, 99, 105, 243, 305, 379 Tuberous Sclerosis, 265, 379 Tubulin, 58, 341, 379 Tumor Necrosis Factor, 96, 379 Tumour, 96, 159, 320, 379 Tunicamycin, 64, 379 Type 2 diabetes, 23, 208, 379 Typhimurium, 66, 67, 70, 71, 77, 379 U Ubiquitin, 91, 97, 114, 118, 169, 379 Ulcer, 165, 225, 379 Ulcerative colitis, 96, 331, 379 Unconscious, 308, 329, 379 Unsaturated Fats, 217, 379 Untranslated Regions, 25, 380 Uracil, 231, 380 Uraemia, 351, 380 Uranium, 375, 380 Urea, 15, 22, 232, 248, 349, 380 Urethra, 360, 380 Uricosuric, 358, 380 Urinary, 8, 28, 194, 322, 328, 330, 348, 380, 383 Urine, 89, 183, 293, 306, 311, 315, 326, 330, 334, 348, 366, 380 Urogenital, 322, 324, 380 Uterus, 299, 308, 350, 358, 380 V Vaccine, 226, 282, 361, 380 Vacuoles, 313, 349, 380 Vagal, 51, 380 Vagina, 292, 300, 309, 335, 380 Vagus Nerve, 380 Valine, 73, 107, 155, 176, 182, 184, 198, 203, 232, 281, 380 Vancomycin, 64, 86, 380 Vancomycin Resistance, 64, 86, 380 Vascular, 123, 128, 196, 231, 284, 301, 314, 331, 347, 348, 355, 356, 376, 381 Vasculitis, 351, 381
Index 405
Vasodilator, 295, 311, 327, 344, 381 Vasopressor, 24, 381 Vector, 378, 381 Vein, 333, 347, 352, 367, 381 Venom, 193, 241, 381 Venous, 225, 292, 299, 348, 360, 381 Ventilation, 24, 381 Ventricle, 327, 361, 362, 381 Ventricular, 328, 344, 375, 381 Vertebrae, 371, 381 Vertigo, 350, 381 Vesicular, 38, 58, 326, 360, 381 Vestibule, 302, 331, 368, 381 Veterinary Medicine, 176, 261, 381 Vibrio, 300, 381 Vibrio cholerae, 300, 381 Villi, 221, 328, 381 Villous, 175, 221, 298, 301, 381 Vinblastine, 8, 379, 381 Vinca Alkaloids, 381 Vincristine, 379, 381 Viral, 10, 118, 175, 176, 190, 191, 217, 226, 281, 296, 348, 378, 382 Virion, 9, 382 Virulence, 24, 60, 77, 80, 192, 290, 377, 382 Virus, 66, 71, 73, 110, 156, 170, 202, 218, 226, 239, 291, 296, 299, 314, 324, 355, 378, 382 Virus Replication, 202, 382 Viscera, 182, 340, 370, 382 Visceral, 335, 336, 380, 382 Viscosity, 216, 281, 382 Vitamin A, 179, 217, 331, 366, 382 Vitreous Body, 365, 382 Vitreous Humor, 366, 382
Vitro, 8, 10, 19, 25, 26, 30, 34, 38, 39, 41, 44, 47, 48, 50, 52, 57, 59, 72, 73, 90, 96, 98, 103, 111, 120, 124, 125, 129, 130, 137, 142, 150, 197, 204, 234, 298, 326, 330, 366, 377, 382 Vivo, 8, 9, 12, 16, 18, 25, 26, 34, 37, 39, 44, 45, 48, 49, 51, 52, 57, 59, 65, 69, 72, 74, 86, 98, 103, 105, 110, 119, 125, 131, 150, 159, 181, 189, 190, 204, 211, 218, 223, 226, 298, 326, 330, 350, 382 Vulgaris, 136, 145, 160, 382 W Wakefulness, 53, 382 Wart, 246, 382 Wasps, 193, 382 Weight Gain, 53, 185, 222, 382 White blood cell, 287, 336, 337, 338, 343, 344, 347, 355, 382 Windpipe, 377, 382 Withdrawal, 18, 164, 382 Wound Healing, 95, 129, 133, 146, 198, 318, 332, 383 X Xanthine, 231, 383 Xanthophyll, 184, 383 Xenobiotics, 8, 28, 45, 383 Xenograft, 286, 383 Xeroderma Pigmentosum, 35, 383 X-ray, 13, 19, 212, 298, 304, 319, 320, 339, 347, 362, 363, 383 Y Yeasts, 320, 354, 383 Z Zinc Fingers, 183, 383 Zymogen, 301, 360, 383
406
Glutamine
Index 407
408
Glutamine
