GLYCINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Glycine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00490-9 1. Glycine-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 glycine. 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 GLYCINE.................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Glycine .......................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 57 The National Library of Medicine: PubMed ................................................................................ 66 CHAPTER 2. NUTRITION AND GLYCINE ........................................................................................ 111 Overview.................................................................................................................................... 111 Finding Nutrition Studies on Glycine....................................................................................... 111 Federal Resources on Nutrition ................................................................................................. 113 Additional Web Resources ......................................................................................................... 114 CHAPTER 3. ALTERNATIVE MEDICINE AND GLYCINE ................................................................. 117 Overview.................................................................................................................................... 117 National Center for Complementary and Alternative Medicine................................................ 117 Additional Web Resources ......................................................................................................... 130 General References ..................................................................................................................... 133 CHAPTER 4. DISSERTATIONS ON GLYCINE ................................................................................... 135 Overview.................................................................................................................................... 135 Dissertations on Glycine............................................................................................................ 135 Keeping Current ........................................................................................................................ 136 CHAPTER 5. PATENTS ON GLYCINE .............................................................................................. 137 Overview.................................................................................................................................... 137 Patents on Glycine ..................................................................................................................... 137 Patent Applications on Glycine ................................................................................................. 155 Keeping Current ........................................................................................................................ 177 CHAPTER 6. BOOKS ON GLYCINE .................................................................................................. 179 Overview.................................................................................................................................... 179 Book Summaries: Online Booksellers......................................................................................... 179 CHAPTER 7. PERIODICALS AND NEWS ON GLYCINE .................................................................... 181 Overview.................................................................................................................................... 181 News Services and Press Releases.............................................................................................. 181 Newsletter Articles .................................................................................................................... 182 Academic Periodicals covering Glycine ..................................................................................... 183 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 187 Overview.................................................................................................................................... 187 NIH Guidelines.......................................................................................................................... 187 NIH Databases........................................................................................................................... 189 Other Commercial Databases..................................................................................................... 191 APPENDIX B. PATIENT RESOURCES ............................................................................................... 193 Overview.................................................................................................................................... 193 Patient Guideline Sources.......................................................................................................... 193 Finding Associations.................................................................................................................. 195 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 197 Overview.................................................................................................................................... 197 Preparation................................................................................................................................. 197 Finding a Local Medical Library................................................................................................ 197 Medical Libraries in the U.S. and Canada ................................................................................. 197 ONLINE GLOSSARIES................................................................................................................ 203 Online Dictionary Directories ................................................................................................... 203
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GLYCINE DICTIONARY............................................................................................................. 205 INDEX .............................................................................................................................................. 295
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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 glycine 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 glycine, 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 glycine, 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 glycine. 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 glycine, 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 glycine. 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 GLYCINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on glycine.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and glycine, 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 “glycine” (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: •
Renal Insufficiency and Failure Associated with Immune Globulin Intravenous Therapy: United States, 1985-1998 Source: MMWR. Morbidity and Mortality Weekly Report. 48(24): 518-521. June 25, 1999. Contact: Available from Superintendent of Documents, U.S. Government Printing Office. Washington, DC 20402. (202) 512-1800. Available for free in electronic format on the World Wide Web at www.cdc.gov or from CDC's file transfer protocol server at ftp.cdc.gov. Summary: Immune globulin intravenous (IGIV) is an immunoglobulin G preparation made from pooled human plasma stabilized with glucose, maltose, glycine, sucrose, sorbitol, or albumin and is used as prophylaxis or therapy for various medical disorders. This article from the Morbidity and Mortality Weekly Report of the CDC reports on
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renal insufficiency and failure associated with IGIV therapy in the United States between 1985 and 1998. During this time period, the Food and Drug Administration (FDA) received approximately 120 reports worldwide of renal adverse events (RAEs) (i.e., acute kidney failure or insufficiency) following IGIV administration. This report describes the epidemiology of IGIV associated RAEs in the United States and emphasizes the importance of reviewing indications for IGIV use and implementing precautions during its administration. Among the 88 case patients reported in the United States, the media age was 60.5 years and 48 (55 percent) were male. Of the 54 case patients that were reported with conditions associated with acute renal failure, 35 (65 percent) were aged greater than 65 years, 30 (56 percent) had diabetes mellitus, and 14 (26 percent) had prior renal insufficiency. Indications for IGIV use were reported in 85 (97 percent) case patients and included 39 (46 percent) hematologic, 20 (23 percent) immunologic, 17 (20 percent) neurologic, and 9 (11 percent) infectious diseases. Seventy nine (90 percent) case patients received sucrose containing IGIV products, seven received IGIV with maltose or glucose, and two received IGIV in which the stabilizer was undetermined. Approximately 35 (40 percent) patients had severe symptoms requiring dialysis; no significant differences in baseline serum creatinines or other underlying risk factors were found between patients requiring and not requiring dialysis. The mean recovery time of renal function, with or without dialysis, was 10 days after RAE onset; however, 13 (15 percent) of the 88 patients died despite therapy. These patients had severe underlying conditions (i.e., cardiac insufficiency, pneumonia, or systemic lupus erythematosis), and the extent to which RAEs contributed to their deaths was undetermined. Appended to the article is a lengthy editorial note in which the editor comments on the report and emphasizes the importance of monitoring patients, particularly high risk patients, on IGIV preparations. 1 table. 6 references.
Federally Funded Research on Glycine The U.S. Government supports a variety of research studies relating to glycine. 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 glycine. 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 glycine. The following is typical of the type of information found when searching the CRISP database for glycine:
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Project Title: 2D NMR OF ENERGY RESCUE FROM PARP IN BRAIN SLICE HYPOXIA Principal Investigator & Institution: Litt, Lawrence; Professor; Anesthesia & Perioperative Care; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2004; Project Start 01-JUL-1985; Project End 31-MAY-2008 Summary: (provided by applicant): Multinuclear high resolution NMR spectroscopy is used to study metabolic rescue in superfused P7 cerebrocortical slices after energy failure from overactivation of PARP (poly(ADP-ribose)polymerase). DNA damage activates PARP, which cleaves NAD into nicotinamide and ADP-ribose, and then attaches ADPribose polymers onto nuclear proteins. Poly-ADP-ribosylation is removed by PARG (poly-ADP-ribose glycohydrolase). Excessive activation of PARP, alone or together with PARG, can increase NAD consumption. In Specific Aim #1 a paradigm similar to one developed for cell cultures will be used where excessive PARP/PARG activity from MNNG-induced DNA damage depletes NAD, shuts glycolysis, and is fatal except when rescue is provided by PARP/PARG inhibitors or administration of TCAcycle substrates, such as pyruvate, ketoglutarate, and glutamine. After slice superfusion with one or more carbon-13 labeled substrates establishes steady state labeling, PARP activation with and without rescue will be done, and metabolic pathways will be evaluated from isotopomer compositions found in metabolic products extracted with perchloric acid. A 14.1 Tesla system with a cryoprobe will be used to obtain 2D [1 H13C] HSQC (Heteronuclear Single Quantum Coherence) spectra that detects carbon-13 indirectly (excite carbons, detect )rotons, which have greater sensitivity). Comparisons of pyruvate dehydrogenase and pyruvate carboxylase fluxes from pyruvate into the TCA cycle are also used to assess neuron-glial differences in metabolic injury and recovery. Optimum metabolic rescue regimens will be identified. Apoptosis and necrosis will be assessed with immunohistochemistry, Western blots, and fluorescence microscopy. Depletion and recovery of NAD, NTP, NDP and PCr will be monitored with 1D 31P NMR spectroscopy and conventional assays. In Specific Aim #2 PARP is activated in a hypoxia-reoxygenation paradigm previously found by us to show ATP loss, injury and damage by radicals derived from nitric oxide and oxygen. Specific Aim #3 studies protection from oxidative stress. Metabolic augmentation of glutathione will be optimized, using 2D NMR to resolve isotopomers of free glutamate, glycine, and cysteine from isotopomers of the same amino acids bound in glutathione. Knowledge obtained will test hypotheses of metabolic mechanisms and provide insights for fighting PARP/PARG energy depletion so as to increase the brain's ischemic tolerance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROTEINS
ALCOHOL
ACTIONS--MOLECULAR
TARGETS
ON
BRAIN
Principal Investigator & Institution: Harris, Robert A.; Professor of Pharmacology; Biological Sciences; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 29-SEP-1983; Project End 31-MAY-2004 Summary: Our hypotheses are that ethanol alters the function of ion channels by binding within protein cavities and that some structural features of these cavities will be similar for related and unrelated ion channels. In addition, we propose that some behavioral actions of ethanol require enhancement of glycine or GABAA receptor function. Our overall goals are (l) to determine the specific protein regions of several
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brain receptors/channels that are responsible for ethanol action, and (2) to test the importance of two of these receptors in vivo. The first goal will be accomplished by in vitro testing of chimeric and mutated receptors/channels, and the second will use transgenic mice to express mutated receptors that are insensitive to ethanol in vitro. First, we will define the role of specific amino acids in the TM2-3 region of GABAA and glycine receptors in ethanol modulation of receptor function. These studies will be carried out in Xenopus oocytes. To determine if results from GABAA and glycine receptors generalize to another, related, ligand-gated ion channel, we will characterize the response of recombinant neuronal nicotinic acetylcholine receptors to ethanol. Next, we will extend our recent studies showing ethanol activation of G-protein activated inwardly rectifying potassium (GIRK) channels by elucidating the molecular basis of ethanol action on this channel. This will be done by construction of chimeric receptors between GIRK2 and IRK1 channels, followed by mutation of single amino acids. Structural determinants (i.e., amino acid properties and locations) of ethanol sensitivity will be compared for glycine, GABAA, and GIRK channels. Lastly, we will determine the in vivo significance of the glycine and GABA receptors for specific behavioral actions of ethanol by constructing transgenic mice with mutant receptors that are ethanol-resistant. The long-term, health-related, goal of this research is to identify molecular sites of alcohol action that would be useful targets for pharmacotherapies that would reduce alcohol actions such as reinforcement, craving, and dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AMINO ACID TRANSMITTERS IN THE AUDITORY BRAINSTEM Principal Investigator & Institution: Altschuler, Richard A.; Professor; Otolaryngology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-DEC-1986; Project End 31-MAR-2007 Summary: Results now show a diversity in amino acid transmitters and receptor subunits that provide for the specialized shaping of neuronal responses and that their changes can underlie auditory brain stem plasticity. Our first Specific Aim is based on our finding decreased GABA release and correlated decreased inhibition in the inferior colliculus (IC) 3 weeks following deafness. It uses immunocytochemistry and tract tracing to test the hypotheses that decreased GABA release is a consequence of decreased GABA in terminals, with a specific GABA sub-circuit to the IC effected, rather than a "global" decrease in all inputs. Caspary's group found GABA-A receptor subunit changes that correlated with age-related hearing loss, but couldn't differentiate "pure aging" versus "deafness". Our second specific aim uses quantitative in situ hybridization to test if there will be comparable subunit changes in our more "pure deafness" model, as well as changes in glycine receptor subunits in the DCN where a glycine mediated decrease in inhibition is found. We further hypothesize correlation between changes in transmitter and receptor. We predict GABA but not glycine receptor subunit changes in the CIC and glycine but not GABA receptor subunit changes in fusiform cells. Studies will also uses receptor autoradiography to test a functional correlate, ligand binding. Our final specific aim uses gene micro arrays to screen for differential expression following deafness and test the hypothesis that deafness induces decreased expression of presynaptic neurotransmitter- related genes and compensatory expression of postsynaptic genes. It then uses quantitative in situ hybridization to test the hypothesis that changes will be specific to distinct neuron types. These studies will provide new information on the role of transmitters and receptors in central auditory plasticity. This will, in turn, increase our understanding of the molecular basis of central auditory
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system dysfunction and provide clues for interventions that might help improve the reintroduction of hearing following deafness, currently with cochlear prostheses and in the future after hair cell regeneration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANESTHETICS, GABA AND THE INJURED BRAIN Principal Investigator & Institution: Warner, David S.; Professor; Anesthesiology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Perioperative stroke remains a major risk during surgery. Volatile anesthetics protect against experimental brain ischemia but the mechanism is not defined. We hypothesize that volatile anesthetics potentiate GABAergic neurotransmission and enhance CI- influx. This hyperpolarizes neurons delaying time to ischemic depolarization and Ca2++ influx. This hypothesis is derived from observations that volatile anesthetics potentiate GABAA receptors and bicuculline, a GABAA antagonist, reverses isoflurane protection in vitro. We also hypothesize that volatile anesthetic GABAergic properties are more important to protection than glutamate receptor antagonistic properties. We propose these Specific Aims: 1) Define a dose-response for isoflurane protection during rat forebrain ischemia/Compare with efficacy of muscimol, a GABAA receptor agonist/Compare with time to onset of ischemic depolarization and pre-ischemic cerebral metabolic rate; 2) Determine if isoflurane neuroprotection against severe forebrain ischemia is permanent; 3) Compare the relative neuroprotective effect of selective NMDA/AMPA receptor antagonism to isoflurane, which also possesses GABAergic potentiation; 4) Determine the role of GABAA potentiation in isoflurane protection against severe forebrain ischemia. For Specific Aim #4, we will examine: a) if isoflurane protection against forebrain ischemia or striatal NMDA microinjections is reversed by GABAA antagonists (flurothyl, bicuculline, flumazenil), b) if isoflurane delays time to ischemia induced Ca2++ influx and if this is reversed by GABAA antagonists, c) if correction for this delay, by extending ischemia duration, equivalently reverses neuroprotection, d) effects of GABAA beta subunit-targeted deletion (knockout) or striatal antisense oligonucleotide microinjection on in vivo isoflurane protection, e) the extent to which isoflurane provides protection in organotypic hippocampal slices against NMDA excitotoxicity or oxygen/glucose deprivation and respective effects on CI- uptake, f) the extent to which this is reversed by antagonists of the GABAA, GABAB, and strychnine sensitive glycine receptors, and g) relationships between isoflurane and GABAA antagonists on CI- and Ca ++uptake in NMDA stimulated synaptoneurosomes. We believe that GABAAergic pharmacologic properties of volatile anesthetics known to be critical for anesthesia are the same properties that confer cerebral protection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOCHEMISTRY AND PHYSIOLOGY OF PEPTIDE AMIDATION Principal Investigator & Institution: Eipper, Elizabeth A.; Professor; Neuroscience; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, Ct 060302806 Timing: Fiscal Year 2003; Project Start 01-JUN-1998; Project End 31-MAR-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Glycine
Project Title: BRAIN MATURATIONAL CHGS: CHILDHOOD & ADOLESCENCE QUANTITATIVE MORPHOMETRIC Principal Investigator & Institution: Jernigan, Terry L.; Clinical Research Psychologist; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2002 Summary: The primary goal of the proposed study is to identify the brain mechanisms underlying abnormalities in social communication in children. Brain structure, assessed using Magnetic Resonance Imaging (MRI), brain biochemistry, assessed using Magnetic Resonance Spectroscopy (MRS), and social communication, assessed by discourse. repair and thought disorder measures will be compared in three groups of children: 1) children with autistic disorder, 2) children with specific developmental language disabilities (DLD), and 3) age. IQ, socioeconomic status (SES) and sex matched normal children. Specific Aims 1. Using reliable and valid measures of social communication and formal thought disorder, we predict that the social communication deficits in the autistic children will be directly related to severity of the disorder as judged by scores on the ADI. 2. The social communication deficits of the autistic subjects but not the DLD subjects will be associated with structural and functional CNS abnormalities 3. Based on preliminary, results from our pilot study and findings of abnormal cell densities in autistic brains, we predict that we will detect H-1 MRS increases in Nacetylaspartate (NAA) in the frontal lobes of the autistic children, decreases in the choline and myoinositol peaks of temporal lobe areas and increases in the glycine peak of the cerebellum in the autistic subjects but not in the DLD subjects, or the normal subjects. 4. Volumetric measures and grey/white matter ratios of the limbic system and area measurements of cerebellar structures will be smaller in the high functioning autistic subjects as compared to the DLD subjects and the normal children matched by age, IQ, gender and socioeconomic status (SES). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CELLULAR PHYSIOLOGY OF THE INFERIOR COLLICULUS Principal Investigator & Institution: Peruzzi, Daniel; Neuroscience/Histology; New York Inst of Technology Old Westbury 268 Wheatley Rd Old Westbury, Ny 11568 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: This proposal has two specific aims that will add to the understanding of signal processing at the cellular level in the inferior colliculus (IC). The first aim is to investigate whether there is a correlation between neurotransmitter- and receptorimmunoreactivity and cell type as defined by membrane properties and morphology. The second aim is to characterize the synaptic inputs to look for synaptic plasticity in a certain type of IC neuron, the buildup-pauser neuron. By learning about the characteristics that define cell types and extent of synaptic plasticity in the IC we can better understand how incoming information is modified and passed along to other auditory nuclei. Both of these problems will be addressed using intracellular recording in living slices of a rat IC. For the first aim, neurons will be classified according to known action potential firing patterns in current clamp. Morphology will be revealed by biocytin and tissue will be immunostained for neurotransmitter- or receptor- reactivity. Thus, information about action potential firing patterns, morphology and immunohisochemistry will be collected for the same IC neuron. It is expected that neurotransmitter and receptor reactivity will correlate with action potential firing patterns and morphology. Because it receives so much information, synaptic patterns to
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neurons of the IC are complex. In the second aim fibers of the lateral lemniscus or commisure of the IC will be stimulated with an extracellular electrode to drive synaptic inputs. First I will, using any information gained with immunohistochemistry in the first aim as a guide. Pharmacologically characterize the synaptic inputs to buildup-pauser neurons. GABA and glycine are predicted to be important since buildup-pauser neurons are affected by hyperpolarization. Then I will look for the evidence of synaptic plasticity on buildup-pauser neurons. The prediction that, tetanic stimulation builduppauser neurons will show an increase in synaptic weight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHARACTERIZATION OF GAD67-GFP TRANSGENIC MICE Principal Investigator & Institution: Agmon, Ariel; Associate Professor; Neurobiology and Anatomy; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2004 Summary: (provided by applicant): With a few important exceptions, all the neurons in the mammalian nervous system fall into two major classes: excitatory neurons, using glutamate as a neurotransmitter, and inhibitory neurons, using GABA (and in some regions also glycine) as a neurotransmitter. GABAergic neurons play the critically important roles of counterbalancing excitation and of channeling the flow of sensory and motor information in time and in space; loss of cortical GABAergic neurons or impairment of their function is a major factor underlying epilepsy and degenerative motor diseases. Their critical roles notwithstanding, GABAergic neurons remain poorly understood; in most regions they are interspersed among the more numerous excitatory neurons, and studying them has been seriously hampered to date by the lack of a means to identify them reliably in living tissue. The need addressed by the proposed study is for a novel method to identify and visualize GABAergic neurons in living preparations. We have recently made the first step towards addressing this need, by generating several lines of transgenic mice in which expression of green fluorescent protein is driven in a cell-specific manner in putative GABAergic neurons. These lines are potentially an extremely powerful research tool for studying GABAergic neurons in living preparations; however before they can be used for such studies, the molecular genetics of the transgene needs to be characterized, the fidelity of GFP expression in GABA neurons needs to be validated, and normal GABAergic function should be verified. Once these aims are accomplished, the mice will be made available to the scientific community through the NIH-sponsored Mutant Mouse Regional Resource Centers. The Exploratory/Developmental R21 Grant mechanism of support is appropriate, because the proposed project will demonstrate the validity and feasibility of a new tool, the GAD67-GFP transgenic mouse, which could have a major impact on the field of neuroscience by allowing investigators to address crucially important questions regarding GABAergic neurons, questions which were so far difficult or impossible to address. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CONTROL OF GLUTAMATE RECEPTOR ACTIVATION Principal Investigator & Institution: Traynelis, Stephen F.; Associate Professor; Pharmacology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 10-JUL-1998; Project End 31-MAY-2007 Summary: (provided by applicant): N-methyl-D-aspartate-selective glutamate receptors (NMDA-Rs) mediate a slow component of excitatory synaptic transmission in the CNS
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and are involved in synaptic plasticity, learning, and memory. Activation of NMDA-Rs can contribute to the initiation and maintenance of seizures. In addition, stimulation of NMDA-Rs by extracellular glutamate that accumulates during ischemia can lead to cytotoxic levels of Ca2+ and neuronal death. Given this potential danger of NMDA-R overactivation, it is not surprising that NMDA-R function is tightly regulated by a number of endogenous extracellular ions including protons. Extracellular protons inhibit NMDA-R function completely by binding to a single binding site (Hill slope about 1) with a pKa of 7.0 (125 nM H+) or 7.4 (50 nM H+) for recombinant NRI/NR2A and NRI/NR2B receptors. Despite the potential importance of NMDA-R function, an understanding of the basic mechanisms by which NMDA-R channels open is lacking. No conceptual model exists for NMDA receptor function that explains both single channel and macroscopic receptor properties. The experiments outlined for the next period exploit our recent success obtaining excised outside-out patches that contain only one active NMDA-R channel. This single channel approach will be combined with macroscopic current recording and quantitative modeling to explore the mechanism of NMDA-R activation (spec. aims 1-3). Detailed functional information about NMDA-R gating will be required to maximize interpretation of structural information. Understanding NMDA-R gating is also a pre-requisite to understanding both the proton sensitivity of gating and the function of the therapeutically interesting compounds that regulate proton inhibition (aims 4-5). Five questions will be addressed. I. Is NMDA receptor function controlled by two independent gates? 2. Can single channel kinetics and macroscopic current response time course be reconciled by multi-gate models? 3. Do the glycine and glutamate binding subunits contribute kinetically distinct gates to the NMDA receptor pore? 4. Do protons and phenylethanolamines reduce the probability that an agonist-bound receptor will open? 5. Is the structural basis for H+ sensitivity of NMDA and G1uR6 receptors contained in the transmembrane linker regions? Together, these experiments will help define a unifying theory for NMDA receptor function that accounts for single channel and macroscopic behavior. In addition, evaluation of the hypothesis that protonation of a few key residues inhibits channel opening without changing other features of receptor function will increase our understanding of the structural nature of how glutamate receptors open and close in response to full and partial agonists. These experiments also probe the link between gating of NMDA receptors and inward rectifier K+ channels. Finally, we will determine at the single channel level the mechanisms of action of a non-competitive and therapeutically interesting class of antagonists - phenylethanolamines, such as ifenprodil. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF A BIOMIMETIC LUNG SURFACTANT REPLACEMENT Principal Investigator & Institution: Barron, Annelise E.; Assistant Professor; Chemical Engineering; Northwestern University 633 Clark Street Evanston, Il 602081110 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-JUL-2005 Summary: We propose to develop a novel class of biomaterials called "polypeptoids," or poly-N-substituted glycines, and to apply them to a specific biomedical problem: the need for more effective synthetic, functional mimics of the human lung surfactant proteins SP-B and SP-C. Lung surfactant (LS) is a surface-active material that coats the internal surfaces of healthy mammalian lungs and enables breathing, by reducing the surface tension on the alveolar surfaces. LS is composed of 95 percent surface-active lipids and 5 percent surfactant-specific proteins; both lipid and protein fractions are
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necessary for its functioning. Two of these surfactant-specific proteins, SP- B, and SP-C, are especially surface-active and are critical for the proper biophysical functioning of LS in vitro and in vivo. SP-B and SP-C are both small, helical, amphipathic proteins (79 and 35 amino acids, respectively); essentially, just peptides. Premature infants born before about 30 weeks of gestation are born with immature lungs lacking surfactant, and require the delivery of an exogenous lung surfactant replacement at birth to enable mechanical ventilation. At present, the most efficacious LS replacement formulations are animal- derived, and therefore raise concerns about their level of purity, their consistency of formulation, and their potential for pathogen transmission, as do any medicines sourced directly from animals. While synthetic LS replacements do exist, they do not work as well as animal- derived surfactant replacements, primarily because these formulations lack good functional replacements for SP-B and SP-C proteins. We propose to develop functional mimics of SP-B and SP-C based on poly-N-substituted glycines, which are sequence- specific heteropolymers synthesized in a similar manner to synthetic polypeptides, by a facile, automated solid-phase protocol. Peptoids offer the advantage s of protease- resistance, biomimetic helical secondary structure, low immunogenicity, and low cost. Peptoid-based SP-mimics will be synthesized, purified, and their secondary structure and biophysical surface activities will be analyzed in vitro circular dichroism spectroscopy and by equilibrium and dynamic surfactometry. The feasibility of these novel SP- mimics is demonstrated in preliminary work. Promising formulations will be tested in vivo by a collaborator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF FUNCTION IN THE VERTEBRATE RETINA Principal Investigator & Institution: Korenbrot, Juan I.; Professor of Physiology; Physiology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 31-JUL-2006 Summary: (provided by applicant): The goal of this research program is to further our understanding of the developmental maturation of functional networks in the vertebrate retina, and to investigate the signaling cascades that direct and control this maturation. In particular, we propose to test the thesis that neural activity is a signal that helps sculpt intricate, mature circuits in the retina from initially imprecise neuronal connections. To achieve this goal, first, the maturation of the retinal network in the peripheral growth zone of the fish retina will be characterized. In this zone, at the rim of the mature tissue, new retina develops continuously in a process similar, if not identical, to embryological development. Fish offer an experimental model accessible to manipulations not readily possible in the mammalian eye. To characterize circuitry maturation, the electrophysiological properties of ganglion cells, the output neuron of the retina, will be investigated. Developmental changes in both the intrinsic properties of individual ganglion cells and in the retinal network reflected, in turn, in ganglion cell function will be studied. Maturation of neural circuits will be studied through measurements of the spiking activity of developing ganglion cells. The neural networks formed after photoreceptors have matured will be investigated by characterizing the development of the functional properties of light-driven networks. Maturation of the intrinsic electrophysiological properties of developing ganglion cells will be studied through measurements of the biophysical and pharmacological properties of ligandgated membrane currents in single cells. After defining the features of network maturation, we will assess the role of neural activity as a modulator of maturation by
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Glycine
testing the effects on network maturation of blocking specific synaptic activitydependent signaling pathways. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF INHIBITATION IN THE AUDITORY SYSTEM Principal Investigator & Institution: Sanes, Dan H.; Professor; Center for Neural Science; New York University 15 Washington Place New York, Ny 10003 Timing: Fiscal Year 2002; Project Start 01-AUG-1989; Project End 31-MAR-2005 Summary: The long-term objective of this proposal is to identify the cellular mechanisms that regulate inhibitory synapse function during development and following hearing loss. The research plan is divided into three areas: (1) The regulation of inhibitory synapse strength will be studied in the developing gerbil lateral superior olivary nucleus (LSO), using a brain slice preparation. The activity-dependent depression of inhibitory synapses from the medial nucleus of the trapezoid body (MNTB) to the LSO will be examined with whole-cell voltage-clamp recordings. The relationship between depression and inhibitory synapse refinement will be tested with paired recordings from dye-filled MNTB and LSO neurons. The cellular basis for depression will be examined by direct activation or blockade of GABA and glycine receptors, and the use of transgenic receptor deletions in mice. The postsynaptic signalling pathway that induces depression will be tested by intracellular application of kinase and phosphatase antagonists. (2) The affect of deafness on inhibitory synapse function will be examined in the gerbil inferior colliculus. Using a brain slice preparation, gramicidin perforated-patch recordings will be obtained from IC neurons, and the evoked synaptic currents will be monitored in response to lemnisal or commissural stimulation. To determine why inhibitor synapse reversal potential depolarizes in deafened animals, postsynaptic chloride homeostasis will be examined in normal and deafened animals using chloride pump and voltage-gated chloride channel antagonists. The ability of synaptic activity to regulate chloride homeostasis will be assessed by monitoring inhibitory reversal potential before and after a prolonged period of excitatory or inhibitory activity. (3) The in vivo occurrence of inhibitory synaptic plasticity will be examined wit extracellular recordings from juvenile gerbils during sound stimulation. The strength of sound evoked inhibition in the LSO will be assessed before and after coactivation of excitatory and inhibitory pathways, using stimulus patterns that induce inhibitory depression in the LSO brain slice. To determine whether inhibitory synaptic strength declines in LSO following deafferentation, the inhibitory pathway will be stimulated electrically following cochlear ablation. The proposed experiments will demonstrate how inhibitory synapse physiology can be modified in the central auditory system, and suggest how inhibitory dysfunction could affect acoustic processing following profound deafness. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEVELOPMENT OF NEURONAL CIRCUITS IN THE AUDITORY SYSTEM Principal Investigator & Institution: Kandler, Karl; Assistant Professor; Neurobiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-OCT-2006 Summary: (Adapted From The Applicant's Abstract): The long-term objective of this research is to understand the cellular mechanisms by which neuronal activity exerts its effects on the formation, reorganization, and stabilization of precisely organized
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neuronal connections. The aim of the proposed project is to elucidate these mechanisms in the development of tonotopically organized, converging excitatory and inhibitory connections in the auditory brainstem of mammals. Focus will be on the lateral superior olivary nucleus (LSO), a binaural nucleus involved in sound localization, in which tonotopically organized ipsilateral and contralateral glycinergic inputs converge on single cells. Previous studies have shown that glycine and GABA, the inhibitory neurotransmitter in the adult system, are depolarizing in the developing LSO when inhibitory connections are being refined. The applicant will test the hypothesis that the depolarizing action of these inhibitory neurotransmitters represents a novel cellular mechanism for activity-dependent refinement of developing inhibitory synapses. They will use an in vitro brainstem slice preparations from pre- and postnatal rats to determine 1) whether the depolarizing neurotransmitters glycine and GABA increase intracellular calcium concentration in developing LSO neurons, 2) whether depolarizing inhiitory synapses act like excitatory synapses, 3) whether refinement of inhibitory connections in the LSO involves the elimination of functional synapses, and 4) whether depolarizing inhibitory connections in the LSO can express activity-dependent changes in synaptic strength such as LTP and LTD. To achieve these specific aims whole-cell and perforated patch clamp recordings will be combined with single cell tracing, calcium imaging and fast, localized photolytic cleavage of neurotransmitters (photostimulation). The experiments will be important for understanding how neuronal activity participates in the formation and reorganization of auditory circuits involved in sound localization. The proposed research may provide new insights into human communication disorders such as speech perception, specific language impairment and dyslexia that result from impaired auditory processing and that likely have developmental components. Understanding the basic cellular mechanisms that rule the development and plasticity of inhibitory circuits is fundamental for understanding the cause of numerous pathological brain states, including epilepsy, that result from an abnormal organization of inhibitory circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENTAL CONTROL OF THE DIAPHRAGM AND UPPER AIRWAYS Principal Investigator & Institution: Cameron, William E.; Associate Professor; Physiology and Pharmacology; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: (Adapted from the applicant's abstract): This proposal will characterize the postnatal development of the genioglossal and phrenic motoneurons, by correlating physiological changes in membrane conductance and spiking properties with changes in anatomy. The strength of respiratory muscle contraction is determined by the number of respiratory motoneurons activated and their rate of discharge. Both the order in which the neurons are activated and their discharge rates are a function of their resting conductance, that is, the number of membrane channels open at any given time. Most membrane channels are controlled by neurotransmitters and/or by the intrinsic electrical state of the cell membrane. The change in the balance of these two processes are most dramatic during postnatal development. The applicant is interested in these processes that occur in the two respiratory motoneurons that affect the performance of the diaphragm and genioglossus. Activation of these two muscles must be coordinated to move air into the lungs with the least effort; this may be particularly relevant to the pathophysiology of Sudden Infant Death Syndrome (SIDS). In the past period, the
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applicant established that glycine significantly contributed to the increase in resting membrane conductance that occurs at 3 weeks, and that these age-related increases in resting conductance result from an increase in the number of open potassium channels. The proposed studies will be performed on genioglossal and phrenic motoneurons in slice preparations of the rat brainstem and spinal cord. Visually identified motoneurons will be studied from four different age groups (1-2, 5-7, 13-15 and 19-22 days) with a combination of patch-clamp recording, three-dimensional neuronal reconstruction and immunocytochemical localization of certain receptors and ion channels. The application will: 1) examine the anatomy and physiology of glycine, GABA, and glutamate neurotransmitter systems at the four stages during postnatal development; 2) identify specific potassium channels that contribute to the increase in membrane conductance and spike characteristics; and 3) explore the intracellular pathways mediating the enhanced potassium conductance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIABETIC RETINOPATHY: AR1 AS A NOVEL THERAPEUTIC TARGET Principal Investigator & Institution: Smith, Sylvia B.; Professor; Cellular Biology and Anatomy; Medical College of Georgia 1120 15Th St Augusta, Ga 30912 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The goal of this project is to determine the pathogenesis of and neuroprotection against retinal ganglion cell (RGC) death in diabetic retinopathy. Many RGCs die within the first 2 years of disease onset. The RGC death is thought to be due to overstimulation of the N-methyl-D-aspartate (NMDA) receptor that leads to excessive levels of intracellular calcium, which triggers the cell death cascade. Glutamate, which is elevated in the vitreous body and retina of diabetic patients, is the primary excitotoxin that activates the NMDA receptor. Homocysteine, which accumulates in the plasma of diabetic patients, induces RGC death when injected intravitreally. NMDA receptor activation requires co-activation of its glycine binding site and D-serine is the endogenous physiologic ligand for this site. Serine racemase is the enzyme responsible for the endogenous generation of D-serine. One of the goals of the project is to elucidate the molecular events involved in the extracellular accumulation of the MDA receptor agonists, glutamate and homocysteine, and the coagonist D-serine. D-serine and serine racemase are expressed in retina, but their involvement in diabetes has not been investigated. AIM 1 will test the hypothesis that diabetes is associated with increased levels of D-serine and serine racemase leading to enhanced activation of the NMDA receptor by glutamate and homocysteine. AIM 2 will test the hypothesis that diabetes is associated with altered function of transport systems for glutamate (EAATs, x[c-]), homocysteine and D-serine (ATB0,+) and that their altered function may provide the molecular basis for the diabetes-associated increase in extracellular levels of glutamate, homocysteine and D-serine. Therapeutic intervention strategies targeted at blocking NMDA receptor stimulation could prevent RGC death and may delay other manifestations of diabetic retinopathy. Type 1 sigma receptor (sigmaR1) is a nonopiate, nonphencyclidine binding site that demonstrates robust neuroprotective properties including inhibition of ischemia-induced glutamate release and depressed neuronal responsivity to NMDA receptor stimulation. SigmaR1 is expressed abundantly in RGCs and continues to be expressed under hyperglycemic conditions. Agonists specific for sigmaR1 may have potential as therapeutic agents in providing neuroprotection in the early stages of diabetic retinopathy. Our preliminary data show that (+)-pentazocine, a sigmaR1 agonist, prevents RGC death in vitro induced
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by glutamate and homocysteine and in vivo induced by diabetes. AIM 3 will test the hypothesis that sigmaR1 agonists will be protective against RGC death characteristic of diabetic retinopathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIETARY PROTEIN INTAKE AND HUMAN AA METABOLISM Principal Investigator & Institution: Young, Vernon R.; Professor of Nutritional Biochemistry; None; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-SEP-1983; Project End 31-MAR-2006 Summary: This application concerns the dynamic aspects of whole-body acid metabolism in adult humans, with reference to the dietary importance of the nutritionally "dispensable" (non-essential) or "conditionally indispensable" amino acids. Our hypothesis is that, despite a constitutive capacity for de novo synthesis, their cellular availability for tissue/organ protein synthesis and other functions in vivo is determined by the nitrogen and amino acid composition of the diet. We also hypothesize that there is a strict dietary need for a preformed source of alpha-amino nitrogen, additional to that from the indispensable amino acids. A major focus here is on sulfur amino acid (SAA) interrelationships. We hypothesize that dietary cystine is a more efficient source as a glutathione (GSH) precursor than methionine. The SAA aims are: (i) to further explore the interrelationships between methionine and cysteine (or procysteine) intakes on methionine/cyst(e)ine and GSH metabolism in healthy adults, including measurement of isotopic enrichments of plasma homocysteine (hcy)and cystathionine; (ii) to measure rates of GSH synthesis using L-2 5-13C oxothiazolidine-4carboxylic acid (OTZ) as labeled precursor and to use L- 2-13C OTZ as a marker of GSH metabolism; (iii) to study the metabolism of homocysteine, using labeled metaprobes, in relation to SAA intake; (iv) to further refine and improve upon our tracer model of GSH metabolism using measurements of isotopic labeling in glutamyl-cysteine and cysteinyl glycine; (v) to begin to accumulate the data necessary for the eventual construction of a compartmental model of GSH metabolism. With respect to dietary alpha-amino acid nitrogen intake we will (i) use the 24h indicator (13C-leucine) amino acid oxidation technique to evaluate the requirement for a source of alpha-amino N, including an assessment of its role in GSH homeostasis and (ii) use of 15N-homoarginine as a metaprobe for assessing of arginine metabolism. The proposed studies will further establish the quantitative and metabolic role played by the non-specific nitrogen component of the "protein" intake in whole-body protein (nitrogen) and specific amino acid homeostasis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DIMENSIONS AND POLARITY OF ANESTHETIC BINDING SITES Principal Investigator & Institution: Trudell, James R.; Anesthesia; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 15-JAN-2002; Project End 31-DEC-2004 Summary: (provided by applicant): Our long-term goal is to improve the design and administration of volatile anesthetics by learning the molecular mechanisms of anesthesia. Our short-term goal is to understand how volatile anesthetic potency is altered by site-directed mutations in the transmembrane domains of ligand-gated ion channels. Our hypothesis is that cavities within transmembrane domains provide a common motif for volatile anesthetic binding sites within the superfamily of GABA,
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glycine, nicotinic acetyicholine, and 5-NT receptors. We suggest that specific amino acid residues define the dimensions and polarity of these binding sites and thereby determine the relative efficacy of volatile anesthetics. This hypothesis will be tested in two Specific Aims: Aim 1. We will test the hypothesis that variations in the dimensions of cavities within transmembrane subunits determine the relative potency of anesthetics within the superfamily of GABA, glycine, and nicotinic acetyicholine receptors. Mutation of two critical amino acid residues in transmembrane segments of the glycine alpha 1 receptor (S267 and A288) modulates the potentiation of agonists by volatile anesthetics. The volume of these residues is the best predictor of anesthetic potency. We will build molecular models of the transmembrane domains of these subunits and predict additional residues that may define the dimensions of these putative cavities. Aim 2. We will test the hypothesis that variations in the polarity of cavities within transmembrane subunits determine the relative potency of volatile anesthetics. Although the volume of amino acid side-chains has a dominant effect, the distinct in vivo and in vitro pharmacology of pairs of anesthetic isomers demonstrate that the polarity and shape of binding sites is important. We will use molecular modeling to rationalize existing data and predict new site-directed mutations for study by our collaborators in an iterative series of experiments. In summary, our initial computational models with two transmembrane alpha helices have been of value in rationalizing and predicting the effect of site-directed mutations. Building a more complete 3-dimensional model of an anesthetic binding site will allow us to define those molecular properties that confer distinct pharmacologies on volatile anesthetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYNAMIC ASPECTS OF AMINO ACID METABOLISM Principal Investigator & Institution: Matthews, Dwight E.; Chairman/ Professor; Medicine; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-JAN-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EFFECT OF FOLIC ACID AND VITAMIN B6 ON HOMOCYSTEINE Principal Investigator & Institution: Schirch, Laverne G.; Biochemistry; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-JAN-2005 Summary: Elevated homocysteine (Hcy) in the blood is an established risk factor for cardiovascular disease. Increases in dietary folate and B6 have been shown to lower Hcy levels. There are however, certain groups with other health problems where Hcy remains elevated, these include heart transplant recipients, diabetics, women with preclampsia or retarded fetal growth, end stage renal disease and Parkinson's disease. The aim of this proposal is to elucidate how nutritional insufficiency of folate and B6 affect the pathways of Hcy metabolism in mammalian cells. There are four specific aims: (1) the development of rapid enzyme-based assays for 5,10-methyleneTHF, B6 vitamers and homocysteine; (2) to determine the direction of flux of 1-carbon (1-C) groups in the cytosol and mitochondria of cells in culture, with special emphasis on serine hydroxmethyltransferase (SHMT); (3) to determine the role of mitochondria in the supply of 1-C groups to the cytosol; and (4) to determine the relationship of folate pools and metabolic levels of homocysteine with several different cell lines when either folate
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or B6 are limiting growth factors. Three hypotheses will be tested, which are: (1) that the role of cytosolic SHMT is not to generate 1-C units but to regulate the levels of glycine and 5,10-methyleneTHF in the cytosol; (2) that 1-C groups used by the cytosol are generated by the mitochondria as formate; and (3) Hcy levels are related to the level of 5,10-methyleneTHF in the cytosol. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ENERGETICS OF THE FAILING HEART Principal Investigator & Institution: Ingwall, Joanne S.; Professor of Medicine, Physiology; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JAN-2004 Summary: The hypothesis that the failing heart is energy starved is both long-standing and controversial. There is now convincing evidence from both failed human myocardium and animal models of severe heart failure that the [ATP] is as much as approximately 25 percent lower than in normal myocardium. This decrease is due to a loss of the purine pool. Based on results using NMR spectroscopy and chemical assay, we and others have shown that the tissue contents of phosphocreatine (PCr) and creatine and the capacity of the CK reaction (Vmax) are also lower. These observations increase our understanding of two important aspects of cardiac energetics: the kinetics of ATP synthesis and the thermodynamics of ATP utilization, i.e. the chemical driving force for the ATP-consuming reactions. Our observations that the creatine and purine pools are lower in the failing heart have important implications for understanding the energetics of the failing heart. Because the concentrations of these substrates are lower, the velocities of the reactions they support must be lower. However, the driving force for ATPases of muscle contraction may not be compromised. This new information leads to the following hypothesis: that the loss of creatine in the failing myocardium is an important compensatory mechanism, preserving the driving force for the ATPase reactions. Little is known about the regulation of either creatine transport or de novo purine synthesis in the failing heart. Accordingly, the primary goal of the proposed research plan is to define the mechanisms whereby creatine and purine pools are depleted in the failing heart. A closely related goal is to manipulate the ATP/ADP and PCr/creatine ratios in normal and failing hearts (due to prolonged aortic banding in the rat), and in hearts with low CK Vmax caused by gene deletions of specific CK isozymes, to define the energetic state of the failing heart no longer capable of supporting normal contractile performance and contractile reserve. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTION
ETHANOL
EFFECTS
ON
GLYCINE
RECEPTOR/CHANNEL
Principal Investigator & Institution: Ye, Jiang-Hong; Associate Professor Anesthesiology; Anesthesiology; Univ of Med/Dent Nj Newark Newark, Nj 07107
of
Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: Ethanol (EtOH) is an effective brain depressant and an additive drug. Emerging evidence suggests that glycine receptor/channels (GlyRs) are sensitive to pharmacologically relevant concentrations of EtOH. Since glycine inhibits neuronal activity, potentiation of GlyR function would be expected to enhance neuronal inhibition and perhaps contribute to the neuronal depressant effects of EtOH. Therefore, we propose to examine the effects of EtOH on glycine-induced responses of dopaminergic neurons from the ventral tegmental area (VTA) of the brain, the reward
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center for drug abuse. The overall objective of this study is to investigate the mechanisms by which EtOH alteration of GlyR function contributes to the central nervous system (CNS) consequences of alcohol in vivo. To achieve this objective the following three hypotheses will be tested. HYPOTHESIS I is that EtOH interacts with the GlyR. EtOH regulates the excitability of dopaminergic neurons by altering functions of GlyRs. HYPOTHESIS II is that EtOH interactions with the GlyR are modulated by the protein phosphorylation status of the GlyR, the intracellular activity of PKA, PKC and G-proteins. HYPOTHESIS III is that GlyR structure, intracellular C1-concentration of dopaminergic neurons and, consequently, glycine-induced responses and their response to EtOH change with development. These hypotheses will be tested on VTA neurons freshly isolated from both neonatal and mature rats. Whole-cell patch- clamp technique (especially gramicidin perforated patch technique) will be used to record glycineinduced responses, including membrane current, potential and the alteration of spontaneous firing in the absence and presence of EtOH. Specific activators and inhibitors of protein kinases A and C and of G-proteins will be used to identify the enzyme pathways involved in any effects, of EtOH on GlyRs. These studies will significantly advance our understanding of the effects of EtOH on CNS GlyRs at the molecular and cellular levels. A better knowledge of the actions of EtOH in the brain will improve our understanding of related reinforcement mechanisms, which will, in turn, facilitate the identification of strategies which might be of value in the treatment of alcohol abuse and fetal alcohol syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPRESSION OF IMMUNOGLOBULIN GENES Principal Investigator & Institution: Storb, Ursula B.; Professor; Molecular Genetics & Cell Biol; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-JUL-1996; Project End 31-MAY-2006 Summary: (investigator's abstract): This application is for the renewal of two previous grants to study the regulation of B cell development. Our previous work has shown that the expression of Ig-gamma genes in developing B cells blocks their maturation and that substituting with the CH1 and transmembrane domains of mu Ig does not alleviate the block. It is planned to create and study another mu substitution and to investigate molecular/cellular events induced normally by signaling through a mu containing preB cell receptor. The expression of light chains is also tightly controlled in B cell development. Normally lambda1 light chains are in excess of lambda 2 and 3. In the SJL mouse strain, lambda1 expression is dramatically reduced. Previous findings suggest that a point mutation in the lambda1 constant region changing a glycine to a valine codon may be responsible. It is planned to knock-in a valine codon into a wildtype lambdal locus, If this change causes the defect, its molecular and cellular basis will be investigated by cell signaling experiments with various lambda1 mutant chains and by x-ray crystallographic comparison of the wildtype and SJL lambda light chains. Furthermore, based on unexpected results with a control serine knock-in mouse, the mechanism of hyper-activation of the lambda 1 locus by insertion of PGK-neo will be investigated. Understanding the development of B cells and its relationship to Ig gene rearrangement and Ig expression s of basic importance and clinical relevance. The regulation of Ig gene expression in B cells is one of the best studied systems of differentiation, Its complete unraveling will no doubt also give clues for the control of differentiation in general. On the clinical side, many immunological disorders involve B cells, such as autoimmunities, allergies, immunodeficiencies and, probably,
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susceptibility to cancer. Unraveling B cell development should help in understanding the basis of these diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FIBER-OPTIC NEUROTRANSMITTERS
DEVICES
FOR
UNCAGING
OF
Principal Investigator & Institution: Giszter, Simon F.; Assistant Professor; Neurobiology and Anatomy; Drexel University College of Medicine 245 N 15Th St Philadelphia, Pa 19102 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The goal of the proposal is to begin to develop and test a tool that can provide focal control of deep neural tissues including excitation, inhibition and modulation state in a fashion compatible with the range of physiological recording techniques. The tool we are designing and testing is a fiber optic light guide system, which is used for focal uncaging of caged neurotransmitters. This system will be coupled with neural recording and neurotransmitter measurement techniques. Such a combined system will allow rapid excitation, inhibition and/or modulation of target tissues, via post-synaptic mechanisms, while introducing no electrical noise for the recording components. There will also be the potential for feedback regulation of activity and of transmitter levels. To test the tool as it is iteratively prototyped we will use several animal models that are well established and understood in our laboratories. Our project has three Specific Aims: 1. Specific Aim 1 Construction and optimization of an implantable fiber optic uncaging system and recording device for use as an experimental tool, in deep brain stimulation and in other neuroprostheses. Specific Aim 2 Development of caged glycine, serotonin and dopamine for experimental and future clinical applications with the fiberoptic system. Specific Aim 3 Validation of developed devices and caged materials in mammalian CNS using physiological and behavioral assays, first in an acute preparation (cat spinal cord), and then in a chronic preparation (rat parabrachial nucleus). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FOLATE, HOMOCYSTEINE AND METHYL GROUP METABOLISM Principal Investigator & Institution: Wagner, Conrad; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-JUL-2004 Summary: Glycine N-methyltransferase (GNMT), first isolated as a folate binding protein, is an abundant tetrameric enzyme in liver cytosol and the exocrine pancreas. It maintains the ratio of S- adenosylmethionine (SAM) to S-adenosylhomocysteine which regulates all methylation reactions. Folate is needed for the de novo synthesis of methyl groups. A relationship between methyl group metabolism and pancreatic exocrine secretion has been known for many years. We have previously shown that folate deficiency reduces the SAM/SAH ratio and inhibits pancreatic exocrine secretion in vivo. We also showed that treatments which elevated SAH levels in the AR42J pancreatic exocrine cell line inhibited secretion. The C-terminus of small G-proteins is carboxylmethylated in a reversible manner and we also showed that structural analogues of the G-protein C-terminus are potent inhibitors of exocrine secretion. Our first hypothesis is that elevation of SAH levels inhibits methylation of a small G protein necessary for exocrine secretion. Specific Aim 1 is to isolate the putative methylated intermediate(s) involved in exocrine secretion and determine the effects of folate
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Glycine
deficiency on their formation. Recent studies in another laboratory have suggested a novel non-enzymatic role for GNMT subunits as a receptor for certain polycyclic aromatic hydrocarbons in the induction of cytochrome P450. We have shown that fluorescein-labeled GNMT dissociates the tetrameric enzyme into monomers by modifying critical lysines that are used in subunit interaction. The monomeric form rapidly enters the nucleus where it binds to chromatin, probably DNA. Our second hypothesis is that a small amount of monomeric GNMT is formed from the tetrameric enzyme in the cytosol and it is the monomer which can enter the nucleus. Specific Aim 2 is to determine the factors responsible for dissociation of tetrameric GNMT and determine to which region of DNA the dissociated GNMT is bound. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FOLIC ACID REQUIREMENTS AND ONE CARBON METABOLISM Principal Investigator & Institution: Shane, Barry; Professor and Chair; Nutritional Scis & Toxicology; University of California Berkeley Berkeley, Ca 947205940 Timing: Fiscal Year 2002; Project Start 01-JAN-1990; Project End 31-DEC-2004 Summary: Folylpolyglutamates are coenzymes in, and potential regulators of, a large number of reactions known collectively as one carbon (1-C) metabolism. These reactions which include the metabolic cycles for the synthesis of thymidylate, purines and the amino acids, methionine, serine and glycine, are compartmentalized in the mitochondria and cytosol of cells. This application is for the continuation of a series of studies aimed at investigating the control of the 1-C metabolism in cells and animals, and the role that mitochondrial folate metabolism plays in this process. The new application has five specific aims that are designed to test four hypotheses. The specific aims are: (1) to investigate the interrelationship between mitochondrial and cytosolic 1C metabolism; (2) to study the regulation of 1-C entry and loss from the folate pool via the two compartmental forms of serine hydroxymethyltransferase; (3) to study the heterozygous disruption of the mouse methionine synthase gene and other genes for folate-dependent enzymes on the flux of 1-C units through the various metabolic cycles; (4) to investigate the use of the mouse methionine synthase heterozygous knockout as a model for the pathological and metabolic effects of vitamin B12 deficiency; and (5) to examine the regulation of expression of methionine synthase, methylenetetrahydrofolate reductase and serine hydroxymethyltransferase and to clone and characterize additional other genes of folate-dependent 1-C metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GABAC RECEPTORS & MOUSE RETINAL GANGLION CELL RESPONSES Principal Investigator & Institution: Mccall, Maureen A.; Assistant Professor; Psychological and Brain Sciences; University of Louisville Jouett Hall, Belknap Campus Louisville, Ky 40292 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2008 Summary: (provided by applicant): Vision requires the integration of many aspects of the visual field into a cohesive whole that is used by the organism to navigate its environment. The mammalian retina is a laminar structure and each layer is populated by several cell types that combine to define the response properties of the retinal ganglion cells (RGCs), which transmit the signal to the brain. The many aspects of the visual scene are encoded by two parallel pathways within the retina that either detect increases or decreases in light intensity. There are many types of RGCs and their
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responses are defined by the inputs they receive. One key element in shaping their response properties is inhibition, which like other regions of the brain is mediated by glycine and gamma amino butyric acid (GABA). GABA inhibition is mediated by three receptors, GABAA, GABAB and GABAC, all of which are present in the retina. One challenge then is to determine how each of these inhibitory and excitatory inputs shapes the responses of the RGCs. A new tool towards attaining this goal is the ability to manipulate the mouse genome and selectively remove specific inputs, the effect of which then can be assessed on the RGCs. However, unlike the extensive literature for cat, rabbit and primate, relatively little is known about the fundamental properties of murine RGCs. The goal of this proposal is to characterize the response properties of mouse RGCs both in vivo and in vitro, and in particular determine the role that GABACR-mediated input plays in shaping the responses. The specific aims are (1) to determine the effect of eliminating, genetically, GABACR-mediated inhibition on a subset of RGC response properties recorded in vivo, and (2) correlate structure and function of a diverse set of RGCs, and determine the impact of eliminating GABACRmediated input on the response properties of each of these cell types. These data will enhance our understanding of the role of inhibition in shaping the response of the output cells of the retina, and therefore important aspects of integration of information in the visual field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GAMMA SUBUNIT GENES
GCS
REGULATION--REGULATORY/CATALYTIC
Principal Investigator & Institution: Mulcahy, R T.; Professor; Human Oncology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: The non-protein thiol, glutathione (gamma-glutamyl-cysteinyl-glycine, GSH) is a predominant cellular antioxidant and as such serves critical functions in the maintenance of cellular redox balance, provides protection against reactive oxygen species and is involved in the detoxication of xenobiotics either through direct reactions with reactive intermediates or via enzymatic conjugation reactions catalyzed by glutathione S-transferases. Exposure of cells to a number of xenobiotic agents results in a significant increase in the total intracellular GSH content, secondary to transcriptional up-regulation of the genes encoding the two protein subunits (catalytic and regulatory) of gamma-glutamylcysteine synthetase (GCS, EC 6.3.2.2), the rate-limiting enzyme in its de novo synthesis. It is hypothesized that transcriptional up-regulation of the two GCS subunit genes involves similar cis-elements, but distinct combinations of trans- factors, contributing to differential regulation in response to specific inducting agents. Transcription is hypothesized to involve dimeric transcription factors composed of small Maf proteins and various other bZIP family members, including Nrf1, Nrf2, Fos and Jun. Furthermore, transcriptional activation is hypothesized to be mediated by specific MAPK signaling pathways in response to alterations in the cellular redox balance in favor of a more pro-oxidant state. In evaluating these hypotheses, we propose the following Specific Aims: 1. Finalize analysis of cis- elements within the heavy and light subunit promoters to identify those involved in transcriptional activation of the genes in response to beta-NF; tBOOH; menadione, H202 and PDTC. 2. Identify the transactivating factors and their component proteins which are ultimately involved in binding to the specific cis- elements identified in Aim 1. 3. Determine the role that oxidative stress plays in GCS subunit gene induction. 4. Define the signaling pathway(s) involved in up-regulation of GCS subunit genes. The application proposes a
22
Glycine
comprehensive investigation of the nature of the signals, the signaling pathways, and the trans- and cis- factors which in composite constitute the mechanism of GCS gene regulation under constitutive conditions and in response to the selective classes of agents included in the investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METABOLISM
GENETIC
EFFECTS-FOLATE-DEPENDENT
ONE-CARBON
Principal Investigator & Institution: Gregory, Jesse F.; Professor; Food Science & Human Nutrition; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-DEC-2004 Summary: One-carbon (Cl) metabolism consists of the generation of carbon units for use in cellular processes including DNA synthesis, regeneration of methionine (Met) from homocysteine (Hcy), and methylation of many biological compounds. Conditions that impair one-carbon metabolism (e.g. folate deficiency) are associated with elevation in plasma Hcy and increased risk of vascular disease, certain cancers, and neural tube defects. A common mutation of methylene-tetrahydrofolate reductase (MTHFR), known as the "thermolabile" or C677T mutant, has been associated with elevations in plasma IIcy (especially in low folate status), lower plasma folate, altered distribution of erythrocyte folate, potentially increased risk of vascular disease, and decreased risk of colon cancer. The in vivo metabolic effects of the C677T mutation have not been determined directly. Our overall hypothesis is that the rate of acquisition and generation of methyl groups from serine (primary source of C1 units) is reduced in individuals homozygous for the C677T mutation, and that the genotypic effect is greatest when folate nutriture is inadequate. We also hypothesize that the rate of folate-dependent synthesis of nucleotides (purines and thymidylate) will be reduced in folate deficiency but may be enhanced by the C677T mutation. The proposed studies will determine nutritional and genetic dependence of the flow of Cl units from serine (Ser) to Met and from Ser to nucleotides. This protocol also will allow measurement of the transsulfuration pathway of Hcy catabolism important in disposal of excess Hcy. Specific aims. To determine: (a) The kinetics by which Ser serves as a donor of Cl units for methyl group synthesis and nucleotide synthesis and the possible degree of impairment caused by the C677T mutation and/or low folate status. (b) The influence of the C677T mutation and folate status on cellular Cl status as reflected by the distribution of folate species in erythrocytes. (C) The influence of the C677T mutation and folate status on homocysteine catabolism. (d) The relative contributions of cytosolic and mitochondrial metabolism in the generation of Cl units for synthesis of methyl groups and nucleotides. (e) The significance of mitochondrial glycine cleavage in generation of Cl units. Protocol: In the main protocol, healthy adequately nourished human subjects (20-30 yr) will be classified by MTHFR genotype, (homozygous control and homozygous mutant). Subjects will be given infusions with 13C-serine as primary precursor initially and following 8-wk dietary depletion of 120 ugld folate to evaluate the effect of nutritional and genotypic effects on Cl kinetics. Two variations of this study will be conducted to determine the relative roles of mitochondrial and cytosolic routes of Cl generation from serine and the role of the mitochondrial glycine cleavage pathway. In total, these studies will yield new functional data regarding the effects of folate deficiency, and the influence of common polymorphism of MTHFR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLYCINE RECEPTORS AND DISORDERS OF CORTICOGENESIS Principal Investigator & Institution: Kriegstein, Arnold R.; Professor; Neurology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 05-APR-1999; Project End 31-MAR-2004 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: 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 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: HOW KARYOPHERINS MOVE ACROSS THE NUCLEAR PORE COMPLEX Principal Investigator & Institution: Rexach, Michael F.; Biological Sciences; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2007
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Glycine
Summary: (provided by applicant): Karyopherin-mediated protein transport across the nuclear pore complex (NPC) is vital for eukaryotic cells yet the mechanisms of karyopherin translocation across the NPC are unsolved. Tumor suppressor proteins, hormone receptors, and cell-cycle checkpoint control proteins are among the hundreds of essential regulatory proteins that need access across the NPC before executing their function in the nucleus. Thus, it is important to human health issues that we achieve a better understanding of the general mechanisms of nucleocytoplasmic transport. The long-term goal of this project is to understand at a molecular level how karyopherins use their interaction with nucleoporins to move across the NPC while carrying cargo. The experimental strategy is to use chemical crosslinkers to identify Nups that function as "stepping stones" for Kap movement within the NPC, then to characterize in detail the interaction between karyopherins and identified nucleoporins using biochemical techniques, and finally to use the knowledge gained from biochemical analyses to design and conduct experiments that will test in vivo the mechanics of karyopherin movement within the NPC. The yeast S. cerevisiae will be used as a model eukaryote for this research. The specific aims are: i) to test the hypothesis that nucleoporins containing FG repeats function as sequential "stepping stones" in the movement of Kap95p across the NPC, ii) to test the hypothesis that nucleoporins are specifically arranged within the NPC to display a "gradient of affinities" for Kap95p that promotes its movement across the NPC, iii) to identify point mutations in Kap95p that interfere with its ability to dock at distinct Nups and test their effects in vivo, and iv) to conduct a comparative study (as delineated for Kap95p) for two additional karyopherins (the exportin Crm1 p, and the importin Kapi 04p) with the goal of uncovering general and specific features in the paths of karyopherin movement in similar and opposite directions across the NPC. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN MITOCHONDRIAL CI-TETRAHYDROFOLATE SYNTHASE Principal Investigator & Institution: Appling, Dean R.; Professor; Chemistry and Biochemistry; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 25-APR-2002; Project End 31-MAR-2006 Summary: The objective of this proposal is to characterize the mammalian mitochondrial trifunctional enzyme, C1-THF synthase, and determine what role it plays in the metabolism of folate- mediated one-carbon units. Folate metabolism is essential in all cells, and mitochondria play a critical role in these pathways. This is reflected in human diseases associated with mitochondrial defects, such as the mitochondrial myopathies and nonketotic hyperglycinemia, as well as the recently recognized connection between homocysteine and mitochondrial one-carbon metabolism. Elevated plasma homocysteine is now recognized as a major independent risk factor for cardiovascular disease, a leading cause of mortality in the U.S. We have carried out extensive studies on these compartmentalized pathways in yeast, but little is known about the enzymes and their regulation in mammals. Using molecular tools made possible by the Human Genome Project, we are now able to study the mitochondrial pathway in humans and other mammals. The Specific Aims are to: (1) Clone and express a cDNA encoding the human mitochondrial C1-THF synthase; (2) Purify and characterize the human enzyme; (3) Examine the expression and nutritional regulation of mitochondrial C1-THF synthase in human and mouse; and (4) Determine whether mutations in mitochondrial C1-THF synthase are related to neural tube defects or homocysteinemia. The experimental design includes complementation of yeast mutants with the human cDNA and expression in CHO cells to confirm its localization to mitochondria. The protein will be purified for analysis of its kinetics and substrate
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specificity. Tissue distribution in humans will be deduced from measurement of transcript and protein levels in various human tissues. Nutritional regulation studies will be performed in mice, including response to choline or folate deficiency. Metabolic interactions with serine hydroxymethyltransferase and glycine cleavage will be studied by NMR methods. PCR will be used to screen DNAs from patients with NTD or homocysteinemia for polymorphisms in the gene. These studies will add to our knowledge of the normal function of the mitochondrial pathway and should lead to a better understanding of how defects in this pathway contribute to human disease related to homocysteine metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HUMAN MITOCHONDRIAL FOLATE/ANTIFOLATE TRANSPORT Principal Investigator & Institution: Moran, Richard G.; Professor/Director; Massey Cancer Center; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): The inner membrane of the mitochondria has several embedded transport proteins that facilitate the translocation of metabolites and cofactors into the mitochondria. These proteins work in concert with mechanisms in the outer membrane to bring cationic and anionic metabolic intermediates from the cytosol to the matrix of mammalian cells. There are 35 inner mitochondrial wall transporters recognizable in the yeast genome; the function of only 13 are known. We have recently cloned a cDNA that encodes an inner mitochondrial protein that facilitates the transport of folate cofactors into the mitochondria. There are data suggesting that a component of the toxicity of the tetrahydrofolate antimetabolites seen in man may be due to inhibition of this transporter. Mammalian cells deficient in this transporter cannot survive in the absence of glycine. In this application, we propose to study the mechanism of this transporter, defining the substrate specificity for the various forms of the folates found in cells and also for the various antifolates that have been used to treat human cancers. Transport process will be studied in isolated mitochondria and in recombinant protein reconstituted into proteolipid bilayers. The proteins in the outer and inner mitochondrial membrane that bind folates will be defined, as will any binding partners involved in the transport through inner or outer membrane of the mitochondria. The phenotype of mice genetically engineered to lack this transporter will be studied as a model for human genetic deficiencies of mitochondrial folate transport. The binding site for folates in this transporter and the orientation of the transmembrane domains will be determined by site-directed mutagenesis, random mutagenesis of peptides, and epitope mapping. These studies will lead to an understanding of the basic biochemistry of this transport process and will lead to an understanding of the role of the inner membrane folate transporter in antifolate toxicity and in human genetic disorders of folate metabolism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: INTEGRINS
HYPERTENSION
AND
ARTERIAL
INJURY--A
ROLE
FOR
Principal Investigator & Institution: Meininger, Gerald A.; Regents Professor and Associate Head; Medical Physiology; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004
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Glycine
Summary: The overall goal of this project is to test the prevailing hypothesis that hypertension and arteriosclerosis may be linked through a mechanism that involves oxidative stress. Our working hypothesis is that oxidative stress in hypertension and atherosclerosis acts to induce similar alterations in the expression of specific integrins and extracellular matrix (ECM) proteins that are responsible for changes in vasomotor function and vascular smooth muscle (VSM) phenotype. Our recent studies have established a novel link between VSM and endothelial integrins and the control of vascular tone. In addition, preliminary data indicates that oxidative stress can alter the expression of at least one of the VSM integrins linked to vasomotor activity and an ECM protein that is a ligand for this receptor. These altered integrin/matrix interactions may predispose the arterial wall to development of vascular pathology. This project incorporates a model of renal hypertension and atherogenesis that will be studied at various stages of disease development in large, intermediate and microvascular sized arterial vessels. Assessments will be made of the redox status, integrin and ECM profiles and vascular reactivity to soluble and insoluble integrin-binding ligands. These ligands will include synthetic Arginine-Glycine-Aspartic Acid (RGD) containing peptides and type I collagen and osteopontin, which are up-regulated following vascular injury. Our strategy is combining studies of intact vessels, cellular, biochemical and molecular approaches will provide a powerful approach for testing our hypothesis and systematically integrating our results, The specific aims are: Aim 1: Characterize the vasomotor response for large intermediate and small arterial vessels to known integrinbinding peptides, type I collagen and osteopontin at varius stages of development for a rat model of renal hypertension and/or imposed oxidative stress (allylamine treated). Vasoactivity will be correlated with measurements of redox status and integrin/ECM profiles. Aim 2: Characterize the vascular redox status and mechanisms leading to the development of oxidative stress in models of renal hypertension and atherogenesis and evaluate the role of NFkappaB as a common signal transduction pathway. Aim 3. Characterize and evaluate changes in vascular ECM/integrin expression at the gene and protein levels that are associated with renal hypertension or oxidative stress and to define the influence of oxidative stress on extracellular matrix and integrin gene expression. These studies will provide new information that will advance our understanding vascular function in hypertension and atherosclerosis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTERPLEXIFORM CELL FUNCTION Principal Investigator & Institution: Shen, Wen; Physiology and Biophysics; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The interplexiform cell has been the last major class of retinal neurons to be discovered. It provides long distance feedback from the inner retina to the outer retina, yet little is known about the function of this class of neuron. The interplexiform cell is the only neuron that provides glycinergic signals to the distal retina in amphibia. This provides an opportunity to explore its function. In this proposal, I will investigate how glycinergic interplexiform cells regulate the physiology of the distal retina. The overall hypothesis is that glycinergic interplexiform cells enhance the output of photoreceptors and the level of enhancement increases as the retina progresses from a dark to a light adapted state. The first aim will be to determine the mechanisms by which the glycinergic interplexiform cells increase photoreceptor transmitter release. The second aim is to evaluate the direct effect of glycinergic interplexiform cell on horizontal cells, and to discern the mechanism of action. The third
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specific aim is to contrast the physiology of the glycinergic interplexiform cell in the dark and the light adapted retina. The application will place an emphasis on how glycinergic interplexiform cells affect neurotransmitter release in rods and cones, and on the fundamental mechanisms of the glycinergic interplexiform cell in dark and light adapted states in terms of the effects on photoreceptor transmitter release and horizontal cell depolarization. This analysis will serve as a contrast to the dopamine system, another mediator of light adaptation. The results of this study should provide an improved appreciation of the role of the interplexiform cell and should also expand knowledge of the molecular events that occur during light adaptation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ION CHANNELS AND TRANSPORTERS AS GLIOMA-SPECIFIC TARGETS Principal Investigator & Institution: Sontheimer, Harald W.; Professor; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-MAY-2007 Summary: One of the major impediments for the successful treatment of malignant glioma is the unusual ability of glioma cells to disseminate by invasion into healthy brain. Much research effort has focused on understanding the mechanisms underlying cell motility and the cells' interactions with the extracellular matrix environment. Comparatively little, however, is known concerning intrinsic adaptations of glioma cells, which may facilitate cell invasion. Based on our recent findings, we hypothesize that the movement of ions through ion channels and ion transporters aid the growth and dissemination of glioma cells. We suggest that glioma cells show up-regulation of certain C1- and K+ channels not found in normal glia which allow them to rapidly adjust their cell shape and cell volume thereby facilitating cell invasion. Importantly, these channels allow for the secretion of KCI along with water. The resulting cycle of cell shrinkage and subsequent restoration of cell volume enables cells to navigate the tortuous extracellular spaces in brain. In addition, we hypothesize that glioma cells utilizes a cystine-glutamate transporter that releases neurotoxic glutamate to actively kill peritumoral tissue and provide room for tumor growth. In this proposal, we have developed 3 testable hypotheses, which seek to delineate the specific contribution of ion channels and ion transporters to glioma cell invasion and tumor growth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: IRON TRANSPORT AND ERYTHROPOIESIS Principal Investigator & Institution: Andrews, Nancy C.; Associate Professor; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-JUN-1998; Project End 31-MAR-2004 Summary: Disorders of iron metabolism are among the most prevalent cause of human morbidity and mortality worldwide. The recent identification of the gene responsible for hereditary hemochromatosis (HLA-H) represents an important step towards understanding and treating these disorders. The mechanism of action of HLA-H is entirely unknown; it must regulate intestinal iron uptake, but the process is poorly understood. To approach this problem from a novel direction, we took advantage of mice carrying the microcytic anemia mutation (gene symbol mk). These animals are known to have defects in both intestinal and red cell iron uptake. Careful physiology studies performed in a variety of laboratories have indicated that the protein encoded by the mk gene is an important component of the intestinal iron transport apparatus.
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Glycine
We mapped the precise chromosomal location of mk using two large backcross panels totally 1000 informative meioses and identified a single candidate gene, Nramp2, that has features of a ATP- dependent transmembrane heavy metal transporter, and is recombinationally inseparable from the phenotype. We have shown that mk animals derived from two distinct spontaneous mutation events both have a glycine to arginine missense mutations in Nramp2 that disrupts a critical transmembrane domain. Taken in the context of the known defects of the mk mouse, our data strongly support the conclusion that Nramp2 is the intestinal iron transporter. It is ubiquitously expressed, and it also appears to be important for bone marrow iron utilization. The work proposed in this application addresses its mechanism of action in iron transport. The specific aims are (1) to characterize the role of Nramp2 in iron metabolism, by investigating its cellular localization, developing an assay for function, carrying out a structure-function analysis and identifying interacting proteins; (2) to determine the effect of the mk mutation on Nramp stability, localization, and function and (3) to rescue the Nramp 2 defect in mk cells and mice by introducing transgenes encoding Nramp2, or its homolog Nramp1, under the control of selected tissue- specific promoters, and (4) to determine whether human patients with similar phenotypic features have mutations in the Nramp2 gene. We anticipate that the results of this characterization will lead to the development of therapeutic agents to modulate intestinal iron absorption, adding a new treatment modality for iron deficiency and iron overload disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: JUVENILE CONSEQUENCES
ALCOHOL
EXPOSURE:
NEUROBEHAVIORAL
Principal Investigator & Institution: Sircar, Ratna; Psychiatry and Behavioral Scis; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): Alcohol is the number one abused substance among adolescents. Several studies have shown that when adolescents use alcohol, they become excessive users of alcohol, and of other substances of abuse, later in life. Adolescents differ from adults in their response to alcohol in exhibiting less sensitivity to the sedative and motor impairing effects. Adolescent rats exhibit more tolerance to alcoholinduced hypothermia, and greater impairments in spatial memory than adult rats. In adolescent rats, the N-methyI-D-aspartate (NMDA) receptor-mediated synaptic plasticity in the hippocampus is more sensitive to alcohol than adults. Although differences in alcohol sensitivity between adolescent and adult rats have been established, the temporal effect of acute and repeated alcohol exposure during the adolescent period on spatial learning and memory remains unknown. The goal of the proposed study is to investigate the short- and long-term effects of alcohol exposure during the adolescent period on spatial memory. Hypotheses to be tested are: (1) alcohol exposure in adolescent rats cause impairments in spatial memory, (2) behavioral effects of repeated alcohol exposure in adolescent rats are long-term, (3) behavioral effects of alcohol exposure in adolescent rats differ from those in immature and adult rats, and (4) deficits in adolescent alcohol-induced spatial memory are associated with alterations in the NMDA receptor-channel complex. Rats will be exposed to acute and repeated alcohol treatments during the adolescent period and tested for deficits in the reference and visual spatial memory tasks in the Morris Water Maze. Others have already identified specific interactions between alcohol and the major neurotransmitter systems such as glutamate, GABA, dopamine, serotonin, endogenous opioids. In this proposal, adolescent alcohol exposure on the NMDA receptor-channel complex will be
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investigated. The proposed studies will identify neuroadaptive changes of early alcohol exposure and define the plasticity of the central nervous system during the adolescent period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LOSS OF A FOLATE ENZYME: NUTRIENT AND METABOLIC EFFECTS Principal Investigator & Institution: Cook, Robert J.; Research Associate Professor; Biochemistry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-MAR-1996; Project End 31-JUL-2004 Summary: The long-term goal of this project is to investigate the regulation of hepatic folate-dependent one-carbon (1-C) metabolism; specifically to investigate the supply and oxidation of 1-C units from serine, glycine, choline, histidine and formate. A model is proposed for the unidirectional flow of 1-C units generated from serine, glycine and choline in mitochondria via 10-formyltetrahydrofolate (10-HCO-H4PteGlu) and delivered to the cytosol as formate, in adult liver. The key enzyme in the mitochondrial conversion of folate-linked 1-C units to formate is a mitochondrial form of C1tetrahydrofolate synthase (mC1-THFS), and enzyme that has not been purified or characterized from mitochondria. Formate is the predominant source of 1-C units in cytosol and is assimilated into the cytosolic folate pool by conversion to 10-HCOH4PteGlu and conversion to other folate forms by cytosolic (c) C1-THFS. Cytosolic and mitochondrial 10- HCO-H4PteGlu pools are reservoirs of 1-C units that supply the biosynthetic folate-dependent reactions or are oxidized to H4PteGlu and CO2 by isozymes of 10-formyltetrahydrofolate dehydrogenase (FDH). NEUT2 homozygous mice lack both cytosolic and mitochondrial isozymes of FDH and are unable to oxidize 1-C units as 10-HCO-H4PteGlu to CO2 and H4PteGlu. Lack of FDH in homozygous NEUT2 mice results in expanded 10-HCO-H4PteGlu pools and diminished H4PteGlu pools. The changes in the H4PteGlu pools correlates with changes in the protein levels of liver cC1-THFS. It is hypothesized that expression of cC1-THFS is regulated at the transcriptional level by the cytosolic level of H4PteGlu. NEUT2 mice offer a unique opportunity for the study of 1-C metabolism in a system where 1-C units as, 10-HCOH4PteGlu, cannot be oxidized. The specific aims are; 1) purification, characterization and cloning of mC1-THFS; 2) investigation of the promoter region of the cC1-THFS gene and 3), cloning and function of mFDH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MAGNETIC RESONANCE IMAGING OF GLUTATHIONE IN TUMORS Principal Investigator & Institution: Gamcsik, Michael P.; None; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant):Glutathione is a tripeptide normally found in high concentration in normal tissue and frequently elevated in tumor tissue. Glutathione and its oxidized disulfide form the primary reduction/oxidation (redox) buffer in cells. The redox balance in the cell controls gene expression, cell differentiation, proliferation and apoptosis and, therefore, it is not surprising that this balance may be elevated in cancer. In normal tissue glutathione protects the cell from toxicants and the cancer cell has adapted this defense mechanism to shield cells from the effects of anticancer therapies. This results in further elevations in glutathione metabolism in therapy-resistant tumors.
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Glycine
Therefore, the accurate determination of glutathione in extracts from normal and tumor tissue has proven to be invaluable to predicting therapy response in patients. This proposal outlines the development of magnetic resonance imaging (MRI) methods to non-invasively monitor glutathione metabolism in normal and tumor tissue. Several MRI methods will be evaluated including the use of 1H-editing, 2H NMR and 13Cchemical shift imaging. Using the most sensitive method, in vivo images of glutathione content obtained from 9L glioma tumors implanted in the flank of rats will be compared to the concentrations measured biochemically in tissue extracts. All of the imaging modalities will measure static glutathione and require the use of stable isotope incorporation. Isotope incorporation-based methods also allow monitoring of the rate of glutathione metabolism in tissue. These types of dynamic studies may be as important as measuring static glutathione levels to stage tumors and predict therapy response. Due to the unique role played by glutathione in cell proliferation, differentiation and apoptosis, the non-invasive monitoring of glutathione metabolism would offer novel diagnostic and prognostic information on the tumor tissue. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MARIJUANA WITHDRAWAL Principal Investigator & Institution: Walker, J Michael.; Professor and Chairman of Psychology; Psychology; Brown University Box 1929 Providence, Ri 02912 Timing: Fiscal Year 2002; Project Start 01-JUN-1993; Project End 31-MAY-2003 Summary: Recent work has demonstrated that very low doses (1 mug/kg, i.v.) can approximately double the excitatory effect of NMDA iontophoretically applied to hippocampal (CA3) pyramidal neurons. Furthermore, the NMDA antagonist CPP was found to inhibit the increased glucose utilization produced by the sigma ligand DTG (1 mg/kg, i.p.), and CPP blocks the ability of DTG to cause increased dopamine release. Based on these findings it appears that sigma ligands (at least in some cases) positively modulate NMDA responses. Three sets of experiments are proposed to further examine this possibility in order to 1) Further characterize the interactions between sigma and NMDA in the hippocampus; 2) use the radioligand binding techniques to examine whether such interactions can be observed at the level of membrane-receptor interactions; and 3) to determine the generality of these interactions - i.e., to examine whether sigma/NMDA interactions are found in neural systems outside the hippocampus, with special emphasis on the nigrostriatal dopamine system. These experiments are relevant to mental health. Some experiments suggest that sigma ligands may serve as antipsychotic drugs, or as pharmacotherapeutic agents for antipsychotic drug-induced movement disorders. In addition, the investigations in the hippocampus may have relevance to learning and memory and thus have implications for certain mental illnesses such as Alzheimer's disease or other diseases that affect mental health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS MODULATION
OF
INHIBITORY
GLYCINE
RECEPTOR
Principal Investigator & Institution: Thio, Kwee L.; Neurology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: K. Liu Lin Thio, MD, PhD is a pediatric epileptologist who is interested in developing a research career in ion channel modulation because of its importance to understanding and treating neurological diseases such as epilepsy. He has extensive
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experience with cellular neurophysiology but would like to probe the molecular mechanisms underlying ion channel modulation. This requires that he learn the basic techniques of molecular biology, which is one of the goals of this proposal. Several neurological disorders including epilepsy may result, in part, from cortical inhibitory glycine receptor (GlyR) dysfunction. Thus, GlyR modulation is important to understanding and treating neurological disease. Although several modulators of GlyR have been identified, their mechanisms of action are unknown because quantitative pharmacological and electrophysiological studies have not been performed. This study proposes to test three hypotheses regarding the mechanism by which three known GlyR modulators act: 1) GlyR and gamma-aminobutyric acidA (GABAA) receptors interact through the cytoskeleton; 2) Sulfhydryl reducing agents inhibit GlyR by chelating extracellular zinc; 3) Potentiation and inhibition of GlyR currents by barbiturates occur at distinct sites. These hypotheses will be tested by studying the electrophysiological properties of native GlyR in cultured embryonic mouse hippocampal neurons and GlyR expressed at Xenopus oocytes and human embryonic kidney (HEK) 293 cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MECHANISTIC ANALYSIS OF DEFENSIN MICROBICIDAL ACTIVITY Principal Investigator & Institution: Satchell, Donald P.; Pathology; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-JUL-2002 Summary: The central hypothesis of this research is that gene encoded microbicidal peptides released by Paneth cells contribute to innate immunity in the small intestine. The apically oriented secretory granules of Paneth cells contain a-defensins, termed cryptdins, that are potent microbicidal agents in vitro and homologs of agents that mediate intracellular non-oxidative microbial cell killing by phagocytic cells. The objective of this application is to investigate the biological activity and biochemical mechanism of action of these peptides as mediators of bacterial cell death. Antimicrobial peptides mediate innate immunity both in phagocytes and on mucosal surfaces. In the small intestine, Paneth cells release secretory granules rich in bactericidal a-defensin peptides, known as cryptdins. Cryptdins with N-terminally truncated residues and attenuated microbicidal activity have been purified from rinses of adult mouse small intestine. In particular, cryptdin-4 deficient in the N-- terminal glycine ((des-Gly)cryptdin-4) lacks bactericidal activity against Gram-positive bacteria compared to native cryptdin-4. This finding implicate the cryptdin-4 N-terminus as one determinant of microbicidal activity which has lead to the overall experimental goal of this proposal: To investigate the role of specific amino acid side chains in the primary sequence of cryptdin-4 on the bactericidal activity of this peptide as a means of defining its mechanism of action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEMBRANE PROPERTIES OF VERTEBRATE RETINAL NEURONS Principal Investigator & Institution: Lasater, Eric M.; Professor and Vice Chairman; Ophthalmology and Visual Scis; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-AUG-1985; Project End 31-MAR-2004 Summary: (Adapted from applicant's abstract): The goal of the present study is to characterize the functional properties of wide-field retinal amacrine cells as a model system for amacrine cell physiology. The proposed research is designed to study: (1) the
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Glycine
intrinsic membrane properties of these cells after they have been isolated from the retina and maintained in culture; (2) the action of the neurotransmitters glutamate, GABA and glycine for their effect on the amacrine cell response properties; and (3) the interplay between neurotransmitter action and voltage-activated currents. In addition to the above transmitters, the action of the neuromodulator dopamine will also be examined. Following the studies on cultured cells, the retinal slice preparation will be used to investigate the physiological responses of amacrine cells in the context of a functioning retina. Stimuli will be presented and response properties evaluated. A ganglion cell receiving input from the wide-field amacrine cell will be identified, and signal transmission from the amacrine cell to ganglion cell will be studied. Information gathered from the proposed study will be valuable in understanding how signal processing occurs at the level of the last synaptic interface in the retina before information is transferred to the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METABOLIC & DEVELOPMENTAL ASPECTS OF MENTAL RETARDATION Principal Investigator & Institution: Zielke, H. Ronald.; Professor of Pediatrics; Pediatrics; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2004; Project Start 01-MAY-1997; Project End 31-JAN-2009 Summary: (provided by applicant): This renewal application represents a multidisciplinary approach to determine factors that regulate transport, metabolic compartmentation, energy production, synthesis of neurotransmitters and endogenous effectors of neurotransmitter receptors, and cell death. The studies in Project I will focus on mechanisms and role of glutamate formed from glutamine in the interstitial space of the brain. Data suggest that the mechanisms leading to the formation of glutamate in the extracellular space of the brain are different in the normal unstressed brain and in the traumatized brain, such as occur following an episode of hypoxia/ischemia. It is hypothesized that phosphate-dependent glutaminase and gamma-glutamyl transpeptidase are involved. A hypoxia/ischemia rat model and a knock-out mouse models will be used in the study. Project II will address the interrelation among energy metabolism, kynurenic acid synthesis, and glutamatergic mechanisms during development. Kynurenic acid is a broad-spectrum antagonist of the ionotropic excitatory amino acid receptors and preferentially blocks the glycine co-agonist site of NMDA receptors at low concentrations. Therefore, kynurenic acid may influence neuronal vulnerability to excitatory insults by functioning as a modulator of glutamatergic neurotransmission. A knock-out mouse model lacking the enzyme for kynurenine biosynthesis has enhanced sensitivity to excitotoxicity. Studies in Project III address the hypothesis that impairment in energy metabolism, neuronal/glial metabolic trafficking, and neurotransmitter biosynthesis may result in long-term damage to developing brain that result in ongoing cellular damage even after the initial insult has ceased. It will also assess the hypothesis that it is crucial for the brain to maintain the proper balance of production and utilization of lactate, since this monocarboxylic acid is a substrate for developing brain, and possibly for neurons in adult brain. Biochemical and NMR studies will be addressed in animal models of hypoxia/ischemia and hypoglycemia. Studies in Project IV will follow up on the important finding that brain mitochondria from immature rats exhibit resistance to bioenergetic failure caused by exposure to high levels of Ca++ in a hypoxia/ischemia model. These studies may lead to the development of targeted neuroprotective interventions in neonates and children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PEPTIDES
METHOD
FOR
IDENTIFICATION
OF
33
ALPHA-AMIDATED
Principal Investigator & Institution: Consalvo, Angelo P.; Unigene Laboratories, Inc. 110 Little Falls Rd Fairfield, Nj 07004 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Peptide hormones are ubiquitous in nature, and perform cellular functions that are critical to the survival of the organism. Approximately 50 percent of all known peptide hormones are post-translationally modified at the C-terminus by conversion of glycine-extended precursors to the peptideamide. The enzyme that performs this modification is peptidylglycine alpha-amidating mono-oxygenase (PAM). Inhibition of PAM in various cell types in culture can be accomplished by the addition of specific PAM inhibitors, such as 4-phenyl-3-butenoic acid, resulting in the accumulation of glycine-extended hormone precursors in the conditioned medium. The medium will be fractionated by chromatography techniques and the individual fractions assayed by sequential enzyme reactions consisting of PAM -> glyoxylate dehydrogenase or PAM > glyoxal oxidase --> horseradish peroxidase, to yield a color reaction. In Phase I, we will optimize the enzyme reactions using model glycine-extended substrates, and demonstrate feasibility by the isolation of known peptide hormones from CA-77 cells using this technology. During Phase II, the optimized technology will be used to detect novel amidated peptide hormones in neuroendocrine cells, and produce the novel peptides recombinantly to obtain material for a series of physico-chemical and functional characterizations. The success of this project will eventually lead to the development of novel therapeutic peptide drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF TRIGEMINAL INHIBITION Principal Investigator & Institution: Huang, Li-Yen M.; Professor; Marine Biomedical Institute; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): Inhibitory synaptic transmission in nociceptive neurons is largely mediated by glycine receptors (GlyRs). It has been shown recently that intracellular Ca2+ causes a large potentiation GlyR-mediated responses. There is good evidence suggesting that the potentiation is mediated by a diffusible cytoplasmic protein (CytoP). The goal of this project is to develop a new technology to identify the CytoP and study its interactions with GlyRs in trigeminal neurons. We hypothesize that a diffusible CytoP binds to GlyRs at low intracellular concentrations ([Ca2+]i), keeping GlyRs in a low activity state. When [Ca2+]i rises, the protein is rapidly dissociated from GlyRs, resulting in an enhancement of channel activity. To test this hypothesis, we will combine molecular biology, patch-clamp and imaging techniques to determine these interactions in molecular details. The CytoP will be isolated by the two-hybrid method. The interaction of the CytoP with GlyRs will be determine by simultaneously monitor (i) GlyR-mediated currents using the patch clamp technique, (2) intracellular Ca2+ transients using fluorescent Ca2+indicators and (iii) dynamic interactions between GlyRs and cytoplasmic proteins using the frequency resonance energy transfer (FRET) imaging technique. We will then extend this technology to identify CytoP and study the GlyR-CytoP interaction in trigeminal neurons. A better understanding of the mechanism of GlyR modulation will provide important information about the neuronal signaling and may lead to new therapy for orofacial pain.
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Glycine
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ANALYSIS OF ALPHAVIRUS MEMBRANE FUSION PROTEIN Principal Investigator & Institution: Kielian, Margaret C.; Professor; Cell Biology; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2002; Project Start 15-AUG-1995; Project End 31-JUL-2003 Summary: Alphaviruses and flaviviruses are the causative agents of severe human and animal illnesses such as encephalitis, polyarthritis, and dengue fever, with millions of cases in humans occurring per year. These enveloped viruses infect cells via a membrane fusion reaction that merges the virus and cell membranes and releases the viral genome into the cytoplasm. This fusion mechanism involves proteolytic cleavage of a companion subunit to activate the fusion protein, fusion protein trimerization via a non-coiled coil mechanism, and insertion of the internal fusion peptide into the target membrane. Fusion of this class of viruses thus is mechanistically quite different from the well characterize influenza virus fusion reaction, in which the fusion protein itself is cleaved and forms a trimeric coiled-coil structure. The goal of this proposal is to determine which the molecular mechanism of membrane fusion in the alphavirus Semliki Forest virus (SFV), a member of this class of viruses and a highly developed system to study membrane fusion. Three key features of the SFV fusion reaction will be addressed: 1. What are the functions of the E1 internal fusion peptide and transmembrane domain in fusion? Photolabeling will be use to define the region of E1 that inserts into the target membrane during fusion, and mutagenesis will test the role of specific residues in this region. The structure of virus containing a fusion-blocking mutation will be determine by cryo electron microscopy. The role of highly conserved glycine residues within the E1 transmembrane domain will be analyzed. 2. How does the E2 companion subunit interact with E1 and regulate its membrane fusion activity? Virus mutants with alterations in E1/E2 dimer stability will be selected and used to map the protein domains that are important in these subunit contacts. The effects of these mutations on fusion activity will be determined. 3. How does the E1 fusion protein oligomerize to form an E1 homotrimer, a critical step in fusion? This aim will characterize the minimal domain of E1 required to trimerization and the protein conformation changed involved in the E1 monomer to trimer transition. Molecular information on the fusion reaction of viruses in this class will make possible the design of specific inhibitors of key early steps in viral infection, and further our understanding of the ubiquitous membrane fusion reactions important to both viruses and cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROCESSING
MOLECULAR
MECHANISMS
MEDIATING
NF-KB2/P100
Principal Investigator & Institution: Sun, Shao-Cong; Professor; Microbiology and Immunology; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): Signal-induced processing of the nfkb2 gene product, pl00, is a critical mechanism of NF-kB regulation. The full-length pl00 functions as a potent inhibitor of NF-kB, sequestering various NF-kB members in the cytoplasm. Upon processing, the C-terminal half of pl00 is degraded by the proteasome, leading to generation of an active NF-kB component, p52, which is required for peripheral B cell
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growth and function and the formation of germinal centers in lymphoid organs. Emerging evidence suggests that defect in p52 generation causes deficiencies in humeral immune responses, while overproduction of p52 or the loss of intact pl00 is associated with abnormal lymphocyte growth and development of lymphoid malignancies. Since the processing of pl00 serves to both generate p52 and interrupt the inhibitory function of pl00, deregulation of this proteolytic event may have profound effect on lymphocyte growth and function. The overall objective of this application is to understand the molecular mechanism regulating pl00 processing. This knowledge is important for rational development of strategies and therapies to modulate immune responses and treat lymphoid malignancies. We have recently shown that the processing of pl00 is tightly suppressed by its C-terminal sequences and that the active pl00 processing can be induced through its phosphorylation and ubiquitination. Based on these findings, we hypothesize that the signal for constitutive pl00 processing is normally masked by its negative-regulatory sequences and that the inducible processing of pl00 is triggered by its site-specific phosphorylation and ubiquitination. To accomplish the objective of this application, we will pursue four specific aims: (i) define the negative- and positiveregulatory sequences of pl00 processing; (ii) identify and characterize cellular factors regulating the processing of pl00; (iii) investigate how the GRR regulates pl00 processing; (iv) investigate pl00 processing in vivo using transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPROTECTIVE STRATEGIES IN PARKINSONS DISEASE Principal Investigator & Institution: Kanthasamy, Anumantha G.; Associate Professor; Biomedical Sciences; Iowa State University Ames, Ia 500112207 Timing: Fiscal Year 2002; Project Start 01-APR-1999; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) The pathophysiological mechanisms for slow and progressive dopaminergic neuronal cell death in Parkinson's disease (PD) are currently unknown: therefore, only limited therapeutic options are available. Dopamine replacement therapy has been the mainstay of antiparkinson treatment for the past three decades. Nevertheless, no real progress has been made to intervene in the progressive neurodegenerative process underlying Parkinson's disease. Glutamate-mediate excitotoxic mechanisms have been suggested to contribute to the progressive neurodegenerative process by leading to excessive activation of cortical glutamatergic input into the basal ganglia. The concept that NMDA receptor blockage could be beneficial in neurodegenerative disorders is pursued actively, to date, has been limited by toxicity of the glutamate antagonists. The current proposal focuses on developing an innocuous neuro-protective agent by indirectly modulating rather than merely blocking the NMDA receptor. In preliminary studies, we have identified two novel strychnine-insensitive glycine (NMDA)/glycine site antagonists acting on the NMDA receptors that are active in attenuating NMDA-induced dopamine neuronal injuries in vitro. These compounds also show neuroprotection in an animal model of PD. The objectives of the current proposal are: (i) to characterize a series of novel quinoxalinediones, which have preferential selectivity for NMDA/glycine sites, for their neuroprotective properties against NMDA and glutamate-induced dopaminergic neurotoxicity in primary mesencephalic neuronal culture, (ii) to further evaluate their effectiveness in attenuating degeneration of dopaminergic neurons in a mouse model of MPTP-induced PD, (iii) to examine the ability of these novel compounds for mitigating the NMDA receptor mediated oxidative stress, (iv) to determine the long-term tolerability of these compounds, and , (v) to investigate the safety and neuroprotective efficacy of these NMDA/ glycine site antagonists in a non-human primate model
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Glycine
(marmosets) of PD. Together, this systematic approach should lead to significant advances in the development of a rationale-based neuroprotective therapy for the treatment of Parkinson's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NMDA EFFICACY/TRANSDUCTION
RECEPTOR--AGONIST
AFFINITY,
Principal Investigator & Institution: Vandongen, Antonius M.; Associate Professor; Pharmacology and Cancer Biology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: The long term goal of this project is to define the molecular basis of agonist affinity and efficacy in the NMDA receptor, a ligand-gated ion channel that belongs to the glutamate receptor family. Activation of NMDA receptors requires binding of two co-agonists, glycine and L-glutamate, to receptor domains in the in the NR1 and NR2 subunits. Occupancy by both agonists initiates a series of molecular events that culminates in opening of the associated ion channel. The objective of this proposal is to identify specific molecular determinants of the interaction of agonists with the NMDA receptor. The recently published crystal structure of the ligand binding domains of a related glutamate receptor (GluR2) predicts which amino acids are in direct contact with the agonists. Preliminary data from our lab suggest the existence of transduction elements in the glycine binding pocket and a highly conserved region in the M3 transmembrane segment. Therefore, the following specific aims are proposed: (1) To identify amino acid residues that determine agonsist affinity and efficacy. Site-directed mutagenesis has identified many amino acid residues whose mutation caused shifts in the agonist dose-response curves. However, such shifts in agonist sensitivity cannot be interpreted unambiguously. A new approach will therefore be used which can distinguish between mutations that affect agonist affinity or efficacy. By using of cysteine-substitution mutagenesis and thiol-specific modifying reagents, the same population of channels can be studied before and after modification. Full and partial agonists will be employed to unequivocally interpret alterations in efficacy and affinity. Parallel experiments using the GluR2 receptor will be used to confirm the structural assignments. (2) To test the hypothesis that the M3 segment is a transduction segment coupling ligand binding to channel opening. The M3 transmembrane segment of glutamate receptors contains a strictly conserved amino acid sequence. Cysteine substitutions in this region identified a residue for which thiol modification results in constitutively active NMDA receptors. Since this modification requires the presence of agonists, it was hypothesized that M3 undergoes a conformational change upon receptor activation and that thiol modification locks the receptor in the active state. These studies will result in a detailed molecular picture of the dynamic change in structure that accompany activation of the NMDA receptor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NMR STUDIES OF MECHANISMS OF GENERAL ANESTHESIA Principal Investigator & Institution: Xu, Yan; Associate Professor; Anesthesiology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 31-DEC-2003 Summary: The molecular mechanisms of action of general anesthetics remain an enigma. A superfamily of ligand-gated ion channels has been implicated as the primary target sites for general anesthetics. It has become increasingly clear from our own and
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other studies that amphiphilicity in regions near the membrane interface is a unifying property of anesthetic binding site(s). Thus, general anesthetics, but not nonimmobilizers (nonanesthetics), have been shown to target amphiphilic interfacial residues of transmembrane channel peptides, and point mutations in the transmembrane domains II and III (TM2 and TM3) of glycine and gammaaminobutyric acidA (GABAA) receptors can completely abolish or even reverse the sensitivity of these receptors to alcohol and general anesthetics. Complete and detailed elucidation of the structure-function relationship will dramatically advance our understanding of general anesthetic action beyond what was even imaginable in the recent past. This competitive renewal will quantify specific interactions of strategically selected pairs of general anesthetics and nonimmobilizers with the TM2 and TM3 domains of the alpha1 subunit of human glycine receptors (GlyR). State-of-the-art protein expression and purification techniques will be coupled with high-resolution and solid-state nuclear magnetic resonance (NMR) spectroscopy, circular dichroism (CD), and molecular dynamic simulations to accomplish three specific aims: (1) To express the wild-type and mutated TM2 and TM3 segments of GlyR alpha1 subunit for structural study by NMR. (2) To determine, at or near atomic resolution, the structures of the functional TM2 and TM3 segments of the human GlyR alpha1 subunit and the associated anesthetic-insensitive mutants. (3) To investigate the structural motifs contained in TM2 and TM3 for general anesthetic binding, and to quantify the effects of general anesthetic binding on channel dynamics within the determined structural frame, thereby elucidating the structural requirement that controls the channel sensitivity to general anesthetics. The long-term goal is to relate the structural events to functional changes caused by general anesthetics, paving the way for future in vivo and other studies to finally identify the sites of action of general anesthetics in the central nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHENCYCLIDINE ABUSE AND PSYCHOSES: BIOMEDICAL MECHANISMS Principal Investigator & Institution: Javitt, Daniel C.; Director; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, Ny 10962 Timing: Fiscal Year 2002; Project Start 01-JUL-1982; Project End 31-MAY-2006 Summary: (provided by applicant) Phencyclidine (PCP) is a major clinical psychotogenic agent and drug of abuse. PCP and other dissociative anesthetics induce their unique behavioral effects by blocking neurotransmission mediated at the Nmethyl-D-aspartate (NMDA)-type glutamate receptor. In addition to the main agonistbinding site for glutamate, the NMDA receptor complex contains multiple coagonist/modulatory sites, including a strychnine-insensitive glycine-binding site. In rodents, stimulation of the glycine site reverses PCP-induced hyperactivity, whereas in humans glycine and similar agents (e.g., D-serine, D-cyCloserine) ameliorate PCP psychosis-like symptoms of schizophrenia. In CNS glycine levels in the immediate vicinity of NMDA receptors are maintained at low, subsaturating doses by the action of colocalized glycine transporters. Therefore, inhibition of glycine uptake, rather than administration of large doses of glycine, may be a preferred method for elevating glycine levels in the immediate vicinity of NMDA receptors. This is an application for continuation of a project initiated in 1982 to investigate mechanisms underlying PCP induced psychosis. This cycle of the project with investigate effects of subchronic PCP administration in animal models of schizophrenia. Specific measures to be studied include: 1. PCP-induced potentiation of amphetamine-stimulated dopamine release in
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Glycine
prefrontal cortex and striatum; 2. PCP-induced disruption of prepulse inhibition and neurophysiological deficits, similar to those observed in schizophrenia; and 3. PCPinduced behavioral deficits in social interaction models. Projects will also continue ongoing investigations into effectiveness of glycinergic agents, including glycine site agonists (e.g. glycine, D-serine) and glycine transport inhibitors (GTIs) in reversing PCP-induced behavioral, neurochemical and neurophysiological deficits in animals. Effects of glycinergic agents will be compared to those of typical/atypical antipsychotics. The overall goals of the project are 1) to evaluate the potential utility of glycine agonists/GTIs in the treatment of PCP psychosis and PCP psychosis-like symptoms of schizophrenia, and 2) to develop animal models sensitive to the nondopaminergic, as well as dopaminergic, consequences of PCP-induced NMDA receptor blockade. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENERATION
PREBOTZINGER
CIRCUIT
IN
RESPIRATORY
RHYTHM
Principal Investigator & Institution: Mc Crimmon, Donald R.; Associate Professor; Physiology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): There is increasing evidence that an essential component of the rhythm generating circuitry is located within a discrete region of the ventrolateral medulla termed the preBotzinger complex. Nevertheless, an understanding of the preBotzinger contribution to breathing awaits a comprehensive description of the pertinent properties and network interactions of the constituent neurons. The goal of this project to provide a reasonably complete description of the respiratory neuron types present in the preBotzinger complex, including their discharge patterns, response to activation of selected afferent inputs, neurotransmitter (GABA, glutamate, glycine) content and pattern of synaptic connections formed with other preBotzinger neurons. Given the small size of the preBotzinger complex (in the adult rat it is approximately 0.6 mm long and about 1.5 mm in diameter, including dendrites), it is within our means to provide this analysis. Three Specific Aims will be undertaken. In Aim l, intracellular or extracellular recording will be used to classify neurons with respect to discharge pattern and their response to stimulation of vagus and superior laryngeal nerve afferents. The recorded neurons will then be injected with dye. Subsequent immunohistochemical analysis at the light and ultrastructural levels will identify the neurotransmitter content (GABA, glycine, glutamate) and their axonal projection patterns. In Aim 2, synaptic interactions between preB6tzinger neurons will be identified with complementary electrophysiological and anatomical approaches. In the electrophysiological approach, either spike triggered averaging or cross-correlation approaches will be used with paired neuronal recordings. In anatomical experiments intra- or juxtacellular labeling will be used to dye-label cells in 2 different functional groups for subsequent light and ultrastructural analysis of their synaptic interactions. In Aim 3, we will develop a detailed computational model of the preB6tzinger respiratory network using the identified neuronal properties and connectivity. The hypothesis to be addressed is that the neuronal types and synaptic interactions within the preB6tzinger complex are sufficient for respiratory rhythm generation in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREMOTOR CONTROL OF UPPER AIRWAY AND REM SLEEP ATONIA Principal Investigator & Institution: Kubin, Leszek K.; Research Associate Professor of Physiolo; Animal Biology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 21-SEP-1992; Project End 31-MAR-2004 Summary: (Applicant's abstract): Obstructive apneas and hypopneas occur during sleep in 3-5 percent of the population as a result of decrements in the activity of upper airway dilator muscles. The rapid eye movement (REM) state of sleep is characterized by postural atonia and the nadir of the activity in upper airway dilators. Two brainstem sites are critical for this depression of motor activity: 1) the medial pontine reticular formation (mPRF), where cholinergic mechanisms trigger the atonia and modulatory mechanisms contribute to its expression and maintenance; and 2) the medial medullary reticular formation controlling upper airway motoneurons and ascending neurons essential for the maintenance of the atonia. We hypothesize that cholinoceptive mPRF neurons are the target of modulatory effects exerted by aminergic and peptidergic inputs known to affect the expression of REM sleep atonia, send descending projections to the mMRF, and receive feedback pathways ascending from the mMRF. We further hypothesize that the projections descending from the mPRF target in the mMRF subpopulations of premotor neurons that control upper airway (hypoglossal - XII) motoneurons, local inhibitory interneurons whose function is to suppress the activity of medullary serotonin (5-HT)- containing neurons, and ascending neurons that terminate in the mPRF. To address this, in Specific Aim 1 we will determine which neurotransmitter receptors mediate effects in the mPRF neurons projecting to the mMRF. We will determine whether mRNA for muscarinic- and nicotinic-cholinergic, aminergic (5-HT1, 5HT2, alpha2), and peptidergic (VIP, CRF) receptors is present in individual mPRF cells which have been retrogradely labeled from the mMRF, dissociated, and subjected to the single-cell reverse transcription-polymerase chain reaction. In complementary whole cell clamping experiments, we will determine the effects of cholinergic, aminergic and peptidergic agonists on acutely dissociated cells of the mPRF having projections to the mMRF. In Specific Aim 2 we will use anterograde tracing and immunohistochemistry to determine whether axons of the cells located in the cholinoceptive region of the mPRF terminate on mMRF neurons containing glycine, GABA, met-enkephalin, or glutamate. In Specific Aim 3 we will combine anterograde and retrograde tracing to determine whether axons of the cells located in the mPRF terminate on mMRF cells that : a) are premotor to XII motoneurons; and b) have axons ascending to the mPRF, therefore providing the feedback needed to maintain the REM sleep atonia. In Specific Aim 4 we will identify the transmitters present in XII premotor neurons contacted by axon terminals descending from the mPRF using fluorescent labeling and confocal microscopy. The proposed studies will identify the neurochemistry of the pontomedullary pathway responsible for the REM sleep atonia of upper airway motoneurons at the molecular, cellular and network level. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PREVENTION OF IFOSFAMIDE INDUCED NEPHROTOXICITY Principal Investigator & Institution: Nissim, Itzhak; Research Professor Pediatrics; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399 Timing: Fiscal Year 2002; Project Start 01-AUG-2001; Project End 31-JUL-2005
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Glycine
Summary: Ifosfamide (IFO), an alkylating oxazaphosphorine, has been found to be very effective for the treatment of relapsed solid tumors and in patients who respond poorly following treatment with other chemotherapeutic agents. However, the efficacy of IFO is severely limited by a high incidence of nephrotoxicity. This proposal entails a comprehensive investigation of the as yet unknown mechanism(s) involved in IFOinduced renal injury and prevention of such injury by administration of glycine (Gly), which we found to be an effective cytoprotective agent both in vitro and in vivo. Our ultimate goal is to develop a clinically applicable protocol involving administration of glycine with IFO to prevent nephrotoxcity in cancer patients treated with this antineoplastic drug. The main hypothesis to be explored is that the induction of renal injury during IFO treatment is mediated via accumulation in the kidney cortex of one or more of the active metabolites of IFO, i.e., 4-hydroxy-IFO (4- OH-IFO) and/or isophosphoramide mustard (IPM), secondary to depletion of [GSH] by chloroacetaldehyde (CAA) and/or acrolein (ACR). These metabolites may react with SH-groups of the plasma membrane or mitochondrial membrane proteins, thereby damaging cellular integrity. An alternative, but not mutually exclusive hypothesis is that the primary mechanism in evoking renal injury during IFO treatment is mediated via inhibition of mitochondrial oxidative metabolism by CAA and/or ACR, resulting in defective energy production, multiple metabolic abnormalities, and thereby, cellular damage. However, concomitant oral supplementation of Gly with IFO will attenuate IFO-induced nephrotoxicity by maintaining the renal proximal tubule integrity without diminishing the antitumor action of IFO. Unique features of the current proposal are: (a) the successful development of a rat model system for investigation of IFO-induced renal toxicity; (b) the use of Nuclear Magnetic Resonance (NMR), Gas Chromatography-Mass Spectrometry (GC-MS), LC-MS-MS, Laser- Scanning Confocal Microscopy and techniques of molecular biology to explore the biochemical/molecular lesions responsible for IFO-induced renal injury; and (c) a prevention of such injury by oral supplementation of Gly. The proposed studies are of clinical as well as scientific significance. The data to be generated will potentially have considerable importance for prevention of renal dysfunction associated with cancer chemotherapy, and thus allow for a greater therapeutic efficacy and enhanced survival of cancer patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONS
PROTEIN
ARGININE
METHYLATION--STRUCTURES
AND
Principal Investigator & Institution: Cheng, Xiaodong; Professor; Biochemistry; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract) Protein arginine methylation is an abundant post-translational modification that is involved in signal transduction and nuclear transport. The overall goal of this project is to understand the function and regulation of protein arginine methylation by determining the structures of protein arginine methyl transferases (PRMTs) alone and in complex with substrate and/or regulatory proteins. There are many indications that PRMTs may play important and diverse biological roles: (1) the high degree of conservation among different organisms, (2) the presence of at least three family members in mammals, (3) the expression of the protein in many different tissues with both nuclear and cytoplasmic forms, (4) numerous substrates that are involved in important cellular processes, and (5) the interaction of PRMT with upstream regulators. Specifically, the Principal Investigator proposes to determine the structures of (1) rat PRMT 3, (2) rat PRMT 3, peptide
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substrate, and AdoHcy (reaction product) complex, (3) multimeric yeast protein arginine methyltransferase, (4) rat PRMT 1 and hnRNP A1 (protein substrate), and (5) rat PRMT 1 and upstream regulator complex. In addition, he will characterize the substrate preference for different PRMTs, and possibly uncover novel biological substrates for PRMTs. The potential catalytic and sequence recognition regions of PRMT will be confirmed by mutational analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEIN NEOFORMANS
MYRISTOYLATION IN S CEREVISIAE AND C
Principal Investigator & Institution: Gordon, Jeffrey I.; Professor and Head; Molecular Biol & Pharmacology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-MAY-1995; Project End 31-MAR-2005 Summary: N-myristoyltransferase (Nmt) covalently links the 14 carbon fatty acid, myristate, to the N-terminal glycine of nascent eukaryotic and viral proteins. This grant has supported our efforts to examine the enzymology and biological significance of protein N-myristoylation in S. cerevisiae and Cryptococcus neoformans. Genetic studies established that NMT is essential for the viability of C. neoformans. We found that purified fungal and human Nmts have divergent peptide substrate specificities and that these differences can be used to develop a class of peptidomimetic inhibitors that are fungicidal. The structural basis for the differences in peptide substrate specificities between orthologous Nmts needs to be defined to guide design of additional classes of more potent, biologically active inhibitors. We have used X-ray crystallography to determine, at 2.9 Angstrom units resolution, the structure of a ternary complex of S. cerevisiae Nmt1p with a nonhydrolyzable myristoylCoA analog and peptidomimetic inhibitor. Our specific aim 1 will be to compare the structures of ternary complexes of S. cerevisiae, C. neoformans and human Nmts with bound peptide substrates and to test structure/activity relationships by site-directed mutagenesis. The factors that allow fungal pathogens to survive during stationary phase are poorly understood and may have an important impact on pathogenesis. Using S. cerevisiae as a model, we found that defects in protein N-myristoylation impair survival during stationary phase and also accelerate aging. Deletion of 48 genes encoding known or putative Nmt1p substrates in a wild type strain disclosed that starvation sensitivity and rapid aging can be recapitulated by removing Sip2p, a N-myristoylprotein associated with a kinase (Snf1p) involved in regulating global cellular responses to glucose starvation. Our specific aim 2 will be to characterize the mechanisms by which N-myristoylproteins regulate resistance to nutrient deprivation and aging. The Sip2p pathway will be dissected genetically in S. cerevisiae. An expression cloning strategy will be used to identify C. neoformans cDNAs that can complement the stationary phase (and other) phenotypes produced by sip2delta in S. cerevisiae. The C. neoformans ortholog of SIP2 will be recovered and a null allele generated. The impact of the gene deletion on C. neoformans' ability to withstand periods of nutrient deprivation will be examined in culture and in vivo. These studies may yield therapeutic targets for limiting the ability of fungal pathogens to survive in host compartments where nutrients are scarce. They should also provide molecular insights about the relationship between resistance to nutrient deprivation and aging that are applicable to other organisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Glycine
Project Title: REGULATION DEHYDROGENASE
OF
MAMMALIAN
DIHYDROLIPOAMIDE
Principal Investigator & Institution: Patel, Mulchand S.; Professor; Biochemistry; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-DEC-2004 Summary: Dihydrolipoamide dehydrogenase (E3) is a shared component of the three alpha-keto acid dehydrogenase complexes (involved in the oxidation of pyruvate, alpha-ketoglutarate and branched-chain alpha-keto acids) and glycine synthase (involved in glycine oxidation). E3-deficient patients develop severe neurologic disabilities. E3 catalyzes the reoxidation of the dihydrolipoyl moiety of the dihydrolipoyl acyltransferase (E2) component of the complexes and the H protein of glycine synthase. E3 binds non- covalently to the peripheral subunit-binding domain in the E2 component from most species. In eukaryotic pyruvate dehydrogenase complex (PDC), E3 binds to an E3-binding protein (E3BP). The long- term goal of this proposal is to continue a deeper understanding of the subunit-subunit interactions of E3 with E3BP in mammalian PDC, transcriptional regulation of the E3 and E3BP genes and characterization of E3 deficiency using a mouse model. Based on our recent findings, the five specific aims of this proposal are: (i) to develop an E3-deficient mouse model, (ii) to investigate the impairment on brain development and oxidative metabolism of various fuels, (iii) to investigate the subunit-subunit interactions between human E3 with E3BP of PDC, (iv) to determine the genomic structure of the human E3BP gene and its transcriptional regulation, and (v) to characterize a novel transcription factor of the murine E3 gene. Using the combined approaches of homologous recombination and chimeric gene transfer technologies we propose to develop a mouse strain with less than 20% of control E3 activity. Structural impairment in the developing brain will be determined using histological and immunocytochemical analyses. Using recombinant human E3s and E3BPs (wild-type and site-specific mutants), the sites of interaction between these two proteins will be characterized. Using molecular biology techniques, the genomic organization and the proximal promoter region of the human E3BP gene will be characterized. To identify a novel transcription factor (upstream direct repeat element binding protein) for the murine Dld gene, we propose to purify this protein. From its partial amino acid sequence a cloning strategy will be developed to isolate a mouse cDNA clone for analysis. This multi-faceted approach is designed to enhance our understanding of the structure- function relationships of E3 and E3BP interactions, transcriptional regulation of the E3 and E3BP genes, and time-dependent pathological changes in developing brain of E3-deficient mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETINAL DEGENERATION: MOLECULAR AND BIOCHEMICAL ASPECTS Principal Investigator & Institution: Al-Ubaidi, Muayyad R.; Associate Professor; Cell Biology; University of Oklahoma Hlth Sciences Ctr Health Sciences Center Oklahoma City, Ok 73126 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2006 Summary: (provided by applicant): The identification of hundreds of mutations in over sixty retinal genes led to the generation of animal models, which were instrumental in establishing the relationship between the mutation and the disease phenotype. Currently, limited information exists to explain how a mutation leads to apoptosis. For apoptosis to take place an intrinsic or extrinsic signal must first be received by the cell
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followed by the activation of apoptotic executioners. Our hypothesis is that common early molecular events (apoptotic signals) precede the morphologic changes of photoreceptors (apoptotic execution). Our goal is to identify proteins that are modulated during these events. To identify apoptotic signals (Aim 1) we propose to use proteomics, differential display PCR (dd-PCR), and microarrays on the rd mouse, deltaI-255/256 transgenic model of isoleucine deletion at position 255 or 256 in opsin, Bouse transgenic mouse that over-expresses normal opsin, and SV40 T antigen transgenic mice. These models are chosen because, although they suffer from dysfunction resulting from the expression of different genes, synchronized apoptosis in all of them is initiated after P10 and completed by P21. As controls, we will use age matched wt mice and G90D (glycine to aspartic acid in opsin) transgenic model of non-degenerative congenital stationary night blindness. To identify early apoptotic signals, two-dimensional gels will be performed on retinas before any apparent morphologic changes (on P8) and the identity of informative protein spots will be revealed by characteristic peptide mass fingerprinting. Dd-PCR and cDNA arrays will be used to identify the transcripts of genes whose modulations are below proteomics levels of detection. We will also use proteomics to determine the identity and role in apoptosis of several potential stress proteins that are induced in retinas of transgenic mice expressing bcl-2 proto-oncogene (Aim 2). Finally, to elucidate the mechanism through which factors isolated in Aim 1 can initiate apoptosis, we will use protein arrays to identify prospective retinal apoptotic executioners in Aim 3. This research will help identify the principle genes controlling cell death regardless of the initial cellular insult. Uncovering these genes will lend itself to understanding the initiation and execution of retinal apoptosis in degenerative disorders and serves to enhance our understanding of normal age-related cell death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETINAL INHIBITORY GLYCINE RECEPTORS Principal Investigator & Institution: Slaughter, Malcolm M.; Professor; Physiology and Biophysics; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The glycine receptor is a key inhibitory receptor in the retinal inner plexiform layer. It is found in ~ 40% of amacrine cells. Almost all retinal neurons express glycine receptors. Although glycine performs a number of roles in retina, there has not been a description of the different glycine receptors that may exist. This is in contrast to the two other main fast transmitters in retina, GABA and glutamate. Receptor subtypes for both of these neurotransmitters have been identified, extensively described, and shown to play key, distinct roles in retinal physiology. It is evident that the complexity of synaptic communication in retina is largely due to the diversity of GABA and glutamate receptor subtypes. The same level of complexity is not evident at the glycinergic synapse. A major limitation is that there is very little information about glycine receptor subtypes and poor tools to investigate it. The governing hypothesis of this proposal is that there are multiple glycine receptors in retina. The research plan will be to address the functional and pharmacological differences between glycine receptors in retina, correlating this with the properties of glycine subunits. It is known that at least three types of glycine receptor alpha subunit are expressed in retina and they have different distributions. This implies that there are functional differences between the subunits, warranting the anatomical segregation. This study's long term goal is to define the properties of glycine receptor subtypes as they relate to the function of the synapse and the physiology of vision. One motivation
44
Glycine
for this study is our finding that there are fast and slow glycine currents in ganglion cells, that these currents have different pharmacological properties, and that they are differentially regulated by second messenger pathways. This suggests that glycine receptor subtypes exist and that their properties are important in specific retinal functions. A first step in understanding glycine receptor diversity is to develop the tools to identify and characterize glycine receptor subtypes. This proposal will use biophysical, pharmacological, and molecular approaches to develop these tools. Two specific aims are to find agonists and antagonists that can distinguish between glycine receptor subtypes. Another is to characterize GABA receptor antagonists which interact with the glycine receptor. These specific aims are a necessary first step in unraveling inhibitory synapses in retina. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF GLYCINE DECARBOXYLASE IN HEPADNAVIRAL INFECTION Principal Investigator & Institution: Li, Jisu; Assistant Professor; Rhode Island Hospital (Providence, Ri) Providence, Ri 029034923 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2004 Summary: Hepatitis B virus is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC). A better understanding of the viral life cycle may provide targets for the intervention of HBV infection, thus reducing the risk of HBV-related HCC. However, the early stages of the viral life cycle and viral-host interactions that contribute to viral infection and pathogenicity are poorly understood. This 421 exploratory proposal focuses on studies on a hepadna virus interacting protein, p120/glycine decarboxylase. We have previous found that p120 is a binding partner of an avian hepatitis B virus envelope protein. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. It is expressed only in the virus infectable tissues and its expression level is directly correlated with the cellular susceptibility to virus infection. Moreover, viral mutants with an ablated p120-binding site showed reduced infectivity despite wild-type replication capacity. These findings suggest that p120 is associated with the early stage of the viral life cycle. Therefore, we plan to further establish its role in the viral life cycle by genetic approaches. Specific Aim #1 will determine if inhibition of p120 expression or function in well-differentiated duck hepatocytes will reduce susceptibility to viral infection. Specific Aim #2 will examine whether reconstitution of p120 in dedifferentiated duck hepatocytes will restore productive viral infection. In addition, we will determine if p120 is defective in Muscovy ducks, a duck species resistant to hepadnavirus. We will also explore the possibility to restore viral infection by p120 derived from a susceptible Pekin ducks. These studies will provide further information on virus-cell interactions and may lead to development of novel anti-viral strategies for prevention of HBV induced liver cancer. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SITES OF ANESTHETIC ACTION IN INHIBITORY RECEPTORS Principal Investigator & Institution: Greenblatt, Eric P.; Anesthesia; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-FEB-1998; Project End 31-JAN-2003 Summary: Volatile anesthetics (Vas) are invaluable aids in surgical anesthesia, yet serious side effects complicate their use. An understanding of the fundamental
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mechanisms underlying VA action will contribute to the development of more specifically targeted, and thereby safer agents. The clinically essential site of VA action is the central nervous system (CNS). The molecular mechanism of action of VAs in the CNS remains controversial. The effects of such agents in the CNS may be explained in part by their ability to potentiate neuronal inhibition mediated by the neurotransmitters gamma-aminobutyric acid (GABA) and glycine at GABAa and glycine receptors, respectively. Ligand-gated chloride channel receptors exhibit differential sensitivities to the VAs; whereas GABAa and glycine receptors are positively modulated, GABAc receptors are negatively modulated. Such differences suggest that there may be a structural basis for interactions with VAs. Halothane and other halogenated alkane VAs appear to have a different site of action in these receptors, when compared to VA ethers, such as isoflurane and enflurane, or alcohol. This is consistent with data supporting multiple sites of VA action. The goal of this research is to elucidate the molecular site(s) of action of halothane and related VAs in GABAa and glycine receptors using the tools of molecular biology and electrophysiology. The hypotheses are that (a) there are specific sites at which halothane and related VAs interact with these receptors, and (b) these interactions are subunit dependent. The specific aims are: 1) to generate, and study the pharmacology of, chimeric receptors by interchanging portions of GABAa, glycine and GABAc subunits, to identify specific domains of the protein involved in sensitivity to these VAs. Two electrode voltage clamp (TEVC) will be used to record currents from Xenopus oocytes expressing chimeras. 2) to generate, and study the pharmacology of, point-mutated GABAa,glycine and GABAC subunits, to demonstrate that sensitivity to such VAs requires interaction with specific amino acid residues of these proteins. Mutants will be expressed in oocytes and studies by TEVC. 3) to replicate point mutants of interest in other GABAa and glycine subunits, and to study the pharmacology of various subunit combinations, defining the role of subunit dependence in the effects of halothane and related VAs at these sites. These studies will provide insights into the molecular interaction of this group of Vas with specific neuronal components, which may facilitate the design of improved general anesthetics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SPORE PEPTIDOGLYCAN SYNTHESIS IN BACILLUS SUBTILIS Principal Investigator & Institution: Popham, David L.; Assistant Professor; Biology; Virginia Polytechnic Inst and St Univ 460 Turner Street, Suite 306 Blacksburg, Va 24060 Timing: Fiscal Year 2002; Project Start 01-JAN-1998; Project End 31-DEC-2003 Summary: The long-term objectives of the proposed studies are: 1) characterization of the enzymatic activities and gene products involved in synthesis of the peptidoglycan cell wall of bacterial endospores and 2) examination of the role of each type of peptidoglycan structural modification in determining endospore resistance properties. The specific aims are: 1) to determine the structure of the endospore peptidoglycan in the first stages of its synthesis and to track the structure to its final form in the dormant spore; 2) to identify the changes in synthesis of this structure produced by loss of penicillin- binding proteins, autolysins, and sporulation-associated gene products; and 3) to purify and characterize in vitro an enzyme involved in peptidoglycan side chain cleavage and muramic-lactam production. Knowledge of principles of endospore resistance properties, dormancy,and longevity may contribute to better decontamination methods and methods for storage and transport of drugs and vaccines. Peptidoglycan synthesis in general is an attractive target for antibiotic action, further studies of this process will contribute to methods for identification of new antibiotics. Peptidoglycan will be purified from sporulating cultures of Bacillus subtilis by chemical and enzymatic
46
Glycine
treatments, digested with muramidase, and analyzed by high-pressure liquid chromatography (HPLC) using methods previously developed for analysis of dormant sport peptidoglycan. Novel muropeptides will be identified using amino acid analysis and mass spectrometry. Appearance and loss of peptide side chain alanine and glycine residues, muramic- lactam production, and changes in peptide cross-linking will be quantified throughout the sporulation process. The analysis will be repeated using strains lacking individual penicillin-binding proteins, autolysins, and sporulationassociated gene products. The cwlD gene product will be purified and assayed in vitro for muramoyl-L-alanine activity and for muramic-lactam synthesis. Immature peptidoglycan samples from mutant strains and purified muropeptides will serve as substrates in these assays. Reaction progress will be monitored using the HPLC method and by adaptation of the method to capillary electrophoresis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STATE DEPENDENT CONTROL OF MOTORNEURON ACTIVITY Principal Investigator & Institution: Chase, Michael H.; Professor; Physiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-1976; Project End 31-JUL-2005 Summary: Abnormal patterns of motor behavior are a key component of a number of sleep disorders. These patterns of behavior are evidenced, for example, during wakefulness by cataplectic attacks, in which the motor inhibition that normally occurs during active (REM) sleep is expressed during the waking state. On the other hand, there is a lack of motor inhibition during active sleep that occurs in disorders such as REM Sleep Behavior Disorder. These and various other sleep disorders that involve disrupted motor control during active sleep and wakefulness are the clinical bases for the proposed studies dealing with the paradoxical phenomenon of "reticular responsereversal," wherein a brainstem system exerts dual functions that are dictated by the ongoing behavioral state of the animal, i.e., motor activation during wakefulness (and quiet (NREM) sleep) and motor inhibition during active (REM) sleep. We hypothesize that hypocretin, a newly discovered peptide that has been implicated in the generation of narcolepsy/cataplexy, may be the neurotransmitter that is utilized by the system of reticular response-reversal. Our discovery that hypocretin- containing cells in the hypothalamus are active not only during wakefulness, but also during active (REM) sleep, together with our other preliminary studies demonstrating that hypocretin acts at various sites to promote motor activity during wakefulness and to enhance motor inhibition during active sleep, suggest that hypocretin may be the neurotransmitter that sustains this systems' actions at the level of motoneurons as well as supporting its circuitry within the brainstem. Our studies will provide fundamental data, which are currently non-existent, of a) the role of hypocretin in the in vivo control of neuronal (motoneuron) activity, which includes the spontaneous and synaptic drives which are fundamental to determining the activity levels of cells; b) the interaction of hypocretin, in vivo, with classical excitatory and inhibitory neurotransmitters; and c) the role of hypocretin, in vivo, in response-reversal in promoting the non-reciprocal excitation of motoneurons during wakefulness and the non-reciprocal inhibition of motoneurons during active sleep. These data will allow us to determine the veracity of our hypothesis that hypocretin plays a critical role in maintaining active sleep and its physiological components in addition to participating in waking functions and waking control mechanisms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHANNEL
STRUCTURE
OF
GABA-A
RECEPTOR
47
ANION-SELECTIVE
Principal Investigator & Institution: Akabas, Myles H.; Associate Professor; Physiology and Biophysics; Yeshiva University 500 W 185Th St New York, Ny 10033 Timing: Fiscal Year 2004; Project Start 05-MAR-1994; Project End 31-MAR-2008 Summary: (provided by applicant): The GABAA receptors are members of the neurotransmitter-gated ion channel gene superfamily that includes nicotinic acetylcholine, serotonin 5-HT3 and glycine receptors. The GABAA receptors mediate fast inhibitory synaptic transmission in the central nervous system. A long term goal of molecular neuroscience has been to understand the structural bases for the functional properties of these receptors and for their modulation by clinically used medicines and by drugs of abuse. Structure-function studies of these receptors took a quantum leap on June 25, 2003 with the publication of a 4Angstrom resolution closed state structure of the homologous 'Torpedo' acetylcholine receptor (AChR) (Miyazawa et al., 2003). At 4A resolution this structure provides a solid foundation for future studies of protein dynamics and agonist-induced conformational changes. At 4Angstrom resolution the peptide backbone path is well defined but the individual amino acid side chain positions are poorly defined. As expected, in the transmembrane (TM) domain each subunit contains four alpha-helical segments (M1, M2, M3, M4) with the M2 segment forming the channel lining and gate. Surprisingly, the helical TM segments extend approximately 10Angstrom above the extracellular membrane surface where they interact with the largely beta-strand, extracellular, agonist-binding domain. A critical interaction between the extracellular and TM domains is via a residue in extracellular Loop 2 and residues in the M2-M3 loop. This proposal will focus on three aspects of GABAA receptor structure: 1) verifying the applicability of the AChR structure to the GABAA receptor, 2) studying the dynamic motion of the channel in the closed state and 3) studying the conformational changes that occur during channel gating from the closed to the open/desensitized states. Aim #1 will test the hypothesis that the AChR structure is a good model for the GABAA receptor by testing predicted proximity relationships between the M2 and M3 and between the M2 and M1 segments within a subunit. Aim #2 will test Unwin and colleagues' gating hypothesis. Aim #3 will probe changes in the M2 segment tertiary and quaternary structure during gating. Aim #4 will probe the tightness of protein packing around the extracellular half of the M2 segment from the 12' to the 27' levels. Aim #5 will probe the mobility and flexibility of the extracellular helical extension of the M2 segment from the 21' to the 27' level. Successful completion of the proposed experiments will either confirm the AChR structure or will provide an experimental basis for refining the structure. In addition, completion of the proposed experiments will provide new insights into the dynamics of the GABAA receptor channel-lining domain in the resting state and as the channel undergoes its agonist-induced conformational changes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDIES OF A NOVEL CCK-B/GASTRIN RECEPTOR SPLICE VARIANT Principal Investigator & Institution: Hellmich, Mark R.; Surgery; University of Texas Medical Br Galveston 301 University Blvd Galveston, Tx 77555 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-MAY-2006 Summary: (Applicant's Abstract): Colorectal cancer is the third leading cause of cancer death in the United States, Colon carcinogenesis is a complex, multi-step process
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Glycine
involving progressive changes in signaling pathways regulating intestinal epithelial cell proliferation, differentiation and programmed death. The peptide hormone, gastrin 1-17 (G-17), and its non-amidated precursor, glycine-extended gastrin (G-GIy), exert potent trophic effects on colon cancer cells. The long-term goal is to understand the role of these peptide hormones in the regulation of epithelial cell biology and colon carcinogenesis. Although the growth-promoting effect of these peptides on colon cancers has been extensively documented, the identity of the receptors and intracellular signaling pathways involved remain controversial. The investigators have identified and isolated the cDNA for a novel splice variant of the human cholecystokininB/gastrin receptor (CCK-BR), a member of the G protein-coupled receptor (GPCR) superfamily. The splice variant (designated CCK-BRi4sv for intron 4 containing splice variant) encodes a receptor protein containing 69 additional amino acid residues in its putative third intracellular loop domain. CCK-BRi4sv is expressed in adenomatous polyps and colorectal cancers, but not in nonmalignant colonic mucosa adjacent to the cancer. Mouse Balb3T3 cells expressing the splice variant exhibited spontaneous, ligandindependent, oscillatory, increases in [Ca2+]i whereas, the same cells expressing wildtype CCK-BR (CCK-BRwt) did not. Similarly, primary cultures of human cells isolated from freshly resected colorectal cancers exhibited, ligand-independent, oscillatory increases in [Ca2+]. For both Balb3T3 and primary tumor cells, application of G-17 (10 and 200 nM, respectively) caused an increase in [Ca2+]i. Selective CCK-BR antagonists blocked the G- 17-stimulated Ca2+ responses, but not the spontaneous [Ca2+]i oscillations. In addition to spontaneous intracellular signaling, BaIb3T3 cells expressing CCK-BRi4sv exhibited an increased rate of cell proliferation (approximately 2.5-fold), in the absence of G-17, compared to cells expressing wild-type CCK-BR (CCK-BRwt). Based on these findings, the PI hypothesizes that CCK-BRi4sv may regulate colorectal cancer cell growth through both a gastrin-independent and -dependent mechanism and thus play a significant role in colorectal carcinogenesis. Furthermore, the PI hypothesizes that the function of CCK-BRi4sv in colorectal cancer biology is a direct consequence of the structural changes in the third intracellular loop domain, caused by intron retention, and the impact of those changes on intracellular signal transduction. To examine these hypotheses they plan experiments with the following specific aims: 1) to determine the spatial and temporal expression of the CCK-BR splice variant in adenomatous polyps and colon cancers; 2) to determine the effects of intron retention on receptor-mediated intracellular signal transduction and receptor desensitization/internalization; and 3) to determine the effects of ectopic expression of the CCK-BR splice variant on colonic epithelial cell homeostasis and susceptibility to carcinogen-induced colon cancer using a transgenic mouse model. These studies will provide important and new information regarding the role of the novel receptor splice variant and G-17 and G-Gly in epithelial cell biology and colon carcinogenesis. Furthermore, these studies may, in the future, provide the basis for the development of innovative therapeutic strategies for the treatment of peptide hormone-sensitive cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SURFACE PROTEIN ANCHORING IN GRAM-POSITIVE BACTERIA Principal Investigator & Institution: Schneewind, Olaf; Professor; Molecular Genetics & Cell Biol; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-JAN-2005 Summary: (Adapted from the Applicant's Abstract): Human infections caused by Grampositive bacteria present a serious therapeutic challenge due to the appearance of antibiotic-resistant strains. Of particular concern is Staphylococcus aureus,
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Staphylococcus epidermidis, and Enterococcus faecalis, Gram-positive organisms that are the most common cause of bacterial infections in American hospitals. These nosocomial pathogens have developed resistance mechanisms to all known antibiotic regimens and the development of novel targets for antimicrobial therapy is urgently needed. Surface proteins of Gram-positive organisms fulfill many important functions during the pathogenesis of human infections. This proposal describes the mechanism for surface protein anchoring in Gram-positive bacteria, which may serve as a target for antibacterial therapy. Staphylococcal surface proteins harbor a C-terminal sorting signal that functions first to retain polypeptides within the secretory pathway. Retention is followed by cleavage of the sorting signal between the threonine (T) and the glycine (G) of the LPXTG motif. The carboxyl of threonine is subsequently amide linked to the free amino group of peptidoglycan crossbridges, thereby anchoring the C-terminal end of surface proteins to the staphylococcal cell wall. Sortase, a membrane anchored enzyme of S. aureus, catalyzes a transpeptidation reaction, capturing cleaved surface protein as a thioester intermediate at the active site sulfhydryl. Nucleophilic attack of the amino group of pentaglycine crossbridges resolves the thioester intermediate, resulting in cell wall anchored surface protein and in regeneration of enzyme sulfhydryl. The elements and enzymes of surface protein anchoring, i.e., the LPXTG motif, the amino groups of peptidoglycan as well as sortase, are conserved in Gram-positive bacteria. This, we propose that surface protein anchoring is a universal mechanism. To test this hypothesis, we will characterize sortase function in S. aureus, E. faecalis and L. monocytogenes. Further, we propose identification of the peptidoglycan substrate of the sortase reaction, using in vivo labeling techniques as well as biochemical characterization of sorting intermediates in S. aureus, E. faecalis and L. monocytogenes. A genetic screen for S. aureus mutants defective in the retention step of surface protein anchoring will identify missing components of the cell wall sorting machinery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNAPTIC INTERACTIONS AND MECHANISMS IN THE RETINA Principal Investigator & Institution: Copenhagen, David R.; Professor; Ophthalmology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-FEB-1977; Project End 31-JAN-2004 Summary: The overall goal of the research is to determine how light-evoked signals in the retina are formed and how they are modified by neural activity. The neural image of the visual scene that is processed by the retina and conducted to brain is the result of a complex interplay between excitation and inhibition. One source of inhibition in the retina is the input from horizontal cells onto photoreceptors and bipolar cells; another source is the input from glycinergic and GABAergic amacrine cells onto ganglion cells. In this proposed study the focus will be on characterizing the generation and modulation of inhibitory activity in these two pathways. The general approach is to characterize first the pharmacological and biophysical bases of cell-cell interactions and then incorporate these mechanisms into a more general model. For horizontal cells the study will be directed to investigating the mechanisms by which extracellular neurotransmitters, such as glutamate and GABA, and intracellular second messengers, particularly H+ ions, regulate function. For ganglion cells this project will characterize the action and mechanisms of glycinemediated inhibition in the tiger salamander and mouse retina. The study will utilize patch pipettes to perform voltage-clamp measurements from enzymatically-isolated retinal neurons. These same recording techniques will be used to measure light-evoked responses from neurons in the retinal
50
Glycine
slice preparation. Intracellular H+ and calcium ion activities will be monitored optically with selective dyes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SYNTHESIS OF HOMOCHIRAL BETA-BRANCHED-CHAIN AMINO ACIDS Principal Investigator & Institution: Kilgore, James L.; Biocatalytics, Inc. Suite 103 Pasadena, Ca 91106 Timing: Fiscal Year 2004; Project Start 01-AUG-2004; Project End 31-JAN-2005 Summary: (provided by applicant): Many nonproteogenic amino acids have proved useful for inhibiting biodegradation and improving biological activity in peptides and peptidomimetic drugs. Few non-genetically encoded branched-chain amino acids (BCAAs) are commercially available, despite the importance of BCAA side-chain interactions in determining polypeptide structure. Chiral branches permit fine-tuning of biological activity by subtly changing side-chain shapes. For example, D-isoleucine substitution gives more specific and effective insulin and vasopressin antagonists, and potent short antiangiogenic peptides. Branch-carbon configurations of beta-methyl arylamino acids strongly affect activity. Thus beta-chiral BCAAs can provide better models for bioactive polypeptide conformations and greatly improve both activity and duration of action in peptide therapeutics. Most syntheses of beta-chiral BCAAs begin by stereorandomly building carbon skeletons, then separating diastereomers and finally enantiomers. In the case of D-alloisoleucine, numerous attempts to improve on this inefficient synthetic strategy have only resulted in expensive, complex processes which are difficult to scale up. Interest in less-common branched-chain amino acids is high, but commercial sources are currently not providing the quantities needed for drug development at acceptable cost. In developing a scalable enzymatic process to cleanly isomerize L-Ile to D-allo-Ile, we realized that obtaining amino acid frameworks with the correct side-chain branch configuration is the crucial problem in making any betabranched BCAA, because stereo directed epimerizations can quantitatively convert alpha-isomeric mixtures to homochiral )roducts. We will compare the synthetic and economic merits of straightforward glycine anion alkylations with two novel cyclopropane ring-opening procedures for making amino acids with beta-chiral branches. alpha-Carbon epimers will then be made uniformly D- or L- by wellprecedented chemoenzymatic processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: THE BEHAVIORAL PHARMACOLOGY OF PHENCYCLIDINE Principal Investigator & Institution: Balster, Robert L.; Professor; Pharmacology and Toxicology; Virginia Commonwealth University Richmond, Va 232980568 Timing: Fiscal Year 2002; Project Start 01-APR-1976; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's Abstract) The abuse of phencyclidine (PCP) and ketamine remain important public health problems, yet relatively less basic scientific information is available on this class of drugs than some other, more widely studied, abused drugs. One goal of our research is to continue to advance our understanding of the pharmacology of this class of PCP-like drugs. In previous years of this project, we have shown that PCP-like drugs functioned as antagonists of the Nmethyl-D-aspartate (NMDA) subtype of glutamate receptor to produce behavioral effects in animals that are relevant to their abuse potential. NMDA antagonists are possible treatments for drug tolerance and dependence. Other important indications for
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NMDA antagonists include use for treatment of epilepsy, head injury and stroke, anxiety and panic disorders and pain. Thus, another significant goal of our work is to provide scientific information that can lead to the development of medications that have diminished capacity for PCP-like psychological effects and abuse liability. Our strategy for doing this is to compare the behavioral pharmacology of NMDA antagonists that act at various sites on the NMDA receptor complex, including PCP-site channel blockers which vary in affinity and other important characteristics, competitive antagonists, glycine-site antagonists, polyamine-site antagonists as well as NMDA receptor subtype selective agents using well validated animal testing procedures in rats and rhesus monkeys. These types of drugs will be compared using 1) Drug discrimination in rats and rhesus monkeys using NMDA antagonists as training drugs, 2) Drug vs. drug discrimination in rats and rhesus monkeys to further differentiate similar drug effects identified in drug vs. no-drug discrimination, 3) Intravenous drug self-administration in rhesus monkeys, 4) Drug discrimination in rats using novel GABAergic drugs, 5) Tests for anti-anxiety effects using a multiple drug discrimination-punished responding schedule in rats, and 6) Tests for effects on the efficacy of intravenous cocaine reinforcement in rhesus monkeys using a procedure which will also allow assessment of effects on conditioned reinforcement which might be involved in cocaine craving. This latter study is part of a planned continued collaboration with scientists at the Pavlov Medical University in St. Petersburg supported under a Fogerty Center grant tied to this project. Finally, the hypothesis that subtypes of NMDA receptors comprised of NR2A subunits are important for mediating PCP discrimination will be tested using antisense procedures directed to knocking down the expression of this and other subunits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COMPLEXES
THE
BIOLOGICAL
ACTIVITY
OF
METAL
ION-GASTRIN
Principal Investigator & Institution: Baldwin, Graham S.; University of Melbourne Parkville 3052, Australia Parkville, Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The long-term aim of this project is to understand the biological significance of the interactions between metal ions and peptides derived from the prohormone progastrin. Recent data from this laboratory has shown that progastrin-derived peptides (PDPs) selectively bind 2 ferric ions, and that recombinant human progastrin also binds a calcium ion with high affinity, at a site distinct from the ferric ion binding site. The specific aims of the project are: (1) to define the properties and structure of the complexes between metal ions and PDPs, (2) to define the role of metal ions in the biological activities of PDPs including receptor binding, cell proliferation and cell migration, and (3) to determine the role of the complexes in modulation of progastrin processing and in metal ion uptake by the gastrointestinal tract. The health significance of the project lies in the facts that PDPs act as growth factors for the normal gastric and colonic mucosa, accelerate the development of both gastric and colorectal cancer, and may be involved in disorders of iron homeostasis. The research design mirrors the specific aims. Firstly, the structures of the complexes between metal ions and PDPs will be determined by a combination of fluorescence, EPR and NMR spectroscopy. The structures will be used as the basis for the design of recombinant and synthetic PDPs with single amino acid substitutions which prevent the binding of either ferric or calcium ions. Secondly, the ability of the parent and mutant PDPs to bind to, stimulate proliferation in, and reduce adhesion of, a panel of gastrointestinal cell lines will be compared. Proliferation will be assessed by
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Glycine
measurement of DNA synthesis in cell lines, isolated crypts, and the defunctioned colon in vivo. Adhesion will be assessed by immunochemical analysis of adhesion protein complexes, and migration and wound healing assays in tissue culture. Thirdly, the effect of changes in ferric ion concentration on progastrin processing will be measured in cell lines and in mice with altered iron status. The role of PDPs in the cellular uptake of ferric ions will also be determined. The demonstration that ferric and calcium ions are essential components of the biologically active forms of PDPs would alter completely our understanding of the role of metal ions in hormone function. The studies may also reveal an unexpected role for peptide hormones in ferric ion homeostasis. In the longer term definition of high affinity receptors for PDP-metal ion complexes may permit the development of novel therapies for treatment of disorders of iron metabolism and of gastrointestinal cancers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE MULTIFUNCTIONAL PROTEIN GEPHYRIN Principal Investigator & Institution: Schindelin, Hermann; Biochemistry and Cell Biology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The synapse represents a specialized structure for communication between neurons in the central nervous systems. Members of the ligand-gated ion channel superfamily of neurotransmitter receptors are responsible for rapid transmission of excitatory and inhibitory signals at synaptic sites and their localization at postsynaptic sites is vital for efficient synaptic transmission. The postsynaptic sites are characterized by dense accumulations of submembranous cytoskeletal elements. The mammalian protein gephyrin is crucial for the clustering of inhibitory glycine and GABAA receptors. Gephyrin anchors glycine receptors to the cytoskeleton through simultaneous binding to the 13-subunit of the receptor and tubulin. In addition, gephyrin interacts with other proteins presumably playing important roles in the assembly of postsynaptic densities, including collybistin, RAFT1, profilin and GABARAP. Gephyrin has been postulated to form a hexagonal scaffold underneath the postsynaptic membrane, which provides binding sites for the receptors and elements of the cytoskeleton. The overall goal of this proposal is to evaluate and expand this scaffolding model. One underlying hypothesis is that the functions of gephyrin pertaining to the organization of the postsynaptic membrane are distributed throughout its primary sequence and are not only confined to the linker region as has been generally assumed. This strategy would allow gephyrin to simultaneously engage in multiple binding interactions, thus modulating the activities of several of its binding partners. A second hypothesis of this proposal is that binding of the partner proteins influences the oligomeric state of gephyrin and consequently its ability to form the hexagonal scaffold underneath the postsynaptic membrane. In order to investigate the scaffolding model, gephyrin as well as its complexes will be analyzed by biochemical and crystallographic techniques in order to understand its functional diversity. Specifically, the proposal will identify regions in gephyrin responsible for recognition of its binding partners. The strengths of the protein-protein complexes and their oligomeric states will be analyzed by biophysical techniques. These studies will be complemented by crystal structure analyses of full-length gephyrin, its E-domain and the various protein-protein complexes formed by this protein. These experiments will advance the understanding of the multiple functions of gephyrin in organizing the postsynaptic membrane at inhibitory synapses and will test and extend the scaffolding model of gephyrin.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT IMPAIRMENTS
OF
NEGATIVE
SYMPTOMS
&
COGNITIVE
Principal Investigator & Institution: Carpenter, William T.; Director; Psychiatry; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 15-JAN-2000; Project End 31-DEC-2003 Summary: The present proposal is a four site multi-center study designed to assess the efficacy of the glutamatergic agents, d-cycloserine and glycine, for the treatment of persistent negative symptoms and cognitive impairments in patients with schizophrenia. These manifestations of schizophrenia account for much of the long-term morbidity, impaired social and occupational functioning, and poor quality of life observed in patients with schizophrenia. Persistent negative symptoms may either by primary (deficit symptoms) or secondary. A present, conventional and novel antipsychotics have limited efficacy for secondary negative symptoms, and there are no known effective treatments for deficit symptoms. There are also no known agents with robust efficacy for cognitive impairments. The long-term objective of this application is to develop an effective treatment for persistent negative symptoms, both primary and secondary and cognitive impairments. The Specific Aims are to examine whether: 1) decycloserine and/or glycine is superior to placebo for the treatment of persistent primary and secondary negative symptoms; and 2) d- cycloserine and/or glycine is superior to placebo in the treatment of persistent primary secondary and secondary negative symptoms, and 2) d- cycloserine and/or glycine is superior to placebo in the treatment of cognitive impairments in deficit and non-deficit patients. Secondary goals include: a) to establish a standard clinical trial methodology to assess the therapeutic efficacy of potential treatments of persistent negative symptoms and cognitive impairments.; and b) to describe the relationship between cognitive impairments, as assessed by neuropsychological test performance, and negative symptoms in the clinical trial context. The study will be a 16 double-blind parallel groups comparison of adjunctive medication (i.e., trial context) The study will be a 16 week double-blind, parallel groups comparison of adjunctive medication (i.e., d-cylcoserine and glycine) and placebo. Neuropsychological tests will be used to assess cognitive functioning, and will be administered at baseline and at the end of the study. The study will provide new information on the efficacy of d- cyclosporine and glycine for both persistent primary and secondary negative symptoms and its effect on cognitive functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF NEGATIVE SYMPTOMS AND COGNITIVE IMPAIRMENTS Principal Investigator & Institution: Schooler, Nina R.; Director; Long Island Jewish Medical Center 270-05 76Th Ave New Hyde Park, Ny 11040 Timing: Fiscal Year 2002; Project Start 15-JAN-2000; Project End 31-DEC-2003 Summary: The present proposal is a resubmission of 1R01 MH59784-01, "Treatment of Negative Symptoms and Cognitive Impairments," a four site multicenter application designed to assess the efficacy of the glutamatergic agents, d-cycloserine and glycine, for the treatment of persistent negative symptoms and cognitive impairments in patients with schizophrenia. These manifestations of schizophrenia account for much of the long-term morbidity, impaired social and occupational functioning, and poor quality of life observed in patients with schizophrenia. Persistent negative symptoms may either
54
Glycine
be primary (deficit symptoms) or secondary. At present, conventional and novel antipsychotics have limited efficacy for secondary negative symptoms, and there are no known effective treatments for these deficit symptoms. There are also no known agents with robust efficacy for cognitive impairments. The long-term objective of this application is to develop an effective treatment for persistent negative symptoms, both primary and secondary, and cognitive impairments. The Specific Aims are to examine whether: 1) d-cycloserine and/or glycine is superior to placebo for the treatment of persistent primary and secondary negative symptoms; and 2) d-cycloserine and/or glycine is superior to placebo in the treatment of cognitive impairments in deficit and nondeficit patients. Secondary goals include: a) to establish a standard clinical trial methodology to assess the therapeutic efficacy of potential treatments of persistent negative symptoms and cognitive impairments; and b) to describe the relationship between cognitive impairments, as assessed by neuropsychological test performance, and negative symptoms in the clinical trial context. The study will be a 16-week doubleblind, parallel groups comparison of adjunctive medication (i.e., d-cycloserine and glycine) to placebo. Neuropsychological tests will be used to assess cognitive functioning, and will be administered at baseline and at the end of the study. The study will provide new information on the efficacy of d-cycloserine and glycine for both persistent primary and secondary negative symptoms and theirs effects on cognitive functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USE DEPENDENT PLASTICITY OF SPINAL INHIBITION Principal Investigator & Institution: Tillakaratne, Niranjala; Physiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2004; Project Start 15-APR-2002; Project End 31-MAR-2007 Summary: Both experimental animals and humans can regain the ability to stand or to step after a complete spinal cord transection. The ability to execute these tasks depends on specific training regimens, illustrating the importance of motor leading in the spinal cord. Low-thoracic transection and subsequent training leads to a persistent increase in the total inhibitory capacity of the lumbar spinal cord, exhibited by increases in GAD67, a GABA-synthesizing enzyme, and its mRNA, as well as in the alpha-1 subunit of glycine receptor and in gephyrin, a protein associated with glycine receptors. However, repetitive hindlimb training, such as stepping, returns the levels of GAD67 and glycine receptors towards normal. The central hypothesis of this proposal is that task-specific, repetitive training selectively modulates the inhibition within sensorimotor pathways associated with the execution of that task. Using a robotic device, we will test this hypothesis with a well-defined standing task in neonatally transected (T12-13) rats. Stand training allows us to compare training-induced changes in neurons associated with plantarflexion (facilitation of the soleus motor pool) and neurons associated with dorsiflexion (inhibition of the tibialis anterior motor pool). We will test three hypotheses: (1) that stand training decreases the inhibitory capacity of specific neurons associated with the ankle dorsiflexor (tibialis anterior); (2) that training selectively alters the ratio of inhibitory and excitatory synapses on the somata of individual motoneurons in motor pools associated with soleus, and (3) that pharmacologically induced changes in motor performance of spinally transected rats reflect these alterations in GABAergic and glycinergic inhibition in plantarflexion- and dorsiflexor-associated neurons as noted in the first two hypotheses. A major innovation in this work is the ability to train motor tasks, and to quantify the kinematics of standing and stepping using a newly developed
Studies
55
robotic device. This device will allow us to impose strictly repetitive training and to assess the progress of individual animals with great precision. The proposed studies address the anatomical and molecular bases of the plasticity that may underlie rehabilitative training after spinal injury. This work will lead to better ways of testing the effectiveness of alternative training strategies and associated pharmacological interventions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: USE OF HAMMERHEAD RIBOZYMES IN MURINE MODELS OF OL Principal Investigator & Institution: Wenstrup, Richard J.; Professor; Children's Hospital Med Ctr (Cincinnati) 3333 Burnet Ave Cincinnati, Oh 452293039 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The overall goal of these studies is to test the ability of self-cleaving multimeric ribozyme constructs to ameliorate phenotypic features of osteogenesis imperfecta (OI). We propose that the dominant-negative effect of "structural" or non-excluded type I collagen mutations associated with the most severe forms of OI must be taken into account in all strategies aimed at correcting the collagen defects in those patients, and that elimination of mutant alleles must be highly efficient, since even low levels of mutant allelic products can have a major deleterious effect. Experiments described in this proposal are designed to advance our development of ribozyme genes that effectively target type I collagen mutations typically observed in severe OI patients. In particular, self-cleaving multimeric ribozyme expressing genes will be designed and tested. These may provide sufficiently high ribozyme delivery to target cells so that a greater degree of allelic selectivity can be designed into ribozyme subunits that would ultimately be targeted against heterozygous single nucleotide substitutions. Experiments described in this proposal include: (1) design and testing of self-cleaving multimeric hammerhead ribozyme(s) that selectively cleave adjacent to a unique deletion junction in the human proa1(I) collagen minigene pMG155. Preliminary testing of the ribozymes' efficiency will be performed by RNase protection in vitro. Target constructs will be stably expressed in MC3T3-E1 cells for in cellulo ribozyme testing. Cleavage efficacy and reversal of a well-defined biochemical phenotype in minigene-expressing MC3T3-E1 cells will be demonstrated by Northern and Western blot analysis, pulse-chase labeling of procollagens, and measurement of several markers of cellular differentiation. Transgenic mice that express either pMG155 or the most optimal multimeric ribozyme expression gene will be mated, and the phenotypes of doubly transgenic mice will be compared to those of mice expressing only the target sequence or the ribozyme; (2) similar in vitro, in cellulo, and in vivo testing will be performed on multimeric ribozymes, that target glycine mutations created in modified versions pMG155 containing an in-frame, 270 bp eDNA segment from the 3' end of the triple helical domain of the murine colla2 gene; and (3) we will test possible additive therapeutic benefits of targeting a potential downstream mediator of the OI dominant negative phenotype, osteocalcin, in mice transgenic for a collagen minigene and optimal ribozyme construct targeting both the minigene and osteocalcin. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: USING CHEMICAL GENETICS TO EXPLORE GROEL FUNCTION Principal Investigator & Institution: Chapman, Eli; Genetics; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2007
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Glycine
Summary: (provided by applicant): The chaperonin GroEL in the bacterial cytoplasm has been shown to assist polypeptide chain folding but to date, a strain severely conditionally deficient in GroEL has not been available. Such a strain would allow one to address such questions as: do GroEL-deficient cells continue to translate polypeptides? How many and which polypeptides become misfolded/aggregated under such conditions? Are inclusion bodies formed? Are other chaperones induced? Here we propose to attack this problem by producing a chemical inhibitor that will cross E. coli membranes and immediately shut off the ATPase of a mutationally sensitized GroEL, blocking chaperonin action. Based on molecular modeling studies, we have selected two residues in the ATP pocket, Asn479 and Ite493, to mutate to smaller residues, alanine and glycine, to create a hydrophobic pocket potentially capable of binding one or more of a chemically synthesized series of adenine analogues with large, hydrophobic groups attached at various positions. The combination of the sensitized GroEL mutant and cell permeable inhibitor should allow for the rapid and severe inhibition of GroEL function in vivo. We will then assay protein translation, protein folding, and cell morphology of E. coli cells expressing the sensitized GroEL mutant. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VIBRATIONAL STUDIES OF ENERGY TRANSDUCING PROTEINS Principal Investigator & Institution: Bocian, David F.; Professor; Chemistry; University of California Riverside 900 University Ave Riverside, Ca 92521 Timing: Fiscal Year 2002; Project Start 01-JUL-1988; Project End 31-JUL-2004 Summary: The specific aims of the proposed research are to characterize the structural, vibronic, and electronic properties of the functionally important cofactors in reaction center (RC) proteins. The principal investigative tool is resonance Raman (RR) spectroscopy. The first major objective is to characterize the properties of the bacteriochlorophyll/bacteriopheophytin (BCh1/BPh) in genetically modified bacterial RCs that exhibit unusual electron-transfer properties. The genetic modifications include replacements near the primary electron donor (P), both accessory BChls, and the BPh on the photophysically, active L branch of the protein (which is the primary electron acceptor). The studies focus on three general classes of genetically modified RCs: (1) Mutants in which the hydrogen bonding interactions and/or the electric fields in the vicinity of BCh1L, BCh1M, and BPhL are altered by addition/deletion of amino acid residues near ring V of the BCh1/BPh macrocycle. A particular focus of these studies concerns the effects of placing (potentially) charged residues near the photoactive cofactors. (2) Double (and higher order) mutants which incorporate the replacements characteristic of class 1 into a background in which BPhL is replaced with a BCh1 molecule (beta-type RCs). (3) Mutants in which the histidine axial ligands to the BChls of P are replaced by non-ligating glycine residues (cavity mutants). In all cases the RR studies will be conducted on RCs whose detailed electron-transfer kinetics have been elucidated via time-resolved optical experiments. The second major objective is to conduct RR studies aimed at refining the structure of oxygen- evolving complex in photosystem (PS) II RCs. The particular target of these studies is the manganese cluster, which directly mediates the water-splitting/oxygen-evolution reaction. The focus will be the low-frequency region of the spectrum where manganese-ligand vibrations are expected to occur. Toward this end, RR data will be acquired for PSII in which isotopic labels (2H, 18O, 15N, 37C1-/37C1- ) have been incorporated and/or essential ions such as Ca+2 and C1- have been exchanged (for example, Sr+2 for Ca+2 or Br- for C1-). The long-term objective of the studies on bacterial and PSII RCs is to determine how the physical properties of the cofactors (structure, conformation, electron-density
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57
distribution) govern and/or reflect their functional characteristics (electron transfer/charge separation across the biological membrane; water splitting/oxygen evolution). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: X-RAY DIFFRACTION STUDIES OF OLIGOPEPTIDES Principal Investigator & Institution: Karle, Isabella L.; U.S. Naval Research Laboratory 4555 Overlook Ave Sw Washington, Dc 20375 Timing: Fiscal Year 2004; Project Start 01-AUG-1982; Project End 31-MAY-2008 Summary: (provided by applicant): The aim of the proposed research is to determine the three-dimensional structure of a number of peptides (10-30 residues) that perform a variety of functions such as ion transport, analgesia, toxic, antitoxic and antibiotic by means of single crystal X-ray diffraction analysis. These crystals are composed of molecules containing light atoms only, C, N, O and H. The method of solution will be direct phase determination using the tangent formula and a variety of auxiliary formulas. Goals are to continue to design peptide sequences, with a concentration on the production of individual molecules that contain several domains, such as helix/helix reversal/beta sheet. Additional goals are to design beta sheets composed of multiple strands. Considerable success in design, crystallization and structure determination has already been achieved in this laboratory with multiple domains and a variety of betasheets. Another area in which effects on conformation are being studied is the insertion or substitution of unusual amino acid residues into a sequence. The unusual amino acid residues already used, or to be used, occur naturally in the lower forms of life (fungi, parasites, bacteria, e.g.) The helix inducing propensity of the Aib residue (dimethyl glycine) has been widely explored in this laboratory in designed peptides, as well as in naturally occurring peptides such as the ionophores antiamoebin and zervamicin, during the current grant period. The emphasis is now turning to beta peptides incorporated into beta-hairpins. The resulting beta-sheets acquire a polarity which is not present in peptides with all alpha-amino residues. Further, the serendipitous formation of hydrophobic pores with diameters >10 Angstroms, by the assembly of 19-mer helices that contain three D-residues, merits further study of both the right-handed helix formation of sequences with so many D-residues and the formation of pores large enough to accommodate and possibly deliver small to medium sized drug molecules. Among X-ray quality crystals on hand are peptides with gamma-amino residues and some with probable multi-stranded beta sheets. 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
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.
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Glycine
unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “glycine” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for glycine in the PubMed Central database: •
13C nuclear magnetic resonance detection of interactions of serine hydroxymethyltransferase with C1-tetrahydrofolate synthase and glycine decarboxylase complex activities in Arabidopsis. by Prabhu V, Chatson KB, Abrams GD, King J.; 1996 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=157939
•
7-Chlorokynurenic acid is a selective antagonist at the glycine modulatory site of the N-methyl-D-aspartate receptor complex. by Kemp JA, Foster AC, Leeson PD, Priestley T, Tridgett R, Iversen LL, Woodruff GN.; 1988 Sep; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=282010
•
A glycine to serine polymorphism in the C-propeptide of the human type II procollagen. by Vissing H, Rasmussen M, D'Alessio M, Lee B, Dobkin C, Ramirez F.; 1990 Jun 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=330985
•
A lethal variant of osteogenesis imperfecta has a single base mutation that substitutes cysteine for glycine 904 of the alpha 1(I) chain of type I procollagen. The asymptomatic mother has an unidentified mutation producing an overmodified and unstable type I procollagen. by Constantinou CD, Nielsen KB, Prockop DJ.; 1989 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=303717
•
A possible glycine radical in anaerobic ribonucleotide reductase from Escherichia coli: nucleotide sequence of the cloned nrdD gene. by Sun X, Harder J, Krook M, Jornvall H, Sjoberg BM, Reichard P.; 1993 Jan 15; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=45706
•
A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3. by Methot N, Song MS, Sonenberg N.; 1996 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=231531
•
Active transport of gamma-aminobutyric acid and glycine into synaptic vesicles. by Kish PE, Fischer-Bovenkerk C, Ueda T.; 1989 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=287244
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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An osteopenic nonfracture syndrome with features of mild osteogenesis imperfecta associated with the substitution of a cysteine for glycine at triple helix position 43 in the pro alpha 1(I) chain of type I collagen. by Shapiro JR, Stover ML, Burn VE, McKinstry MB, Burshell AL, Chipman SD, Rowe DW.; 1992 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442889
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Antagonism of ligand-gated ion channel receptors: two domains of the glycine receptor alpha subunit form the strychnine-binding site. by Vandenberg RJ, French CR, Barry PH, Shine J, Schofield PR.; 1992 Mar 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=48533
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Biosynthesis of the Pyrimidine Moiety of Thiamine Independent of the PurF Enzyme (Phosphoribosylpyrophosphate Amidotransferase) in Salmonella typhimurium: Incorporation of Stable Isotope-Labeled Glycine and Formate. by Enos-Berlage JL, Downs DM.; 1999 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=93450
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Characterization of Glycine Betaine Porter I from Listeria monocytogenes and Its Roles in Salt and Chill Tolerance. by Mendum ML, Smith LT.; 2002 Feb; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=126668
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Characterization of Glycine Sarcosine N-Methyltransferase and Sarcosine Dimethylglycine N-Methyltransferase. by Nyyssola A, Reinikainen T, Leisola M.; 2001 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=92834
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Chicken T-cell receptor beta-chain diversity: an evolutionarily conserved D betaencoded glycine turn within the hypervariable CDR3 domain. by McCormack WT, Tjoelker LW, Stella G, Postema CE, Thompson CB.; 1991 Sep 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=52369
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Cloning, expression, and localization of a rat brain high-affinity glycine transporter. by Guastella J, Brecha N, Weigmann C, Lester HA, Davidson N.; 1992 Aug 1; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=49671
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Cross-Reactivity of Epstein-Barr Virus-Specific Immunoglobulin M Antibodies with Cytomegalovirus Antigens Containing Glycine Homopolymers. by Lang D, Vornhagen R, Rothe M, Hinderer W, Sonneborn HH, Plachter B.; 2001 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96137
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Cytoprotective effects of glycine and glutathione against hypoxic injury to renal tubules. by Weinberg JM, Davis JA, Abarzua M, Rajan T.; 1987 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=442402
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Defective glycine cleavage system in nonketotic hyperglycinemia. Occurrence of a less active glycine decarboxylase and an abnormal aminomethyl carrier protein. by Hiraga K, Kochi H, Hayasaka K, Kikuchi G, Nyhan WL.; 1981 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=370827
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Dietary Glycine Prevents Peptidoglycan Polysaccharide-Induced Reactive Arthritis in the Rat: Role for Glycine-Gated Chloride Channel. by Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG.; 2001 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=98707
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Direct Observation of Better Hydration at the N Terminus of an [alpha]- Helix with Glycine Rather than Alanine as the N-Cap Residue. by Harpaz Y, Elmasry N, Fersht AR, Henrick K.; 1994 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42937
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Discrimination of heterogenous mRNAs encoding strychnine-sensitive glycine receptors in Xenopus oocytes by antisense oligonucleotides. by Akagi H, Patton DE, Miledi R.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=298223
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DNA sequence and characterization of GcvA, a LysR family regulatory protein for the Escherichia coli glycine cleavage enzyme system. by Wilson RL, Stauffer GV.; 1994 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=205440
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d-Serine is an endogenous ligand for the glycine site of the N-methyl-d-aspartate receptor. by Mothet JP, Parent AT, Wolosker H, Brady RO Jr, Linden DJ, Ferris CD, Rogawski MA, Snyder SH.; 2000 Apr 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=18334
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Effect of exogenous glycine on peptidoglycan composition and resistance in a methicillin-resistant Staphylococcus aureus strain. by de Jonge BL, Chang YS, Xu N, Gage D.; 1996 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=163356
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Effect of substitution of glycine for arginine at position 146 of the A1 subunit on biological activity of Escherichia coli heat-labile enterotoxin. by Okamoto K, Okamoto K, Miyama A, Tsuji T, Honda T, Miwatani T.; 1988 May; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=211108
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Effects of Penicillin and Glycine on Cell Wall Glycopeptides of the Two Varieties of Vibrio fetus. by Fung PH, Winter AJ.; 1968 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=252519
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Effects of Sulfanilamide and Methotrexate on 13C Fluxes through the Glycine Decarboxylase/Serine Hydroxymethyltransferase Enzyme System in Arabidopsis. by Prabhu V, Brock Chatson K, Lui H, Abrams GD, King J.; 1998 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=35151
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Enhanced Virulence Mediated by the Murine Coronavirus, Mouse Hepatitis Virus Strain JHM, Is Associated with a Glycine at Residue 310 of the Spike Glycoprotein. by Ontiveros E, Kim TS, Gallagher TM, Perlman S.; 2003 Oct 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=228498
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femA, which encodes a factor essential for expression of methicillin resistance, affects glycine content of peptidoglycan in methicillin-resistant and methicillin-susceptible
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Staphylococcus aureus strains. by Maidhof H, Reinicke B, Blumel P, Berger-Bachi B, Labischinski H.; 1991 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=207965 •
Genetic and Physiological Control of Serine and Glycine Biosynthesis in Saccharomyces. by Ulane R, Ogur M.; 1972 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=247248
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Glutamic acid codon suppressors derived from a unique species of glycine transfer ribonucleic acid. by Murgola EJ, Bryant JE.; 1980 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=293916
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Identification and Analysis of Genes Involved in Anaerobic Toluene Metabolism by Strain T1: Putative Role of a Glycine Free Radical. by Coschigano PW, Wehrman TS, Young LY.; 1998 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106210
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Identification of an ATP-Driven, Osmoregulated Glycine Betaine Transport System in Listeria monocytogenes. by Ko R, Smith LT.; 1999 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=99739
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Influence of a glycine or proline substitution on the functional properties of a 14amino-acid analog of Escherichia coli heat-stable enterotoxin. by Waldman SA, O'Hanley P.; 1989 Aug; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=313463
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Influence of growth conditions on glycine reductase of Clostridium sporogenes. by Venugopalan V.; 1980 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=293607
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Inhibition of the glycine decarboxylase multienzyme complex by the host-selective toxin victorin. by Navarre DA, Wolpert TJ.; 1995 Apr; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=160796
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Interaction of selenoprotein PA and the thioredoxin system, components of the NADPH-dependent reduction of glycine in Eubacterium acidaminophilum and Clostridium litorale [corrected]. by Dietrichs D, Meyer M, Rieth M, Andreesen JR.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208342
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Lack of sugar discrimination by human Pol [micro] requires a single glycine residue. by Ruiz JF, Juarez R, Garcia-Diaz M, Terrados G, Picher AJ, Gonzalez-Barrera S, Fernandez de Henestrosa AR, Blanco L.; 2003 Aug 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=169901
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Lipoic acid metabolism in Escherichia coli: isolation of null mutants defective in lipoic acid biosynthesis, molecular cloning and characterization of the E. coli lip locus, and identification of the lipoylated protein of the glycine cleavage system. by Vanden Boom TJ, Reed KE, Cronan JE Jr.; 1991 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=208974
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l-Serine and glycine serve as major astroglia-derived trophic factors for cerebellar Purkinje neurons. by Furuya S, Tabata T, Mitoma J, Yamada K, Yamasaki M, Makino A, Yamamoto T, Watanabe M, Kano M, Hirabayashi Y.; 2000 Oct 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17234
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Mode of Action of Glycine on the Biosynthesis of Peptidoglycan. by Hammes W, Schleifer KH, Kandler O.; 1973 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=285483
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Modulation of N-methyl-d-aspartate receptor function by glycine transport. by Bergeron R, Meyer TM, Coyle JT, Greene RW.; 1998 Dec 22; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28112
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Molecular basis of adult-onset and chronic GM2 gangliosidoses in patients of Ashkenazi Jewish origin: substitution of serine for glycine at position 269 of the alpha-subunit of beta-hexosaminidase. by Paw BH, Kaback MM, Neufeld EF.; 1989 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=286923
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Monoclonal antibodies and peptide mapping reveal structural similarities between the subunits of the glycine receptor of rat spinal cord. by Pfeiffer F, Simler R, Grenningloh G, Betz H.; 1984 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=392111
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Mutation of NH2-terminal glycine of p60src prevents both myristoylation and morphological transformation. by Kamps MP, Buss JE, Sefton BM.; 1985 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=390438
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Mutation of proline-1003 to glycine in the epidermal growth factor (EGF) receptor enhances responsiveness to EGF. by Schuh SM, Newberry EP, Dalton MA, Pike LJ.; 1994 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=301092
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Nucleotide insertion in the anticodon loop of a glycine transfer RNA causes missense suppression. by Prather NE, Murgola EJ, Mims BH.; 1981 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=349276
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Nucleotide sequence of wild-type and mutant nifR4 (ntrA) genes of Rhodobacter capsulatus: identification of an essential glycine residue. by Alias A, Cejudo FJ, Chabert J, Willison JC, Vignais PM.; 1989 Jul 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318117
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One Hundred Seventy-Fold Increase in Excretion of an FV Fragment-Tumor Necrosis Factor Alpha Fusion Protein (sFV/TNF-[alpha]) from Escherichia coli Caused by the Synergistic Effects of Glycine and Triton X-100. by Yang J, Moyana T, MacKenzie S, Xia Q, Xiang J.; 1998 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=106785
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Osteogenesis imperfecta. The position of substitution for glycine by cysteine in the triple helical domain of the pro alpha 1(I) chains of type I collagen determines the clinical phenotype. by Starman BJ, Eyre D, Charbonneau H, Harrylock M, Weis MA, Weiss L, Graham JM Jr, Byers PH.; 1989 Oct; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329779
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Palmitoylation, Membrane-Proximal Basic Residues, and Transmembrane Glycine Residues in the Reovirus p10 Protein Are Essential for Syncytium Formation. by Shmulevitz M, Salsman J, Duncan R.; 2003 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=224572
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Peptidoglycan tripeptide content and cross-linking are altered in Enterobacter cloacae induced to produce AmpC beta-lactamase by glycine and D-amino acids. by Ottolenghi AC, Caparros M, de Pedro MA.; 1993 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=193244
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Positive regulation of the Escherichia coli glycine cleavage enzyme system. by Wilson RL, Steiert PS, Stauffer GV.; 1993 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=196242
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Purine and glycine metabolism by purinolytic clostridia. by Durre P, Andreesen JR.; 1983 Apr; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=217447
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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 scallop myosin by the regulatory light chain depends on a single glycine residue. by Jancso A, Szent-Gyorgyi AG.; 1994 Sep 13; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=44686
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RFLPs of the gene for the human glycine receptor on the X-chromosome. by Siddique T, Phillips K, Betz H, Grenningloh G, Warner K, Hung WY, Laing N, Roses AD.; 1989 Feb 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331861
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Rickettsia prowazekii requires host cell serine and glycine for growth. by Austin FE, Turco J, Winkler HH.; 1987 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=260309
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Role of increased cytosolic free calcium in the pathogenesis of rabbit proximal tubule cell injury and protection by glycine or acidosis. by Weinberg JM, Davis JA, Roeser NF, Venkatachalam MA.; 1991 Feb; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=296346
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Role of L-threonine dehydrogenase in the catabolism of threonine and synthesis of glycine by Escherichia coli. by Newman EB, Kapoor V, Potter R.; 1976 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=233149
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Simultaneous release of penicilloic acid and phenylacetyl glycine by penicillinbinding proteins 5 and 6 of Escherichia coli. by Amanuma H, Strominger JL.; 1984 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=214817
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Sodium-coupled glycine uptake by Ehrlich ascites tumor cells results in an increase in cell volume and plasma membrane channel activities. by Hudson RL, Schultz SG.; 1988 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=279528
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Specific incorporation of glycine into bacterial lipopolysaccharide. Novel function of specific transfer ribonucleic acids. by Gamian A, Krzyzaniak A, Barciszewska MZ, Gawronska I, Barciszewski J.; 1991 Nov 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329061
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Specificities of FemA and FemB for different glycine residues: FemB cannot substitute for FemA in staphylococcal peptidoglycan pentaglycine side chain formation. by Ehlert K, Schroder W, Labischinski H.; 1997 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=179711
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Substitution of an Alanine Residue for Glycine 146 in TMP Kinase from Escherichia coli Is Responsible for Bacterial Hypersensitivity to Bromodeoxyuridine. by Tourneux L, Bucurenci N, Lascu I, Sakamoto H, Briand G, Gilles AM.; 1998 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=107429
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Surface-localized glycine transporters 1 and 2 function as monomeric proteins in Xenopus oocytes. by Horiuchi M, Nicke A, Gomeza J, Aschrafi A, Schmalzing G, Betz H.; 2001 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=29277
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The 3'-Terminal Exon of the Family of Steroid and Phenol Sulfotransferase Genes is Spliced at the N-Terminal Glycine of the Universally Conserved GXXGXXK Motif that Forms the Sulfonate Donor Binding Site. by Chiba H, Komatsu K, Lee YC, Tomizuka T, Strott CA.; 1995 Aug 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41119
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The allosteric glycine site of the N-methyl-D-aspartate receptor modulates GABAergic-mediated synaptic events in neonatal rat CA3 hippocampal neurons. by Gaiarsa JL, Corradetti R, Cherubini E, Ben-Ari Y.; 1990 Jan; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=53259
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The amino-terminal fusion domain peptide of human immunodeficiency virus type 1 gp41 inserts into the sodium dodecyl sulfate micelle primarily as a helix with a conserved glycine at the micelle-water interface. by Chang DK, Cheng SF, Chien WJ.; 1997 Sep; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=191937
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The Glycine Binding Site of the N-Methyl-D-Aspartate Receptor Subunit NR1: Identification of Novel Determinants of Co-Agonist Potentiation in the Extracellular M3-M4 Loop Region. by Hirai H, Kirsch J, Laube B, Betz H, Kuhse J.; 1996 Jun 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=39183
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The glycine neurotransmitter transporter GLYT1 is an organic osmolyte transporter regulating cell volume in cleavage-stage embryos. by Steeves CL, Hammer MA, Walker GB, Rae D, Stewart NA, Baltz JM.; 2003 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=283532
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The Nucleotide in Position 32 of the tRNA Anticodon Loop Determines Ability of Anticodon UCC to Discriminate Among Glycine Codons. by Lustig F, Boren T, Claesson C, Simonsson C, Barciszewska M, Lagerkvist U.; 1993 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=46296
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The Number of Glycine Residues Which Limits Intact Absorption of Glycine Oligopeptides in Human Jejunum. by Adibi SA, Morse EL.; 1977 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=372452
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The transmembrane domain in viral fusion: Essential role for a conserved glycine residue in vesicular stomatitis virus G protein. by Cleverley DZ, Lenard J.; 1998 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19852
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The tyrT locus of Escherichia coli exhibits a regulatory function for glycine metabolism. by Michelsen U, Bosl M, Dingermann T, Kersten H.; 1989 Nov; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=210463
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Variations among glyV-derived glycine tRNA suppressors of glutamic acid codons. by Murgola EJ, Prather NE, Hadley KH.; 1978 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=222326
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WW domain-mediated interactions reveal a spliceosome-associated protein that binds a third class of proline-rich motif: The proline glycine and methionine-rich motif. by Bedford MT, Reed R, Leder P.; 1998 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27941
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with glycine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “glycine” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for glycine (hyperlinks lead to article summaries): •
A case of autism with an interstitial deletion on 4q leading to hemizygosity for genes encoding for glutamine and glycine neurotransmitter receptor sub-units (AMPA 2, GLRA3, GLRB) and neuropeptide receptors NPY1R, NPY5R. Author(s): Ramanathan S, Woodroffe A, Flodman PL, Mays LZ, Hanouni M, Modahl CB, Steinberg-Epstein R, Bocian ME, Spence MA, Smith M. Source: Bmc Medical Genetics [electronic Resource]. 2004 April 16; 5(1): 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15090072
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A GLRA1 null mutation in recessive hyperekplexia challenges the functional role of glycine receptors. Author(s): Brune W, Weber RG, Saul B, von Knebel Doeberitz M, Grond-Ginsbach C, Kellerman K, Meinck HM, Becker CM. Source: American Journal of Human Genetics. 1996 May; 58(5): 989-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8651283
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A glycine-rich region in NF-kappaB p105 functions as a processing signal for the generation of the p50 subunit. Author(s): Lin L, Ghosh S. Source: Molecular and Cellular Biology. 1996 May; 16(5): 2248-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8628291
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A mutation at glycine residue 31 of toxic shock syndrome toxin-1 defines a functional site critical for major histocompatibility complex class II binding and superantigenic activity. Author(s): Kum WW, Wood JA, Chow AW. Source: The Journal of Infectious Diseases. 1996 December; 174(6): 1261-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8940217
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A new way to prevent leakage of glycine during endoscopic transanal resection of rectal lesions. Author(s): Abbasakoor F, Stephens RB. Source: The British Journal of Surgery. 1996 October; 83(10): 1467. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8944475
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A novel effect of bismuth ions: selective inhibition of the biological activity of glycine-extended gastrin. Author(s): Pannequin J, Kovac S, Tantiongco JP, Norton RS, Shulkes A, Barnham KJ, Baldwin GS. Source: The Journal of Biological Chemistry. 2004 January 23; 279(4): 2453-60. Epub 2003 October 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14530269
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A novel glycine receptor alpha Z1 subunit variant in the zebrafish brain. Author(s): Devignot V, Prado de Carvalho L, Bregestovski P, Goblet C. Source: Neuroscience. 2003; 122(2): 449-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614909
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A novel hyperekplexia-causing mutation in the pre-transmembrane segment 1 of the human glycine receptor alpha1 subunit reduces membrane expression and impairs gating by agonists. Author(s): Castaldo P, Stefanoni P, Miceli F, Coppola G, Del Giudice EM, Bellini G, Pascotto A, Trudell JR, Harrison NL, Annunziato L, Taglialatela M. Source: The Journal of Biological Chemistry. 2004 June 11; 279(24): 25598-604. Epub 2004 April 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15066993
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A novel monoclonal antibody to N-myristoyl glycine moiety found a new Nmyristoylated HIV-1 p28gag protein in HIV-1-infected cells. Author(s): Furuishi K, Misumi S, Shoji S. Source: Biochemical and Biophysical Research Communications. 1996 May 15; 222(2): 344-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8670207
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A novel mutation (Gln266-->His) in the alpha 1 subunit of the inhibitory glycinereceptor gene (GLRA1) in hereditary hyperekplexia. Author(s): Milani N, Dalpra L, del Prete A, Zanini R, Larizza L. Source: American Journal of Human Genetics. 1996 February; 58(2): 420-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8571969
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A nucleoside diphosphate kinase A (nm23-H1) serine 120-->glycine substitution in advanced stage neuroblastoma affects enzyme stability and alters protein-protein interaction. Author(s): Chang CL, Strahler JR, Thoraval DH, Qian MG, Hinderer R, Hanash SM. Source: Oncogene. 1996 February 1; 12(3): 659-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8637723
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A recombinant, arginine-glycine-aspartic acid (RGD) motif from foot-and-mouth disease virus binds mammalian cells through vitronectin and, to a lower extent, fibronectin receptors. Author(s): Villaverde A, Feliu JX, Harbottle RP, Benito A, Coutelle C. Source: Gene. 1996 November 21; 180(1-2): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8973352
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A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3. Author(s): Methot N, Song MS, Sonenberg N. Source: Molecular and Cellular Biology. 1996 October; 16(10): 5328-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8816444
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Absorption of glycine irrigating solution during endoscopic transanal resection of rectal tumors. Author(s): Debras B, Bergamaschi R, Becouarn G, Arnaud JP. Source: Diseases of the Colon and Rectum. 1996 November; 39(11): 1245-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8918433
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Acetylsalicylic acid tablets with glycine improve long-term tolerability in antiplatelet drug therapy: results of a noninterventional trial. Author(s): Kusche W, Paxinos R, Haselmann J, Schwantes U, Breddin HK. Source: Adv Ther. 2003 September-October; 20(5): 237-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14964343
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Allergic contact dermatitis from dodecyldiaminoethyl-glycine and isopropyl alcohol in a commercial disinfectant swab. Author(s): Kwon JA, Lee MS, Kim MY, Park YM, Kim HO, Kim CW. Source: Contact Dermatitis. 2003 June; 48(6): 339-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531876
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Arachnoid cyst and chronic subdural haematoma in a child with osteogenesis imperfecta type III resulting from the substitution of glycine 1006 by alanine in the pro alpha 2(I) chain of type I procollagen. Author(s): Cole WG, Lam TP. Source: Journal of Medical Genetics. 1996 March; 33(3): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8728690
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Arg-14 loop of site 3 anemone toxins: effects of glycine replacement on toxin affinity. Author(s): Seibert AL, Liu J, Hanck DA, Blumenthal KM. Source: Biochemistry. 2003 December 16; 42(49): 14515-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14661964
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Association of gephyrin and glycine receptors in the human brainstem and spinal cord: an immunohistochemical analysis. Author(s): Baer K, Waldvogel HJ, During MJ, Snell RG, Faull RL, Rees MI. Source: Neuroscience. 2003; 122(3): 773-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622920
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Autocrine stimulation of AR4-2J rat pancreatic tumor cell growth by glycine-extended gastrin. Author(s): Negre F, Fagot-Revurat P, Bouisson M, Rehfeld JF, Vaysse N, Pradayrol L. Source: International Journal of Cancer. Journal International Du Cancer. 1996 May 29; 66(5): 653-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8647628
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Beneficial effects of glycine (bioglycin) on memory and attention in young and middle-aged adults. Author(s): File SE, Fluck E, Fernandes C. Source: Journal of Clinical Psychopharmacology. 1999 December; 19(6): 506-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10587285
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Beneficial effects of L-serine and glycine in the management of seizures in 3phosphoglycerate dehydrogenase deficiency. Author(s): de Koning TJ, Duran M, Dorland L, Gooskens R, Van Schaftingen E, Jaeken J, Blau N, Berger R, Poll-The BT. Source: Annals of Neurology. 1998 August; 44(2): 261-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9708551
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Benzoate-induced changes in glycine and urea metabolism in patients with chronic renal failure. Author(s): Mitch WE, Brusilow S. Source: The Journal of Pharmacology and Experimental Therapeutics. 1982 September; 222(3): 572-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7108765
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Bicuculline antagonizes 5-HT(3A) and alpha2 glycine receptors expressed in Xenopus oocytes. Author(s): Sun H, Machu TK. Source: European Journal of Pharmacology. 2000 March 17; 391(3): 243-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10729364
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Bile acid glycine and taurine conjugates in serum of patients with primary biliary cirrhosis: effect of ursodeoxycholic treatment. Author(s): Chretien Y, Poupon R, Gherardt MF, Chazouilleres O, Labbe D, Myara A, Trivin F. Source: Gut. 1989 August; 30(8): 1110-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2767508
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Binding of the snake venom-derived proteins applaggin and echistatin to the arginine-glycine-aspartic acid recognition site(s) on platelet glycoprotein IIb.IIIa complex inhibits receptor function. Author(s): Savage B, Marzec UM, Chao BH, Harker LA, Maraganore JM, Ruggeri ZM. Source: The Journal of Biological Chemistry. 1990 July 15; 265(20): 11766-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2365698
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Binding site stoichiometry and the effects of phosphorylation on human alpha1 homomeric glycine receptors. Author(s): Gentet LJ, Clements JD. Source: The Journal of Physiology. 2002 October 1; 544(Pt 1): 97-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12356883
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Binding to the glycine site of the NMDA receptor complex in brains of patients with Alzheimer's disease. Author(s): Del Bel EA, Slater P. Source: Neuroscience Letters. 1991 September 30; 131(1): 75-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1838796
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Bioactivity of peptide analogs of the neutrophil chemoattractant, N-acetyl-prolineglycine-proline. Author(s): Haddox JL, Pfister RR, Muccio DD, Villain M, Sommers CI, Chaddha M, Anantharamaiah GM, Brouillette WJ, DeLucas LJ. Source: Investigative Ophthalmology & Visual Science. 1999 September; 40(10): 2427-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10476813
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Bioavailability of iron glycine as a fortificant in infant foods. Author(s): Fox TE, Eagles J, Fairweather-Tait SJ. Source: The American Journal of Clinical Nutrition. 1998 April; 67(4): 664-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9537613
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Bioavailability of iron glycine. Author(s): Ashmead HD. Source: The American Journal of Clinical Nutrition. 1999 April; 69(4): 737-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197576
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Biochemical hemodynamic and hematological changes during transcervical resection of the endometrium using 1.5% glycine as the irrigating solution. Author(s): Kriplani A, Nath J, Takkar D, Maya, Kaul HL. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1998 September; 80(1): 99-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9758269
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Biocompatibility of poly (DL-lactic acid/glycine) copolymers. Author(s): Schakenraad JM, Dijkstra PJ. Source: Clin Mater. 1991; 7(3): 253-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10149137
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Biology of the postsynaptic glycine receptor. Author(s): Vannier C, Triller A. Source: Int Rev Cytol. 1997; 176: 201-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9394920
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Biphasic modulation of the strychnine-sensitive glycine receptor by Zn2+. Author(s): Bloomenthal AB, Goldwater E, Pritchett DB, Harrison NL. Source: Molecular Pharmacology. 1994 December; 46(6): 1156-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7808436
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Blood ammonia concentrations resulting from absorption of irrigating fluid containing glycine and ethanol during transurethral resection of the prostate. Author(s): Hahn RG. Source: Scandinavian Journal of Urology and Nephrology. 1991; 25(2): 115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1871555
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Blood ammonia levels after intravenous infusion of glycine solution with and without ethanol. Author(s): Hahn RG, Sandfeldt L. Source: Scandinavian Journal of Urology and Nephrology. 1999 August; 33(4): 222-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10515083
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Brain glycine levels following lithium toxicity: case report. Author(s): Stanley M, Deutsch SI, Banay-Schwartz M, Peselow ED, Eliazo CE. Source: The Journal of Clinical Psychiatry. 1985 June; 46(6): 239. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3922960
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Brain neurotransmitters in glycine encephalopathy. Author(s): Kish SJ, Dixon LM, Burnham WM, Perry TL, Becker L, Cheng J, Chang LJ, Rebbetoy M. Source: Annals of Neurology. 1988 September; 24(3): 458-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2906530
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Building new function into glycine receptors: a structural model for the activation of the glycine-gated chloride channel. Author(s): Lynch JW, Han NI, Schofield PR. Source: Clinical and Experimental Pharmacology & Physiology. 1999 November; 26(11): 932-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10561818
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Calpain-mediated proteolytic cleavage of the neuronal glycine transporter, GlyT2. Author(s): Baliova M, Betz H, Jursky F. Source: Journal of Neurochemistry. 2004 January; 88(1): 227-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675166
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Cation-selective mutations in the M2 domain of the inhibitory glycine receptor channel reveal determinants of ion-charge selectivity. Author(s): Keramidas A, Moorhouse AJ, Pierce KD, Schofield PR, Barry PH. Source: The Journal of General Physiology. 2002 May; 119(5): 393-410. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981020
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Cellular interactions and degradation of aliphatic poly(ester amide)s derived from glycine and/or 4-amino butyric acid. Author(s): Han SI, Kim BS, Kang SW, Shirai H, Im SS. Source: Biomaterials. 2003 September; 24(20): 3453-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12809774
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Characterization of a first domain of human high glycine-tyrosine and high sulfur keratin-associated protein (KAP) genes on chromosome 21q22.1. Author(s): Rogers MA, Langbein L, Winter H, Ehmann C, Praetzel S, Schweizer J. Source: The Journal of Biological Chemistry. 2002 December 13; 277(50): 48993-9002. Epub 2002 September 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359730
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Characterization of a glycine receptor domain that controls the binding and gating mechanisms of the beta-amino acid agonist, taurine. Author(s): Han NL, Haddrill JL, Lynch JW. Source: Journal of Neurochemistry. 2001 November; 79(3): 636-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11701767
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Characterization of reduced expression of glycine N-methyltransferase in cancerous hepatic tissues using two newly developed monoclonal antibodies. Author(s): Liu HH, Chen KH, Shih YP, Lui WY, Wong FH, Chen YM. Source: Journal of Biomedical Science. 2003 January-February; 10(1): 87-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566990
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Chimeric GABAA/glycine receptors: expression and barbiturate pharmacology. Author(s): Koltchine VV, Ye Q, Finn SE, Harrison NL. Source: Neuropharmacology. 1996; 35(9-10): 1445-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9014160
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Chromosomal localization, structure, single-nucleotide polymorphisms, and expression of the human H-protein gene of the glycine cleavage system (GCSH), a candidate gene for nonketotic hyperglycinemia. Author(s): Kure S, Kojima K, Kudo T, Kanno K, Aoki Y, Suzuki Y, Shinka T, Sakata Y, Narisawa K, Matsubara Y. Source: Journal of Human Genetics. 2001; 46(7): 378-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11450847
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Comparative effects of glycine and D-cycloserine on persistent negative symptoms in schizophrenia: a retrospective analysis. Author(s): Heresco-Levy U, Javitt DC. Source: Schizophrenia Research. 2004 February 1; 66(2-3): 89-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061240
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Comparative surface accessibility of a pore-lining threonine residue (T6') in the glycine and GABA(A) receptors. Author(s): Shan Q, Haddrill JL, Lynch JW. Source: The Journal of Biological Chemistry. 2002 November 22; 277(47): 44845-53. Epub 2002 September 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12239220
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Comparison of taurine- and glycine-induced conformational changes in the M2-M3 domain of the glycine receptor. Author(s): Han NL, Clements JD, Lynch JW. Source: The Journal of Biological Chemistry. 2004 May 7; 279(19): 19559-65. Epub 2004 February 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14981077
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Compound heterozygosity and nonsense mutations in the alpha(1)-subunit of the inhibitory glycine receptor in hyperekplexia. Author(s): Rees MI, Lewis TM, Vafa B, Ferrie C, Corry P, Muntoni F, Jungbluth H, Stephenson JB, Kerr M, Snell RG, Schofield PR, Owen MJ. Source: Human Genetics. 2001 September; 109(3): 267-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702206
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Compound heterozygosity for COL7A1 mutations in twins with dystrophic epidermolysis bullosa: a recessive paternal deletion/insertion mutation and a dominant negative maternal glycine substitution result in a severe phenotype. Author(s): Christiano AM, Anton-Lamprecht I, Amano S, Ebschner U, Burgeson RE, Uitto J. Source: American Journal of Human Genetics. 1996 April; 58(4): 682-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8644730
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Concomitant occasional use of salbutamol influences bronchoprotective responsiveness afforded by formoterol in patients with the glycine-16 genotype. Author(s): Sims EJ, Lipworth BJ. Source: European Journal of Clinical Pharmacology. 2004 January; 59(11): 791-5. Epub 2003 December 11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14668964
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Conserved high affinity ligand binding and membrane association in the native and refolded extracellular domain of the human glycine receptor alpha1-subunit. Author(s): Breitinger U, Breitinger HG, Bauer F, Fahmy K, Glockenhammer D, Becker CM. Source: The Journal of Biological Chemistry. 2004 January 16; 279(3): 1627-36. Epub 2003 October 30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14593111
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Contribution of glycine 146 to a conserved folding module affecting stability and refolding of human glutathione transferase p1-1. Author(s): Kong GK, Polekhina G, McKinstry WJ, Parker MW, Dragani B, Aceto A, Paludi D, Principe DR, Mannervik B, Stenberg G. Source: The Journal of Biological Chemistry. 2003 January 10; 278(2): 1291-302. Epub 2002 October 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12414796
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Contribution of regions distal to glycine-160 to the anticoagulant activity of tissue factor pathway inhibitor. Author(s): Lockett JM, Mast AE. Source: Biochemistry. 2002 April 16; 41(15): 4989-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939795
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Contribution of two conserved glycine residues to fibrillogenesis of the 106-126 prion protein fragment. Evidence that a soluble variant of the 106-126 peptide is neurotoxic. Author(s): Florio T, Paludi D, Villa V, Principe DR, Corsaro A, Millo E, Damonte G, D'Arrigo C, Russo C, Schettini G, Aceto A. Source: Journal of Neurochemistry. 2003 April; 85(1): 62-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12641727
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Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutrition Survey of young people aged 4-18 years, and a comparison with the survey of people aged 65 years and over. Author(s): Bates CJ, Mansoor MA, Gregory J, Pentiev K, Prentice A. Source: The British Journal of Nutrition. 2002 January; 87(1): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11895315
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Degradation signals in ErbB-2 dictate proteasomal processing and immunogenicity and resist protection by cis glycine-alanine repeat. Author(s): Piechocki MP, Pilon SA, Kelly C, Wei WZ. Source: Cellular Immunology. 2001 September 15; 212(2): 138-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748930
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Delineation of the structural determinants of the N-methyl-D-aspartate receptor glycine binding site. Author(s): Sandhu S, Grimwood S, Mortishire-Smith RJ, Whiting PJ, le Bourdelles B. Source: Journal of Neurochemistry. 1999 April; 72(4): 1694-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10098879
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Demonstration of glycine peaks at 3.50 ppm in a patient with van der Knaap syndrome. Author(s): Sener RN. Source: Ajnr. American Journal of Neuroradiology. 2001 September; 22(8): 1587-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11559512
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Desensitization of homomeric alpha1 glycine receptor increases with receptor density. Author(s): Legendre P, Muller E, Badiu CI, Meier J, Vannier C, Triller A. Source: Molecular Pharmacology. 2002 October; 62(4): 817-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12237328
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Destabilization of osteogenesis imperfecta collagen-like model peptides correlates with the identity of the residue replacing glycine. Author(s): Beck K, Chan VC, Shenoy N, Kirkpatrick A, Ramshaw JA, Brodsky B. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 April 11; 97(8): 4273-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10725403
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Determination of the molecular weight distribution of non-enzymatic browning products formed by roasting of glucose and glycine and studies on their effects on NADPH-cytochrome c-reductase and glutathione-S-transferase in Caco-2 cells. Author(s): Hofmann T, Ames J, Krome K, Faist V. Source: Die Nahrung. 2001 June; 45(3): 189-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11455786
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Diagnostic enzyme assay that uses stable-isotope-labeled substrates to detect Larginine:glycine amidinotransferase deficiency. Author(s): Verhoeven NM, Schor DS, Roos B, Battini R, Stockler-Ipsiroglu S, Salomons GS, Jakobs C. Source: Clinical Chemistry. 2003 May; 49(5): 803-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12709373
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Different effects of point mutations within the B-Raf glycine-rich loop in colorectal tumors on mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase and nuclear factor kappaB pathway and cellular transformation. Author(s): Ikenoue T, Hikiba Y, Kanai F, Aragaki J, Tanaka Y, Imamura J, Imamura T, Ohta M, Ijichi H, Tateishi K, Kawakami T, Matsumura M, Kawabe T, Omata M. Source: Cancer Research. 2004 May 15; 64(10): 3428-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15150094
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Differential effects of ethanol on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters. Author(s): Nunez E, Lopez-Corcuera B, Martinez-Maza R, Aragon C. Source: British Journal of Pharmacology. 2000 February; 129(4): 802-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10683205
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Differential effects of the tricyclic antidepressant amoxapine on glycine uptake mediated by the recombinant GLYT1 and GLYT2 glycine transporters. Author(s): Nunez E, Lopez-Corcuera B, Vazquez J, Gimenez C, Aragon C. Source: British Journal of Pharmacology. 2000 January; 129(1): 200-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10694221
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Differential properties of two stably expressed brain-specific glycine transporters. Author(s): Lopez-Corcuera B, Martinez-Maza R, Nunez E, Roux M, Supplisson S, Aragon C. Source: Journal of Neurochemistry. 1998 November; 71(5): 2211-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9798949
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Differentiation of Malassezia furfur and Malassezia sympodialis by glycine utilization. Author(s): Murai T, Nakamura Y, Kano R, Watanabe S, Hasegawa A. Source: Mycoses. 2002 June; 45(5-6): 180-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12100536
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Disease-specific human glycine receptor alpha1 subunit causes hyperekplexia phenotype and impaired glycine- and GABA(A)-receptor transmission in transgenic mice. Author(s): Becker L, von Wegerer J, Schenkel J, Zeilhofer HU, Swandulla D, Weiher H. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 April 1; 22(7): 2505-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923415
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Disrupted growth plates and progressive deformities in osteogenesis imperfecta as a result of the substitution of glycine 585 by valine in the alpha 2 (I) chain of type I collagen. Author(s): Cole WG, Chan D, Chow CW, Rogers JG, Bateman JF. Source: Journal of Medical Genetics. 1996 November; 33(11): 968-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8950681
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Dominant dystrophic epidermolysis bullosa (Pasini) caused by a novel glycine substitution mutation in the type VII collagen gene (COL7A1). Author(s): Jonkman MF, Moreno G, Rouan F, Oranje AP, Pulkkinen L, Uitto J. Source: The Journal of Investigative Dermatology. 1999 May; 112(5): 815-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10233777
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Dose escalation study of the NMDA glycine-site antagonist licostinel in acute ischemic stroke. Author(s): Albers GW, Clark WM, Atkinson RP, Madden K, Data JL, Whitehouse MJ. Source: Stroke; a Journal of Cerebral Circulation. 1999 March; 30(3): 508-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10066844
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Double autoimmunostaining with glycine treatment. Author(s): Hasui K, Takatsuka T, Sakamoto R, Matsushita S, Tsuyama S, Izumo S, Murata F. Source: The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society. 2003 September; 51(9): 1169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923242
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Double-blind randomized study of symptoms associated with absorption of glycine 1.5% or mannitol 3% during transurethral resection of the prostate. Author(s): Hahn RG, Sandfeldt L, Nyman CR. Source: The Journal of Urology. 1998 August; 160(2): 397-401. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9679886
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Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity. Author(s): Feng G, Tintrup H, Kirsch J, Nichol MC, Kuhse J, Betz H, Sanes JR. Source: Science. 1998 November 13; 282(5392): 1321-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9812897
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Early oncogene mRNA expression in HT-29 cells treated with the endogenous colon mitosis inhibitor pyroglutamyl-histidyl-glycine. Author(s): Reichelt WH, Liu Y, Luna L, Eigjo K, Reichelt KL. Source: Anticancer Res. 2002 March-April; 22(2A): 991-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12014683
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Effect of enteral glutamine or glycine on whole-body nitrogen kinetics in very-lowbirth-weight infants. Author(s): Parimi PS, Devapatla S, Gruca LL, Amini SB, Hanson RW, Kalhan SC. Source: The American Journal of Clinical Nutrition. 2004 March; 79(3): 402-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985214
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Effect of glycine substitutions on alpha5(IV) chain structure and structure-phenotype correlations in Alport syndrome. Author(s): Wang YF, Ding J, Wang F, Bu DF. Source: Biochemical and Biophysical Research Communications. 2004 April 16; 316(4): 1143-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15044104
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Effect of naturally occurring mutations in human glycine N-methyltransferase on activity and conformation. Author(s): Luka Z, Wagner C. Source: Biochemical and Biophysical Research Communications. 2003 December 26; 312(4): 1067-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651980
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Effect of single and combined supply of glutamine, glycine, N-acetylcysteine, and R,S-alpha-lipoic acid on glutathione content of myelomonocytic cells. Author(s): Wessner B, Strasser EM, Spittler A, Roth E. Source: Clinical Nutrition (Edinburgh, Lothian). 2003 December; 22(6): 515-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14613752
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Effect of the novel high-affinity glycine-site N-methyl-D-aspartate antagonist ACEA1021 on 125I-MK-801 binding after subdural hematoma in the rat: an in vivo autoradiographic study. Author(s): Di X, Bullock R. Source: Journal of Neurosurgery. 1996 October; 85(4): 655-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8814170
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Effectiveness of zinc gluconate glycine lozenges (Cold-Eeze) against the common cold in school-aged subjects: a retrospective chart review. Author(s): McElroy BH, Miller SP. Source: American Journal of Therapeutics. 2002 November-December; 9(6): 472-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12424502
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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609312
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Electrophysiological characterisation of the antagonist properties of two novel NMDA receptor glycine site antagonists, L-695,902 and L-701,324. Author(s): Priestley T, Laughton P, Macaulay AJ, Hill RG, Kemp JA. Source: Neuropharmacology. 1996; 35(11): 1573-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9025105
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Endogenous glycine and tyrosine production is maintained in adults consuming a marginal-protein diet. Author(s): Gibson NR, Jahoor F, Ware L, Jackson AA. Source: The American Journal of Clinical Nutrition. 2002 March; 75(3): 511-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11864857
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Enhancement of dehydroepiandrosterone solubility and bioavailability by ternary complexation with alpha-cyclodextrin and glycine. Author(s): Mora PC, Cirri M, Allolio B, Carli F, Mura P. Source: Journal of Pharmaceutical Sciences. 2003 November; 92(11): 2177-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603503
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Epstein-Barr virus nuclear antigen 2 binds via its methylated arginine-glycine repeat to the survival motor neuron protein. Author(s): Barth S, Liss M, Voss MD, Dobner T, Fischer U, Meister G, Grasser FA. Source: Journal of Virology. 2003 April; 77(8): 5008-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663808
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Ethanol potentiation of glycine receptors expressed in Xenopus oocytes antagonized by increased atmospheric pressure. Author(s): Davies DL, Trudell JR, Mihic SJ, Crawford DK, Alkana RL. Source: Alcoholism, Clinical and Experimental Research. 2003 May; 27(5): 743-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766618
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Ethanol-glycine irrigating fluid for transurethral resection of the prostate in practice. Author(s): Sharma D. Source: Bju International. 2001 November; 88(7): 804. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11890259
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Experience with ferrous bis-glycine chelate as an iron fortificant in milk. Author(s): Osman AK, al-Othaimeen A. Source: Int J Vitam Nutr Res. 2002 July; 72(4): 257-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12214563
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Expression and purification of glycine N-methyltransferases in Escherichia coli. Author(s): Luka Z, Wagner C. Source: Protein Expression and Purification. 2003 April; 28(2): 280-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12699692
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Expression of glycine receptors in rat sensory neurons vs. HEK293 cells yields different functional properties. Author(s): Kung AY, Rick C, O'Shea S, Harrison NL, McGehee DS. Source: Neuroscience Letters. 2001 August 31; 309(3): 202-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11514076
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Extended experience with glycine for prevention of reperfusion injury after human liver transplantation. Author(s): Schemmer P, Golling M, Kraus T, Mehrabi A, Mayatepek E, Herfarth Ch, Klar E. Source: Transplantation Proceedings. 2002 September; 34(6): 2307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12270410
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Facile solid-phase synthesis of sulfated tyrosine-containing peptides: Part II. Total synthesis of human big gastrin-II and its C-terminal glycine-extended peptide (G34Gly sulfate) by the solid-phase segment condensation approach. Author(s): Kitagawa K, Aida C, Fujiwara H, Yagami T, Futaki S. Source: Chemical & Pharmaceutical Bulletin. 2001 August; 49(8): 958-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11515585
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Facilitation of cell adhesion by immobilized dengue viral nonstructural protein 1 (NS1): arginine-glycine-aspartic acid structural mimicry within the dengue viral NS1 antigen. Author(s): Chang HH, Shyu HF, Wang YM, Sun DS, Shyu RH, Tang SS, Huang YS. Source: The Journal of Infectious Diseases. 2002 September 15; 186(6): 743-51. Epub 2002 August 28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198607
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Factor XSt. Louis II. Identification of a glycine substitution at residue 7 and characterization of the recombinant protein. Author(s): Rudolph AE, Mullane MP, Porche-Sorbet R, Tsuda S, Miletich JP. Source: The Journal of Biological Chemistry. 1996 November 8; 271(45): 28601-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8910490
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Failure of N-2-mercaptopropionyl glycine to reduce myocardial infarction after 3 days of reperfusion in rabbits. Author(s): Miki T, Cohen MV, Downey JM. Source: Basic Research in Cardiology. 1999 June; 94(3): 180-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10424236
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Familial Alzheimer's disease. A pedigree with a mis-sense mutation in the amyloid precursor protein gene (amyloid precursor protein 717 valine-->glycine). Author(s): Kennedy AM, Newman S, McCaddon A, Ball J, Roques P, Mullan M, Hardy J, Chartier-Harlin MC, Frackowiak RS, Warrington EK, et al. Source: Brain; a Journal of Neurology. 1993 April; 116 ( Pt 2): 309-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8461968
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Fast potentiation of glycine receptor channels of intracellular calcium in neurons and transfected cells. Author(s): Fucile S, De Saint Jan D, de Carvalho LP, Bregestovski P. Source: Neuron. 2000 November; 28(2): 571-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11144365
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First-trimester prenatal diagnosis of non-ketotic hyperglycinaemia by a micro assay of glycine cleavage enzyme. Author(s): Rolland MO, Mandon G, Mathieu M. Source: Prenatal Diagnosis. 1993 August; 13(8): 771-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8284296
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Flexible glycine rich motif of Escherichia coli deoxyuridine triphosphate nucleotidohydrolase is important for functional but not for structural integrity of the enzyme. Author(s): Vertessy BG. Source: Proteins. 1997 August; 28(4): 568-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9261872
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Flow cytometric measurement of kinetic and equilibrium binding parameters of arginine-glycine-aspartic acid ligands in binding to glycoprotein IIb/IIIa on platelets. Author(s): Bednar B, Cunningham ME, McQueney PA, Egbertson MS, Askew BC, Bednar RA, Hartman GD, Gould RJ. Source: Cytometry : the Journal of the Society for Analytical Cytology. 1997 May 1; 28(1): 58-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9136756
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Forget About "van der Knaap syndrome," forget about glycine. Author(s): Van der Knaap MS. Source: Ajnr. American Journal of Neuroradiology. 2003 May; 24(5): 1030; Author Reply 1030. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748116
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Formation of glycine receptor clusters and their accumulation at synapses. Author(s): Meier J, Meunier-Durmort C, Forest C, Triller A, Vannier C. Source: Journal of Cell Science. 2000 August; 113 ( Pt 15): 2783-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10893193
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Four new cases of lethal osteogenesis imperfecta due to glycine substitutions in COL1A1 and genes. Mutations in brief no. 152. Online. Author(s): Mottes M, Gomez Lira M, Zolezzi F, Valli M, Lisi V, Freising P. Source: Human Mutation. 1998; 12(1): 71-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10627137
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Free lysine, glycine, alanine, glutamic acid and aspartic acid reduce the glycation of human lens proteins by galactose. Author(s): Ramakrishnan S, Sulochana KN, Punitham R. Source: Indian J Biochem Biophys. 1997 December; 34(6): 518-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9594433
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Function and structure in glycine receptors and some of their relatives. Author(s): Colquhoun D, Sivilotti LG. Source: Trends in Neurosciences. 2004 June; 27(6): 337-44. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15165738
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Functional antagonism with formoterol and salmeterol in asthmatic patients expressing the homozygous glycine-16 beta(2)-adrenoceptor polymorphism. Author(s): Lipworth BJ, Dempsey OJ, Aziz I. Source: Chest. 2000 August; 118(2): 321-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936119
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Functional characterisation of the human alpha1 glycine receptor in a fluorescencebased membrane potential assay. Author(s): Jensen AA, Kristiansen U. Source: Biochemical Pharmacology. 2004 May 1; 67(9): 1789-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081878
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Functional expression and purification of a homomeric human alpha 1 glycine receptor in baculovirus-infected insect cells. Author(s): Cascio M, Schoppa NE, Grodzicki RL, Sigworth FJ, Fox RO. Source: The Journal of Biological Chemistry. 1993 October 15; 268(29): 22135-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8408073
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Functional reconstitution and characterization of recombinant human alpha 1-glycine receptors. Author(s): Cascio M, Shenkel S, Grodzicki RL, Sigworth FJ, Fox RO. Source: The Journal of Biological Chemistry. 2001 June 15; 276(24): 20981-8. Epub 2001 January 05. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11145968
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Functional significance of conserved glycine 127 in a human dual-specificity protein tyrosine phosphatase. Author(s): Zeng WY, Wang YH, Zhang YC, Yang WL, Shi YY. Source: Biochemistry. Biokhimiia. 2003 June; 68(6): 634-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943507
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Gastrimmune raises antibodies that neutralize amidated and glycine-extended gastrin-17 and inhibit the growth of colon cancer. Author(s): Watson SA, Michaeli D, Grimes S, Morris TM, Robinson G, Varro A, Justin TA, Hardcastle JD. Source: Cancer Research. 1996 February 15; 56(4): 880-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8631028
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Gene structure and alternative splicing of the mouse glycine transporter type-2. Author(s): Ebihara S, Yamamoto T, Obata K, Yanagawa Y. Source: Biochemical and Biophysical Research Communications. 2004 May 7; 317(3): 857-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081419
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Gene Symbol: GLDC. Disease: NKH glycine encephalopathy. Author(s): Toone JR, Applegarth DA, Laliberte G. Source: Human Genetics. 2003 October; 113(5): 465. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14552331
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Genetic basis of Bart's syndrome: a glycine substitution mutation in type VII collagen gene. Author(s): Christiano AM, Bart BJ, Epstein EH Jr, Uitto J. Source: The Journal of Investigative Dermatology. 1996 April; 106(4): 778-80. Corrected and Republished In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8618021
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Glycine 154 of the equilibrative nucleoside transporter, hENT1, is important for nucleoside transport and for conferring sensitivity to the inhibitors nitrobenzylthioinosine, dipyridamole, and dilazep. Author(s): SenGupta DJ, Unadkat JD. Source: Biochemical Pharmacology. 2004 February 1; 67(3): 453-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15037197
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Glycine absorption and hypocalcaemia. Author(s): Hahn RG. Source: British Journal of Anaesthesia. 1996 December; 77(6): 810-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9014646
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Glycine activation of human homomeric alpha 1 glycine receptors is sensitive to pressure in the range of the high pressure nervous syndrome. Author(s): Roberts RJ, Shelton CJ, Daniels S, Smith EB. Source: Neuroscience Letters. 1996 April 19; 208(2): 125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8859906
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Glycine irrigant absorption syndrome following cystoscopy. Author(s): Siddiqui MA, Berns JS, Baime MJ. Source: Clinical Nephrology. 1996 May; 45(5): 365-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8738677
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Glycine N-methyltransferase tumor susceptibility gene in the benzo(a)pyrenedetoxification pathway. Author(s): Chen SY, Lin JR, Darbha R, Lin P, Liu TY, Chen YM. Source: Cancer Research. 2004 May 15; 64(10): 3617-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15150120
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Glycine substitutions in the triple-helical region of type VII collagen result in a spectrum of dystrophic epidermolysis bullosa phenotypes and patterns of inheritance. Author(s): Christiano AM, McGrath JA, Tan KC, Uitto J. Source: American Journal of Human Genetics. 1996 April; 58(4): 671-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8644729
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Glycine therapy of schizophrenia. Author(s): Javitt DC. Source: Biological Psychiatry. 1996 October 1; 40(7): 684-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8886307
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Glycine therapy of schizophrenia: some caveats. Author(s): Waziri R. Source: Biological Psychiatry. 1996 February 1; 39(3): 155-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8837976
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Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to antipsychotics for the treatment of schizophrenia. Author(s): Tsai G, Lane HY, Yang P, Chong MY, Lange N. Source: Biological Psychiatry. 2004 March 1; 55(5): 452-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023571
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Glycine transporters not only take out the garbage, they recycle. Author(s): Brasnjo G, Otis TS. Source: Neuron. 2003 November 13; 40(4): 667-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622571
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Glycine: the other inhibitory neurotransmitter. Author(s): Schofield P. Source: Alcoholism, Clinical and Experimental Research. 1996 November; 20(8 Suppl): 219A-223A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8947269
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Glycine--an inert amino acid comes alive. Author(s): Roth E, Zellner M, Wessner B, Strasser E, Manhart N, Oehler R, Spittler A. Source: Nutrition (Burbank, Los Angeles County, Calif.). 2003 September; 19(9): 817-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12921899
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Glycine-arginine-alpha-ketoisocaproic acid improves performance of repeated cycling sprints. Author(s): Buford BN, Koch AJ. Source: Medicine and Science in Sports and Exercise. 2004 April; 36(4): 583-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15064584
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Glycine-extended gastrin induces matrix metalloproteinase-1- and -3-mediated invasion of human colon cancer cells through type I collagen gel and Matrigel. Author(s): Baba M, Itoh K, Tatsuta M. Source: International Journal of Cancer. Journal International Du Cancer. 2004 August 10; 111(1): 23-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15185339
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Glycine-extended gastrin promotes the growth of lung cancer. Author(s): Koh TJ, Field JK, Varro A, Liloglou T, Fielding P, Cui G, Houghton J, Dockray GJ, Wang TC. Source: Cancer Research. 2004 January 1; 64(1): 196-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14729624
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Hemizygosity for a glycine substitution in collagen XVII: unfolding and degradation of the ectodomain. Author(s): Tasanen K, Floeth M, Schumann H, Bruckner-Tuderman L. Source: The Journal of Investigative Dermatology. 2000 August; 115(2): 207-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10951237
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Hemophilia B with mutations at glycine-48 of factor IX exhibited delayed activation by the factor VIIa-tissue factor complex. Author(s): Wu PC, Hamaguchi N, Yu YS, Shen MC, Lin SW. Source: Thrombosis and Haemostasis. 2000 October; 84(4): 626-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11057861
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Hepatic taurine, glycine and individual bile acids in early human fetus. Author(s): Itoh S, Onishi S. Source: Early Human Development. 2000 January; 57(1): 71-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10690713
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Heritable mutations in the glycine, GABAA, and nicotinic acetylcholine receptors provide new insights into the ligand-gated ion channel receptor superfamily. Author(s): Vafa B, Schofield PR. Source: Int Rev Neurobiol. 1998; 42: 285-332. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9476176
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Heterozygous glycine substitution in the COL11A2 gene in the original patient with the Weissenbacher-Zweymuller syndrome demonstrates its identity with heterozygous OSMED (nonocular Stickler syndrome). Author(s): Pihlajamaa T, Prockop DJ, Faber J, Winterpacht A, Zabel B, Giedion A, Wiesbauer P, Spranger J, Ala-Kokko L. Source: American Journal of Medical Genetics. 1998 November 2; 80(2): 115-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9805126
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High-dose glycine added to olanzapine and risperidone for the treatment of schizophrenia. Author(s): Heresco-Levy U, Ermilov M, Lichtenberg P, Bar G, Javitt DC. Source: Biological Psychiatry. 2004 January 15; 55(2): 165-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732596
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Homo-oligomerization of human corneodesmosin is mediated by its N-terminal glycine loop domain. Author(s): Caubet C, Jonca N, Lopez F, Esteve JP, Simon M, Serre G. Source: The Journal of Investigative Dermatology. 2004 March; 122(3): 747-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086562
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Human glycine decarboxylase gene (GLDC) and its highly conserved processed pseudogene (psiGLDC): their structure and expression, and the identification of a large deletion in a family with nonketotic hyperglycinemia. Author(s): Takayanagi M, Kure S, Sakata Y, Kurihara Y, Ohya Y, Kajita M, Tada K, Matsubara Y, Narisawa K. Source: Human Genetics. 2000 March; 106(3): 298-305. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10798358
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Human glycine N-methyltransferase is unfolded by urea through a compact monomer state. Author(s): Luka Z, Wagner C. Source: Archives of Biochemistry and Biophysics. 2003 December 1; 420(1): 153-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14622985
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Human hepatic metabolism of a novel 2-carboxyindole glycine antagonist for stroke: in vitro-in vivo correlations. Author(s): Gilissen RA, Ferrari L, Barnaby RJ, Kajbaf M. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 2000 September; 30(9): 843-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11055263
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Human immunodeficiency virus type-1 integrase containing a glycine to serine mutation at position 140 is attenuated for catalysis and resistant to integrase inhibitors. Author(s): King PJ, Lee DJ, Reinke RA, Victoria JG, Beale K, Robinson WE Jr. Source: Virology. 2003 February 1; 306(1): 147-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12620807
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Human variability for metabolic pathways with limited data (CYP2A6, CYP2C9, CYP2E1, ADH, esterases, glycine and sulphate conjugation). Author(s): Dorne JL, Walton K, Renwick AG. Source: Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association. 2004 March; 42(3): 397-421. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14871582
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Hydrolysis of glycine-containing elastin pentapeptides by LasA, a metalloelastase from Pseudomonas aeruginosa. Author(s): Vessillier S, Delolme F, Bernillon J, Saulnier J, Wallach J. Source: European Journal of Biochemistry / Febs. 2001 February; 268(4): 1049-57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11179971
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Hydrophobic interactions mediate binding of the glycine receptor beta-subunit to gephyrin. Author(s): Kneussel M, Hermann A, Kirsch J, Betz H. Source: Journal of Neurochemistry. 1999 March; 72(3): 1323-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10037506
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Hydroxylated residues influence desensitization behaviour of recombinant alpha3 glycine receptor channels. Author(s): Breitinger HG, Villmann C, Rennert J, Ballhausen D, Becker CM. Source: Journal of Neurochemistry. 2002 October; 83(1): 30-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358726
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Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB). Author(s): Rees MI, Lewis TM, Kwok JB, Mortier GR, Govaert P, Snell RG, Schofield PR, Owen MJ. Source: Human Molecular Genetics. 2002 April 1; 11(7): 853-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11929858
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Hyperekplexia mutation of glycine receptors: decreased gating efficacy with altered binding thermodynamics. Author(s): Maksay G, Biro T, Laube B. Source: Biochemical Pharmacology. 2002 July 15; 64(2): 285-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12123749
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Hypochlorous acid generated by myeloperoxidase modifies adjacent tryptophan and glycine residues in the catalytic domain of matrix metalloproteinase-7 (matrilysin): an oxidative mechanism for restraining proteolytic activity during inflammation. Author(s): Fu X, Kassim SY, Parks WC, Heinecke JW. Source: The Journal of Biological Chemistry. 2003 August 1; 278(31): 28403-9. Epub 2003 May 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12759346
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Hypothesis: glucagon receptor glycine to serine missense mutation contributes to one in 20 cases of essential hypertension. Author(s): Morris BJ, Chambers SM. Source: Clinical and Experimental Pharmacology & Physiology. 1996 December; 23(12): 1035-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8977155
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Identification of a novel residue within the second transmembrane domain that confers use-facilitated block by picrotoxin in glycine alpha 1 receptors. Author(s): Dibas MI, Gonzales EB, Das P, Bell-Horner CL, Dillon GH. Source: The Journal of Biological Chemistry. 2002 March 15; 277(11): 9112-7. Epub 2001 December 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744711
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Identification of the first reported splice site mutation (IVS7-1G-->A) in the aminomethyltransferase (T-protein) gene (AMT) of the glycine cleavage complex in 3 unrelated families with nonketotic hyperglycinemia. Author(s): Toone JR, Applegarth DA, Coulter-Mackie MB, James ER. Source: Human Mutation. 2001; 17(1): 76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11139253
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Identification of two cyclooxygenase active site residues, Leucine 384 and Glycine 526, that control carbon ring cyclization in prostaglandin biosynthesis. Author(s): Schneider C, Boeglin WE, Brash AR. Source: The Journal of Biological Chemistry. 2004 February 6; 279(6): 4404-14. Epub 2003 October 31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14594816
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Improving endothelial cell retention for single stage seeding of prosthetic grafts: use of polymer sequences of arginine-glycine-aspartate. Author(s): Tiwari A, Kidane A, Salacinski H, Punshon G, Hamilton G, Seifalian AM. Source: European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery. 2003 April; 25(4): 325-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12651170
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In vitro interaction of the glycine receptor with the leptin receptor. Author(s): Leite JF, Gribble B, Randolph N, Cascio M. Source: Physiology & Behavior. 2002 December; 77(4-5): 565-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12527000
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In vivo 1H magnetic resonance spectroscopic measurement of brain glycine levels in nonketotic hyperglycinemia. Author(s): Gabis L, Parton P, Roche P, Lenn N, Tudorica A, Huang W. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2001 April; 11(2): 209-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11296595
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Inhibition of alpha-subunit glycine receptors by quinoxalines. Author(s): Meier J, Schmieden V. Source: Neuroreport. 2003 August 6; 14(11): 1507-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960774
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Inhibition of puerperal lactation with 2-mercaptopropionyl-glycine. Author(s): Akrivis C, Vezyraki P, Kiortsis DN, Fotopoulos A, Evangelou A. Source: European Journal of Clinical Pharmacology. 2000 December; 56(9-10): 621-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11214766
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Insights into the structural basis for zinc inhibition of the glycine receptor. Author(s): Nevin ST, Cromer BA, Haddrill JL, Morton CJ, Parker MW, Lynch JW. Source: The Journal of Biological Chemistry. 2003 August 1; 278(31): 28985-92. Epub 2003 May 09. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12740384
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Interaction of the neuroprotective drug riluzole with GABA(A) and glycine receptor channels. Author(s): Mohammadi B, Krampfl K, Moschref H, Dengler R, Bufler J. Source: European Journal of Pharmacology. 2001 Mar16; 415(2-3): 135-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11274991
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Intravascular absorption of glycine irrigating solution during shoulder arthroscopy: a case report and follow-up study. Author(s): Ichai C, Ciais JF, Roussel LJ, Levraut J, Candito M, Boileau P, Grimaud D. Source: Anesthesiology. 1996 December; 85(6): 1481-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8968197
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Iron bis-glycine chelate competes for the nonheme-iron absorption pathway. Author(s): Pineda O. Source: The American Journal of Clinical Nutrition. 2003 September; 78(3): 495-6; Author Reply 496. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12936936
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Iron bis-glycine chelate competes for the nonheme-iron absorption pathway. Author(s): Pizarro F, Olivares M, Hertrampf E, Mazariegos DI, Arredondo M, Letelier A, Gidi V. Source: The American Journal of Clinical Nutrition. 2002 September; 76(3): 577-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198002
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Is the ability of urinary tract pathogens to accumulate glycine betaine a factor in the virulence of pathogenic strains? Author(s): Peddie BA, Chambers ST, Lever M. Source: The Journal of Laboratory and Clinical Medicine. 1996 October; 128(4): 417-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8833891
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Isoform heterogeneity of the human gephyrin gene (GPHN), binding domains to the glycine receptor, and mutation analysis in hyperekplexia. Author(s): Rees MI, Harvey K, Ward H, White JH, Evans L, Duguid IC, Hsu CC, Coleman SL, Miller J, Baer K, Waldvogel HJ, Gibbon F, Smart TG, Owen MJ, Harvey RJ, Snell RG. Source: The Journal of Biological Chemistry. 2003 July 4; 278(27): 24688-96. Epub 2003 April 08. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12684523
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Jejunal absorption rates of glucose and glycine in post-infective tropical malabsorption. Author(s): Cook GC. Source: Transactions of the Royal Society of Tropical Medicine and Hygiene. 1981; 75(3): 378-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7324105
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Jejunal absorption rates of glucose, glycine and glycylglycine in Zambian African adults with malnutrition. Author(s): Cook GC. Source: The British Journal of Nutrition. 1974 November; 32(3): 503-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4139969
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JMV1155: a novel inhibitor of glycine-extended progastrin-mediated growth of a human colon cancer in vivo. Author(s): Litvak DA, Hellmich MR, Iwase K, Evers BM, Martinez J, Amblard M, Townsend CM Jr. Source: Anticancer Res. 1999 January-February; 19(1A): 45-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10226523
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Kinetic analysis of recombinant mammalian alpha(1) and alpha(1)beta glycine receptor channels. Author(s): Mohammadi B, Krampfl K, Cetinkaya C, Moschref H, Grosskreutz J, Dengler R, Bufler J. Source: European Biophysics Journal : Ebj. 2003 September; 32(6): 529-36. Epub 2003 February 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551753
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Kinetic and mutational analysis of Zn2+ modulation of recombinant human inhibitory glycine receptors. Author(s): Laube B, Kuhse J, Betz H. Source: The Journal of Physiology. 2000 January 15; 522 Pt 2: 215-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10639099
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Kinetic determinants of agonist action at the recombinant human glycine receptor. Author(s): Lewis TM, Schofield PR, McClellan AM. Source: The Journal of Physiology. 2003 June 1; 549(Pt 2): 361-74. Epub 2003 April 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679369
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Kinetics of a glycine for Arg-47 human alcohol dehydrogenase mutant can be explained by Lys-228 recruitment into the pyrophosphate binding site. Author(s): Stone CL, Hurley TD, Amzel LM, Dunn MF, Bosron WF. Source: Advances in Experimental Medicine and Biology. 1993; 328: 429-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8388156
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Kinetics of competitive inhibition of salicylic acid conjugation with glycine in man. Author(s): Levy G, Amsel LP. Source: Biochemical Pharmacology. 1966 August; 15(8): 1033-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5973152
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Kinked collagen VI tetramers and reduced microfibril formation as a result of Bethlem myopathy and introduced triple helical glycine mutations. Author(s): Lamande SR, Morgelin M, Selan C, Jobsis GJ, Baas F, Bateman JF. Source: The Journal of Biological Chemistry. 2002 January 18; 277(3): 1949-56. Epub 2001 November 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11707460
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Kupffer cell-dependent reperfusion injury in liver transplantation: new clinically relevant use of glycine. Author(s): Thurman RG, Schemmer P, Zhong Z, Bunzendahl H, von Frankenberg M, Lemasters JJ. Source: Langenbecks Arch Chir Suppl Kongressbd. 1998; 115: 185-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9931608
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Lack of influence of glycine on the single dose pharmacokinetics of acetylsalicylic acid in man. Author(s): Schurer M, Bias-Imhoff U, Schulz HU, Schwantes U, Riechers AM. Source: Int J Clin Pharmacol Ther. 1996 July; 34(7): 282-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8832303
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Lack of sugar discrimination by human Pol mu requires a single glycine residue. Author(s): Ruiz JF, Juarez R, Garcia-Diaz M, Terrados G, Picher AJ, Gonzalez-Barrera S, Fernandez de Henestrosa AR, Blanco L. Source: Nucleic Acids Research. 2003 August 1; 31(15): 4441-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12888504
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L-cysteine, glycine and dl-threonine in the treatment of hypostatic leg ulceration: a placebo-controlled study. Author(s): Harvey SG, Gibson JR, Burke CA. Source: Pharmatherapeutica. 1985; 4(4): 227-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3933019
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L-Glycine: a novel antiinflammatory, immunomodulatory, and cytoprotective agent. Author(s): Zhong Z, Wheeler MD, Li X, Froh M, Schemmer P, Yin M, Bunzendaul H, Bradford B, Lemasters JJ. Source: Current Opinion in Clinical Nutrition and Metabolic Care. 2003 March; 6(2): 22940. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12589194
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LIM-domain protein cysteine- and glycine-rich protein 2 (CRP2) is a novel marker of hepatic stellate cells and binding partner of the protein inhibitor of activated STAT1. Author(s): Weiskirchen R, Moser M, Weiskirchen S, Erdel M, Dahmen S, Buettner R, Gressner AM. Source: The Biochemical Journal. 2001 November 1; 359(Pt 3): 485-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11672422
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Liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric analysis of glycine conjugates and urinary isovalerylglycine in isovaleric acidemia. Author(s): Ito T, Kidouchi K, Sugiyama N, Kajita M, Chiba T, Niwa T, Wada Y. Source: Journal of Chromatography. B, Biomedical Applications. 1995 August 18; 670(2): 317-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8548022
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Localization of the glycine receptor alpha 1 subunit gene (GLRA1) to chromosome 5q32 by FISH. Author(s): Baker E, Sutherland GR, Schofield PR. Source: Genomics. 1994 July 15; 22(2): 491-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7806244
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Localization of thrombospondin and its cysteine-serine-valine-threonine-cysteineglycine-specific receptor in human breast carcinoma. Author(s): Tuszynski GP, Nicosia RF. Source: Laboratory Investigation; a Journal of Technical Methods and Pathology. 1994 February; 70(2): 228-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7511188
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Localization of thrombospondin-1 and its cysteine-serine-valine-threonine-cysteineglycine receptor in colonic anastomotic healing tissue. Author(s): Roth JJ, Buckmire MA, Rolandelli RH, Granick MS, Tuszynski GP. Source: Histology and Histopathology. 1998 October; 13(4): 967-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9810490
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L-Serine and glycine based ceramide analogues as transdermal permeation enhancers: polar head size and hydrogen bonding. Author(s): Vavrova K, Hrabalek A, Dolezal P, Holas T, Zbytovska J. Source: Bioorganic & Medicinal Chemistry Letters. 2003 July 21; 13(14): 2351-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12824032
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Metal-dependent alpha-helix formation promoted by the glycine-rich octapeptide region of prion protein. Author(s): Miura T, Hori-i A, Takeuchi H. Source: Febs Letters. 1996 November 4; 396(2-3): 248-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8914996
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MHC allele-specific binding of a malaria peptide makes it become promiscuous on fitting a glycine residue into pocket 6. Author(s): Vargas LE, Parra CA, Salazar LM, Guzman F, Pinto M, Patarroyo ME. Source: Biochemical and Biophysical Research Communications. 2003 July 18; 307(1): 148-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849994
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Modulation of glycine-activated ion channel function by G-protein betagamma subunits. Author(s): Yevenes GE, Peoples RW, Tapia JC, Parodi J, Soto X, Olate J, Aguayo LG. Source: Nature Neuroscience. 2003 August; 6(8): 819-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858180
96
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Molecular and genetic insights into ligand binding and signal transduction at the inhibitory glycine receptor. Author(s): Schofield PR, Lynch JW, Rajendra S, Pierce KD, Handford CA, Barry PH. Source: Cold Spring Harb Symp Quant Biol. 1996; 61: 333-42. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9246463
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Molecular determinants of proton modulation of glycine receptors. Author(s): Chen Z, Dillon GH, Huang R. Source: The Journal of Biological Chemistry. 2004 January 9; 279(2): 876-83. Epub 2003 October 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563849
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Molecular genetic and potential biochemical characteristics of patients with T-protein deficiency as a cause of glycine encephalopathy (NKH). Author(s): Toone JR, Applegarth DA, Levy HL, Coulter-Mackie MB, Lee G. Source: Molecular Genetics and Metabolism. 2003 August; 79(4): 272-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948742
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Multiple sites of ethanol action in alpha1 and alpha2 glycine receptors suggested by sensitivity to pressure antagonism. Author(s): Davies DL, Crawford DK, Trudell JR, Mihic SJ, Alkana RL. Source: Journal of Neurochemistry. 2004 June; 89(5): 1175-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15147510
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Mutagenic activity of glycine upon nitrosation in the presence of chloride and human gastric juice: a possible role in gastric carcinogenesis. Author(s): Gaspar J, Laires A, Va S, Pereira S, Mariano A, Quina M, Rueff J. Source: Teratogenesis, Carcinogenesis, and Mutagenesis. 1996; 16(5): 275-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9122893
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Mutational analysis of the fusion peptide of the human immunodeficiency virus type 1: identification of critical glycine residues. Author(s): J Invest Dermatol. 1996 Jun;106(6):1340-2 Source: Virology. 1996 April 1; 218(1): 94-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8752681
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Mycosporine glycine protects biological systems against photodynamic damage by quenching singlet oxygen with a high efficiency. Author(s): Suh HJ, Lee HW, Jung J. Source: Photochemistry and Photobiology. 2003 August; 78(2): 109-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12945577
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Natriuresis and "dilutional" hyponatremia after infusion of glycine 1.5%. Author(s): Hahn RG. Source: Journal of Clinical Anesthesia. 2001 May; 13(3): 167-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11377153
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Need rods? Get glycine receptors and taurine. Author(s): Renteria RC, Johnson J, Copenhagen DR. Source: Neuron. 2004 March 25; 41(6): 839-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046714
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Neuronal cell lines expressing PC5, but not PC1 or PC2, process Pro-CCK into glycine-extended CCK 12 and 22. Author(s): Cain BM, Vishnuvardhan D, Beinfeld MC. Source: Peptides. 2001 August; 22(8): 1271-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11457520
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NMDA receptor antagonists and glycine site NMDA antagonists. Author(s): Madden K. Source: Current Medical Research and Opinion. 2002; 18 Suppl 2: S27-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12365826
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NMR conformational analysis of cis and trans proline isomers in the neutrophil chemoattractant, N-acetyl-proline-glycine-proline. Author(s): Lee YC, Jackson PL, Jablonsky MJ, Muccio DD, Pfister RR, Haddox JL, Sommers CI, Anantharamaiah GM, Chaddha M. Source: Biopolymers. 2001 May; 58(6): 548-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11246204
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NMR structure and backbone dynamics of the extended second transmembrane domain of the human neuronal glycine receptor alpha1 subunit. Author(s): Yushmanov VE, Mandal PK, Liu Z, Tang P, Xu Y. Source: Biochemistry. 2003 April 8; 42(13): 3989-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667090
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NMR structures of the second transmembrane domain of the human glycine receptor alpha(1) subunit: model of pore architecture and channel gating. Author(s): Tang P, Mandal PK, Xu Y. Source: Biophysical Journal. 2002 July; 83(1): 252-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12080117
98
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No cross-resistance or selection of HIV-1 resistant mutants in vitro to the antiretroviral tripeptide glycyl-prolyl-glycine-amide. Author(s): Andersson E, Horal P, Vahlne A, Svennerholm B. Source: Antiviral Research. 2004 February; 61(2): 119-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14670585
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Nonketotic hyperglycinemia (glycine encephalopathy): laboratory diagnosis. Author(s): Applegarth DA, Toone JR. Source: Molecular Genetics and Metabolism. 2001 September-October; 74(1-2): 139-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592811
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Novel mutations in the P-protein (glycine decarboxylase) gene in patients with glycine encephalopathy (non-ketotic hyperglycinemia). Author(s): Toone JR, Applegarth DA, Kure S, Coulter-Mackie MB, Sazegar P, Kojima K, Ichinohe A. Source: Molecular Genetics and Metabolism. 2002 July; 76(3): 243-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12126939
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Oligodendroglial gliomatosis cerebri: (1)H-MRS suggests elevated glycine/inositol levels. Author(s): Gutowski NJ, Gomez-Anson B, Torpey N, Revesz T, Miller D, Rudge P. Source: Neuroradiology. 1999 September; 41(9): 650-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10525765
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Openings of the rat recombinant alpha 1 homomeric glycine receptor as a function of the number of agonist molecules bound. Author(s): Beato M, Groot-Kormelink PJ, Colquhoun D, Sivilotti LG. Source: The Journal of General Physiology. 2002 May; 119(5): 443-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981023
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Opposing effects of molecular volume and charge at the hyperekplexia site alpha 1(P250) govern glycine receptor activation and desensitization. Author(s): Breitinger HG, Villmann C, Becker K, Becker CM. Source: The Journal of Biological Chemistry. 2001 August 10; 276(32): 29657-63. Epub 2001 June 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11395484
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Osmoprotective effect of glycine betaine on foreign protein production in hyperosmotic recombinant chinese hamster ovary cell cultures differs among cell lines. Author(s): Ryu JS, Kim TK, Chung JY, Lee GM. Source: Biotechnology and Bioengineering. 2000 October 20; 70(2): 167-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10972928
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Osmotic nephrosis due to high-dose immunoglobulin therapy containing sucrose (but not with glycine) in a patient with immunoglobulin A nephritis. Author(s): Hansen-Schmidt S, Silomon J, Keller F. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1996 September; 28(3): 451-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8804246
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Osteogenesis imperfecta phenotypes resulting from serine for glycine substitutions in the alpha2(I) collagen chain. Author(s): Nuytinck L, Wettinck K, Freund M, Van Maldergem L, Fabry G, De Paepe A. Source: European Journal of Human Genetics : Ejhg. 1997 May-June; 5(3): 161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9272740
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Overexpression of glycine-extended gastrin in transgenic mice results in increased colonic proliferation. Author(s): Koh TJ, Dockray GJ, Varro A, Cahill RJ, Dangler CA, Fox JG, Wang TC. Source: The Journal of Clinical Investigation. 1999 April; 103(8): 1119-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10207163
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Oxoproline kinetics and oxoproline urinary excretion during glycine- or sulfur amino acid-free diets in humans. Author(s): Metges CC, Yu YM, Cai W, Lu XM, Wong S, Regan MM, Ajami A, Young VR. Source: American Journal of Physiology. Endocrinology and Metabolism. 2000 May; 278(5): E868-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10780943
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Pharmacokinetics and disposition of a novel NMDA glycine site antagonist (UK240,455) in rats, dogs and man. Author(s): Webster R, Cole S, Gedge J, Roffey S, Walker D, Wild W. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 2003 May; 33(5): 541-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746109
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Pitfalls in the diagnosis of glycine encephalopathy (non-ketotic hyperglycinemia). Author(s): Korman SH, Gutman A. Source: Developmental Medicine and Child Neurology. 2002 October; 44(10): 712-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12418798
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Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Author(s): Sumiyoshi T, Anil AE, Jin D, Jayathilake K, Lee M, Meltzer HY. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2004 March; 7(1): 1-8. Epub 2004 January 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720317
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Porous polymer scaffolds surface-modified with arginine-glycine-aspartic acid enhance bone cell attachment and differentiation in vitro. Author(s): Hu Y, Winn SR, Krajbich I, Hollinger JO. Source: Journal of Biomedical Materials Research. 2003 March 1; 64A(3): 583-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12579573
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Potentiation of inhibitory glycinergic neurotransmission by Zn2+: a synergistic interplay between presynaptic P2X2 and postsynaptic glycine receptors. Author(s): Laube B. Source: The European Journal of Neuroscience. 2002 September; 16(6): 1025-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12383231
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Preliminary investigation of high-dose oral glycine on serum levels and negative symptoms in schizophrenia: an open-label trial. Author(s): Leiderman E, Zylberman I, Zukin SR, Cooper TB, Javitt DC. Source: Biological Psychiatry. 1996 February 1; 39(3): 213-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8837983
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Probing the topology of the glycine receptor by chemical modification coupled to mass spectrometry. Author(s): Leite JF, Cascio M. Source: Biochemistry. 2002 May 14; 41(19): 6140-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994009
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Propofol restores the function of "hyperekplexic" mutant glycine receptors in Xenopus oocytes and mice. Author(s): O'Shea SM, Becker L, Weiher H, Betz H, Laube B. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2004 March 3; 24(9): 2322-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14999083
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Quantification of ineffective erythropoiesis in megaloblastic anaemia by determination of endogenous production of 14CO after administration of glycine-214C. Author(s): Lindahl J. Source: Scand J Haematol. 1980 April; 24(4): 281-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7414299
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Quantitation of glycine in plasma and urine by chemical ionization mass fragmentography. Author(s): Petty F, Tucker HN, Molinary SV, Flynn NW, Wander JD. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1976 January 2; 66(1): 111-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1261033
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Quantitative analysis of urinary glycine conjugates by high performance liquid chromatography: excretion of hippuric acid and methylhippuric acids in the urine of subjects exposed to vapours of toluene and xylenes. Author(s): Ogata M, Taguchi T. Source: International Archives of Occupational and Environmental Health. 1986; 58(2): 121-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3744566
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Quantitative aspects of glycine and alanine nitrogen metabolism in postabsorptive young men: effects of level of nitrogen and dispensable amino acid intake. Author(s): Yu YM, Yang RD, Matthews DE, Wen ZM, Burke JF, Bier DM, Young VR. Source: The Journal of Nutrition. 1985 March; 115(3): 399-410. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3973749
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Rapid glycine absorption secondary to pressurization of irrigation fluid during transcervical endometrial resection. Author(s): Shah T, Evans A, Brown M. Source: European Journal of Anaesthesiology. 2001 March; 18(3): 197-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11298182
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Recent developments in glycine antagonists. Author(s): Antolini M, Donati D, Micheli F. Source: Curr Opin Investig Drugs. 2000 October; 1(2): 230-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11249579
102
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Recurrent mutations in P- and T-proteins of the glycine cleavage complex and a novel T-protein mutation (N145I): a strategy for the molecular investigation of patients with nonketotic hyperglycinemia (NKH). Author(s): Toone JR, Applegarth DA, Coulter-Mackie MB, James ER. Source: Molecular Genetics and Metabolism. 2001 April; 72(4): 322-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11286506
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Reduced expression of the neuron restrictive silencer factor permits transcription of glycine receptor alpha1 subunit in small-cell lung cancer cells. Author(s): Gurrola-Diaz C, Lacroix J, Dihlmann S, Becker CM, von Knebel Doeberitz M. Source: Oncogene. 2003 August 28; 22(36): 5636-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944912
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Reduced reperfusion injury by glycine in a porcine liver transplantation model with non-heart-beating donors. Author(s): Barros-Schelotto P, Net M, Valero R, Ruiz A, Almenara R, Capdevila L, Sugranes G, Suarez-Crivaro F, Lopez-Boado MA, Pellegrino A, Deulofeu R, Miquel R, Taura P, Manyalich M, Garcia-Valdecasas JC. Source: Transplantation Proceedings. 2002 June; 34(4): 1114-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072291
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Reintroduction of a characterized Mit tRNA glycine mutation into yeast mitochondria provides a new tool for the study of human neurodegenerative diseases. Author(s): Rohou H, Francisci S, Rinaldi T, Frontali L, Bolotin-Fukuhara M. Source: Yeast (Chichester, England). 2001 February; 18(3): 219-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180455
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Relaxation of glycine receptor and onconeural gene transcription control in NRSF deficient small cell lung cancer cell lines. Author(s): Neumann SB, Seitz R, Gorzella A, Heister A, Doeberitz MK, Becker CM. Source: Brain Research. Molecular Brain Research. 2004 January 5; 120(2): 173-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14741407
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Role of charged residues in coupling ligand binding and channel activation in the extracellular domain of the glycine receptor. Author(s): Absalom NL, Lewis TM, Kaplan W, Pierce KD, Schofield PR. Source: The Journal of Biological Chemistry. 2003 December 12; 278(50): 50151-7. Epub 2003 October 02. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14525990
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Role of glycine-534 and glycine-1179 of human multidrug resistance protein (MDR1) in drug-mediated control of ATP hydrolysis. Author(s): Szakacs G, Ozvegy C, Bakos E, Sarkadi B, Varadi A. Source: The Biochemical Journal. 2001 May 15; 356(Pt 1): 71-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11336637
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Role of non-glycine residues in left-handed helical conformation for the conformational stability of human lysozyme. Author(s): Takano K, Yamagata Y, Yutani K. Source: Proteins. 2001 August 15; 44(3): 233-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11455596
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Simple and accurate determination of bisphenol A in red blood cells prepared with basic glycine buffer using liquid chromatography-electrochemical detection. Author(s): Sajiki J. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 January 15; 783(2): 367-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12482479
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Single channel analysis of conductance and rectification in cation-selective, mutant glycine receptor channels. Author(s): Moorhouse AJ, Keramidas A, Zaykin A, Schofield PR, Barry PH. Source: The Journal of General Physiology. 2002 May; 119(5): 411-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11981021
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Statistical coassembly of glycine receptor alpha1 wildtype and the hyperekplexia mutant alpha1(P250T) in HEK 293 cells: impaired channel function is not dominant in the recombinant system. Author(s): Breitinger HG, Becker CM. Source: Neuroscience Letters. 2002 October 4; 331(1): 21-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359314
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Stoichiometry of recombinant heteromeric glycine receptors revealed by a pore-lining region point mutation. Author(s): Burzomato V, Groot-Kormelink PJ, Sivilotti LG, Beato M. Source: Receptors & Channels. 2003; 9(6): 353-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698963
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Structure and function of the glycine receptor and related nicotinicoid receptors. Author(s): Cascio M. Source: The Journal of Biological Chemistry. 2004 May 7; 279(19): 19383-6. Epub 2004 March 15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023997
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Structure of the human alpha 2 subunit gene of the glycine receptor--use of vectorette and Alu-exon PCR. Author(s): Monani U, Burghes AH. Source: Genome Research. 1996 December; 6(12): 1200-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8973915
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Structure, function and regulation of glycine neurotransporters. Author(s): Aragon C, Lopez-Corcuera B. Source: European Journal of Pharmacology. 2003 October 31; 479(1-3): 249-62. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14612155
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Substitution of arginine for glycine at position 154 of the alpha 1 chain of type I collagen in a variant of osteogenesis imperfecta: comparison to previous cases with the same mutation. Author(s): Zhuang J, Tromp G, Kuivaniemi H, Castells S, Prockop DJ. Source: American Journal of Medical Genetics. 1996 January 11; 61(2): 111-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8669434
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Substitution of glycine-661 by serine in the alpha1(I) and alpha2(I) chains of type I collagen results in different clinical and biochemical phenotypes. Author(s): Nuytinck L, Dalgleish R, Spotila L, Renard JP, Van Regemorter N, De Paepe A. Source: Human Genetics. 1996 March; 97(3): 324-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8786074
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Synthesis, characterization, and in vitro antitumor activity of osteotropic diam(m)ineplatinum(II) complexes bearing a N,N-bis(phosphonomethyl)glycine ligand. Author(s): Galanski M, Slaby S, Jakupec MA, Keppler BK. Source: Journal of Medicinal Chemistry. 2003 November 6; 46(23): 4946-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14584945
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The activation mechanism of alpha1 homomeric glycine receptors. Author(s): Beato M, Groot-Kormelink PJ, Colquhoun D, Sivilotti LG. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2004 January 28; 24(4): 895-906. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14749434
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The activity of a blood type B specific exoglycosidase from Glycine max. Author(s): Hobbs L, Mitra M, Phillips R, Smith D. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1996 March 29; 247(1-2): 7-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8920223
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The contribution of proline 250 (P-2') to pore diameter and ion selectivity in the human glycine receptor channel. Author(s): Lee DJ, Keramidas A, Moorhouse AJ, Schofield PR, Barry PH. Source: Neuroscience Letters. 2003 November 20; 351(3): 196-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623139
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The effect of an arginine-glycine-aspartic acid peptide and hyaluronate synthetic matrix on epithelialization of meshed skin graft interstices. Author(s): Cooper ML, Hansbrough JF, Polarek JW. Source: The Journal of Burn Care & Rehabilitation. 1996 March-April; 17(2): 108-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8675500
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The effect of intracervical vasopressin on the systemic absorption of glycine during hysteroscopic endometrial ablation. Author(s): Ankum WM. Source: Obstetrics and Gynecology. 1996 November; 88(5): 901-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8885940
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The mechanisms for regulating absorption of Fe bis-glycine chelate and Fe-ascorbate in caco-2 cells are similar. Author(s): Mazariegos DI, Pizarro F, Olivares M, Nunez MT, Arredondo M. Source: The Journal of Nutrition. 2004 February; 134(2): 395-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747678
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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872849
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The role of glycine residues in the function of human organic anion transporter 4. Author(s): Zhou F, Tanaka K, Pan Z, Ma J, You G. Source: Molecular Pharmacology. 2004 May; 65(5): 1141-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15102942
106
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The water effect on allosteric regulation of hemoglobin probed in water/glucose and water/glycine solutions. Author(s): Colombo MF, Bonilla-Rodriguez GO. Source: The Journal of Biological Chemistry. 1996 March 1; 271(9): 4895-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8617761
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Transport of glycine in the brush border and basal cell membrane vesicles of the human term placenta. Author(s): Anand RJ, Kanwar U, Sanyal SN. Source: Biochem Mol Biol Int. 1996 February; 38(1): 21-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8932515
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Ulex europaeus I and glycine max bind to the human olfactory bulb. Author(s): Nagao M, Oka N, Kamo H, Akiguchi I, Kimura J. Source: Neuroscience Letters. 1993 December 24; 164(1-2): 221-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8152605
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Unconjugated, glycine-conjugated, taurine-conjugated bile acid nonsulfates and sulfates in urine of young infants with cholestasis. Author(s): Tazawa Y, Yamada M, Nakagawa M, Konno Y, Tada K. Source: Acta Paediatr Scand. 1984 May; 73(3): 392-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6741539
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Unusual MR spectroscopic imaging pattern of an astrocytoma: lack of elevated choline and high myo-inositol and glycine levels. Author(s): Londono A, Castillo M, Armao D, Kwock L, Suzuki K. Source: Ajnr. American Journal of Neuroradiology. 2003 May; 24(5): 942-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748098
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Up-regulation of integrin alpha5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine- amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells. Author(s): Chikama T, Nakamura M, Nishida T. Source: Biochemical and Biophysical Research Communications. 1999 February 24; 255(3): 692-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10049772
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Uptake of gamma-aminobutyric acid and glycine by synaptosomes from postmortem human brain. Author(s): Hardy JA, Barton A, Lofdahl E, Cheetham SC, Johnston GA, Dodd PR. Source: Journal of Neurochemistry. 1986 August; 47(2): 460-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3734788
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Uptake of glycine by human kidney cortex. Author(s): Roth KS, Holtzapple P, Genel M, Segal S. Source: Metabolism: Clinical and Experimental. 1979 June; 28(6): 677-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=449705
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Uptake of tritiated glycine into neurons of the human retina. Author(s): Ehinger B. Source: Experientia. 1972 September 15; 28(9): 1042-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4579104
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Urinary excretion of 5-L-oxoproline (pyroglutamic acid) is increased during recovery from severe childhood malnutrition and responds to supplemental glycine. Author(s): Persaud C, Forrester T, Jackson AA. Source: The Journal of Nutrition. 1996 November; 126(11): 2823-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8914954
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Urinary excretion of 5-oxoproline (pyroglutamic aciduria) as an index of glycine insufficiency in normal man. Author(s): Jackson AA, Badaloo AV, Forrester T, Hibbert JM, Persaud C. Source: The British Journal of Nutrition. 1987 September; 58(2): 207-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3676243
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Use of 1.5% glycine as a nonconductive fluid medium for arthroscopic electrosurgery. Author(s): Bert JM. Source: Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 1987; 3(4): 248-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3689522
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Valine/glycine ratio in newborn infants. Author(s): Hibbard ED, Kenna AP. Source: Biology of the Neonate. 1975; 27(1-2): 56-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1148350
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Valyl-alanyl-prolyl-glycine (VAPG) serves as a quantitative marker for human elastins. Author(s): Price LS, Roos PJ, Shively VP, Sandberg LB. Source: Matrix. 1993 July; 13(4): 307-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8412988
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Variant creatine kinase isoenzyme band induced by glycine. Author(s): Olson J, Evancho J, Randall J, Oei TO. Source: Clinical Chemistry. 1982 November; 28(11): 2333. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7127793
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Vasopressin and amino acid concentrations in serum following absorption of irrigating fluid containing glycine and ethanol. Author(s): Hahn RG, Rundgren M. Source: British Journal of Anaesthesia. 1989 September; 63(3): 337-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2803891
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Vasopressin and cortisol levels in response to glycine infusion. Author(s): Hahn RG, Stalberg HP, Gustafsson SA. Source: Scandinavian Journal of Urology and Nephrology. 1991; 25(2): 121-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1871556
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Venous embolism of diathermy evolved gases complicating endometrial ablation using glycine irrigant. Author(s): Hebbard PD. Source: Anaesthesia and Intensive Care. 1998 February; 26(1): 112-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9513679
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Visual disturbances, serum glycine levels and transurethral resection of the prostate. Author(s): Mizutani AR, Parker J, Katz J, Schmidt J. Source: The Journal of Urology. 1990 September; 144(3): 697-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2388330
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Visual evoked potentials and changes in serum glycine concentration during transurethral resection of the prostate. Author(s): Casey WF, Hannon V, Cunningham A, Heaney J. Source: British Journal of Anaesthesia. 1988 April; 60(5): 525-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3377929
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Vitamin B12 decreases, but does not normalize, homocysteine and methylmalonic acid in end-stage renal disease: a link with glycine metabolism and possible explanation of hyperhomocysteinemia in end-stage renal disease. Author(s): Hyndman ME, Manns BJ, Snyder FF, Bridge PJ, Scott-Douglas NW, Fung E, Parsons HG. Source: Metabolism: Clinical and Experimental. 2003 February; 52(2): 168-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12601627
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Water and electrolytes in muscle tissue and free amino acids in muscle and plasma in connection with transurethral resection of the prostate. II. Isotonic 2.2% glycine solution as an irrigating fluid. Author(s): Norlen H, Dimberg M, Allgen LG, Vinnars E. Source: Scandinavian Journal of Urology and Nephrology. 1990; 24(2): 95-101. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1694040
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Whole body de novo amino acid synthesis in type I (insulin-dependent) diabetes studied with stable isotope-labeled leucine, alanine, and glycine. Author(s): Robert JJ, Beaufrere B, Koziet J, Desjeux JF, Bier DM, Young VR, Lestradet H. Source: Diabetes. 1985 January; 34(1): 67-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3880550
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Whole body protein turnover, studied with 15N-glycine, and muscle protein breakdown in mildly obese subjects during a protein-sparing diet and a brief total fast. Author(s): Winterer J, Bistrian BR, Bilmazes C, Blackburn GL, Young VR. Source: Metabolism: Clinical and Experimental. 1980 June; 29(6): 575-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7382824
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Whole-body protein turnover in man determined in three hours with oral or intravenous 15N-glycine and enrichment in urinary ammonia. Author(s): Jackson AA, Persaud C, Badaloo V, de Benoist B. Source: Hum Nutr Clin Nutr. 1987 July; 41(4): 263-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3623989
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Why glycine transporters have different stoichiometries. Author(s): Supplisson S, Roux MJ. Source: Febs Letters. 2002 October 2; 529(1): 93-101. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12354619
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Widespread expression of gephyrin, a putative glycine receptor-tubulin linker protein, in rat brain. Author(s): Kirsch J, Betz H. Source: Brain Research. 1993 September 10; 621(2): 301-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8242343
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X-linked retinitis pigmentosa in two families with a missense mutation in the RPGR gene and putative change of glycine to valine at codon 60. Author(s): Fishman GA, Grover S, Jacobson SG, Alexander KR, Derlacki DJ, Wu W, Buraczynska M, Swaroop A. Source: Ophthalmology. 1998 December; 105(12): 2286-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9855162
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X-ray structure determination at 2.6-A resolution of a lipoate-containing protein: the H-protein of the glycine decarboxylase complex from pea leaves. Author(s): Pares S, Cohen-Addad C, Sieker L, Neuburger M, Douce R. Source: Proceedings of the National Academy of Sciences of the United States of America. 1994 May 24; 91(11): 4850-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8197146
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Zinc potentiation of the glycine receptor chloride channel is mediated by allosteric pathways. Author(s): Lynch JW, Jacques P, Pierce KD, Schofield PR. Source: Journal of Neurochemistry. 1998 November; 71(5): 2159-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9798943
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Zn2+ inhibits glycine transport by glycine transporter subtype 1b. Author(s): Ju P, Aubrey KR, Vandenberg RJ. Source: The Journal of Biological Chemistry. 2004 May 28; 279(22): 22983-91. Epub 2004 March 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15031290
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CHAPTER 2. NUTRITION AND GLYCINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and glycine.
Finding Nutrition Studies on Glycine 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 “glycine” (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 glycine: •
Nutrition of the fetus and the premature infant. Author(s): University of Colorado School of Medicine, Denver, CO. Source: Battaglia, F.C. Thureen, P.J. Diabetes-care (USA). (August 1998). volume 21(suppl.2) page B70-B74.
Additional consumer oriented references include: •
The Journal of Biological Chemistry, Volume 134, June 1940: Studies in protein metabolism. XIV. The chemical interaction of dietary glycine and body proteins in rats. By S. Ratner, D. Rittenberg, Albert S. Keston, and Rudolf Schoenheimer. Source: Ratner, S Rittenberg, D Keston, A S Schoenheimer, R Nutr-Revolume 1987 October; 45(10): 310-2 0029-6643
The following information is typical of that found when using the “Full IBIDS Database” to search for “glycine” (or a synonym): •
A glycine receptor antagonist, strychnine, blocked NMDA receptor activation in the neonatal mouse neocortex. Author(s): Department of Neurochemistry, National Institute of Neuroscience, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. Source: Miyakawa, N Uchino, S Yamashita, T Okada, H Nakamura, T Kaminogawa, S Miyamoto, Y Hisatsune, T Neuroreport. 2002 September 16; 13(13): 1667-73 0959-4965
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A spatial model of the glycine site of the NR1 subunit of NMDA-receptor and ligand docking. Author(s): Moscow State University, Vorob'evy gory, Moscow, 119899 Russia. Source: Tikhonova, I G Baskin, I I Palyulin, V A Zefirov, N S Dokl-Biochem-Biophys. 2002 Jan-February; 382: 67-70 1607-6729
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Cloning and functional characterization of two glycine receptor alpha-subunits from the perch retina. Author(s): Ruhr-University Bochum, Department of Cell Physiology, ND4, D-44780 Bochum, Germany. Source: Gisselmann, G Galler, A Friedrich, F Hatt, H Bormann, J Eur-J-Neurosci. 2002 July; 16(1): 69-80 0953-816X
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Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and nonrandomized trial. Author(s): Virgen de la Macarena Hospital, Sevilla, Spain. Source: Albert, A Altabre, C Baro, F Buendia, E Cabero, A Cancelo, M J Castelo Branco, C Chantre, P Duran, M Haya, J Imbert, P Julia, D Lanchares, J L Llaneza, P Manubens, M Minano, A Quereda, F Ribes, C Vazquez, F Phytomedicine. 2002 March; 9(2): 85-92 09447113
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Electrophysiological evidence for expression of glycine receptors in freshly isolated neurons from nucleus accumbens. Author(s): Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA, USA.
[email protected] Source: Martin, G Siggins, G R J-Pharmacol-Exp-Ther. 2002 September; 302(3): 1135-45 0022-3565
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Ethanol suppresses fast potentiation of glycine currents by glutamate. Author(s): Department of Anesthesiology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103-2714, USA. Source: Zhu, L Krnjevic, K Jiang, Z McArdle, J J Ye, J H J-Pharmacol-Exp-Ther. 2002 September; 302(3): 1193-200 0022-3565
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Neurogenesis of gasping does not require inhibitory transmission using GABA(A) or glycine receptors. Author(s): Department of Physiology, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03755, USA.
[email protected] Source: St John, W M Paton, J F Respir-Physiolo-Neurobiol. 2002 September 4; 132(3): 265-77 1569-9048
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New 2H-tetrahydro-1, 3, 5-thiadiazine-2-thiones incorporating glycine and glycinamide as potential antifungal agents. Author(s): Faculty of Pharmacy, Assiut University, Assiut-71526, Egypt. Source: Aboul Fadl, T Hussein, M A El Shorbagi, A N Khallil, A R Arch-Pharm(Weinheim). 2002 November; 335(9): 438-42 0365-6233
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Target alcohol/phenol release by cyclative cleavage using glycine as a safety catch linker. Author(s): Organic Division I, Indian Institute of Chemical Technology, Hyderabad 500 007, India. Source: Raghavan, S Rajender, A Chem-Commun-(Camb). 2002 August 7; (15): 1572-3 1359-7345
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to glycine; 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 Betaine Hydrochloride Source: Healthnotes, Inc.; www.healthnotes.com Betaine Hydrochloride Source: Prima Communications, Inc.www.personalhealthzone.com Creatine Source: Prima Communications, Inc.www.personalhealthzone.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Iron Alternative names: Ferrous Sulfate Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com Zinc Source: Prima Communications, Inc.www.personalhealthzone.com
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Food and Diet Ferrous Sulfate Source: Integrative Medicine Communications; www.drkoop.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND GLYCINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to glycine. 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 glycine 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 “glycine” (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 glycine: •
A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Author(s): Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. Source: Alternative Therapies in Health and Medicine. 2001 May-June; 7(3): 49-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11347285
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Anticonvulsant actions of LY 367385 ((+)-2-methyl-4-carboxyphenylglycine) and AIDA ((RS)-1-aminoindan-1,5-dicarboxylic acid). Author(s): Chapman AG, Yip PK, Yap JS, Quinn LP, Tang E, Harris JR, Meldrum BS. Source: European Journal of Pharmacology. 1999 February 26; 368(1): 17-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10096765
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Anticonvulsant activity of 3,4-dicarboxyphenylglycines in DBA/2 mice. Author(s): Moldrich RX, Beart PM, Jane DE, Chapman AG, Meldrum BS.
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Source: Neuropharmacology. 2001 April; 40(5): 732-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11311902 •
Antimutagenic activity of isoflavones from soybean seeds (Glycine max merrill). Author(s): Miyazawa M, Sakano K, Nakamura S, Kosaka H. Source: Journal of Agricultural and Food Chemistry. 1999 April; 47(4): 1346-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10563978
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Calcium ion involvement in growth inhibition of mechanically stressed soybean (Glycine max) seedlings. Author(s): Jones RS, Mitchell CA. Source: Physiologia Plantarum. 1989; 76: 598-602. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11538861
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Camptothecin delivery systems: enhanced efficacy and tumor accumulation of camptothecin following its conjugation to polyethylene glycol via a glycine linker. Author(s): Conover CD, Greenwald RB, Pendri A, Gilbert CW, Shum KL. Source: Cancer Chemotherapy and Pharmacology. 1998; 42(5): 407-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9771956
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Chronic high-dose glycine nutrition: effects on rat brain cell morphology. Author(s): Shoham S, Javitt DC, Heresco-Levy U. Source: Biological Psychiatry. 2001 May 15; 49(10): 876-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343684
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Competitive NMDA and strychnine-insensitive glycine-site antagonists disrupt prepulse inhibition. Author(s): Furuya Y, Ogura H. Source: Pharmacology, Biochemistry, and Behavior. 1997 August; 57(4): 909-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9259023
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Cross-species amplification of soybean (Glycine max) simple sequence repeats (SSRs) within the genus and other legume genera: implications for the transferability of SSRs in plants. Author(s): Peakall R, Gilmore S, Keys W, Morgante M, Rafalski A. Source: Molecular Biology and Evolution. 1998 October; 15(10): 1275-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9787434
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Cyanidin 3-O-beta-D-glucoside isolated from skin of black Glycine max and other anthocyanins isolated from skin of red grape induce apoptosis in human lymphoid leukemia Molt 4B cells. Author(s): Katsuzaki H, Hibasami H, Ohwaki S, Ishikawa K, Imai K, Date K, Kimura Y, Komiya T.
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Source: Oncol Rep. 2003 March-April; 10(2): 297-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12579261 •
Cyclic [beta]-1,6-1,3-Glucans of Bradyrhizobium japonicum USDA 110 Elicit Isoflavonoid Production in the Soybean (Glycine max) Host. Author(s): Miller KJ, Hadley JA, Gustine DL. Source: Plant Physiology. 1994 March; 104(3): 917-923. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12232136
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Cyclosporin A causes a hypermetabolic state and hypoxia in the liver: prevention by dietary glycine. Author(s): Zhong Z, Li X, Yamashina S, von Frankenberg M, Enomoto N, Ikejima K, Kolinsky M, Raleigh JA, Thurman RG. Source: The Journal of Pharmacology and Experimental Therapeutics. 2001 December; 299(3): 858-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11714869
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Dietary glycine blunts lung inflammatory cell influx following acute endotoxin. Author(s): Wheeler MD, Rose ML, Yamashima S, Enomoto N, Seabra V, Madren J, Thurman RG. Source: American Journal of Physiology. Lung Cellular and Molecular Physiology. 2000 August; 279(2): L390-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10926563
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Dietary glycine inhibits activation of nuclear factor kappa B and prevents liver injury in hemorrhagic shock in the rat. Author(s): Mauriz JL, Matilla B, Culebras JM, Gonzalez P, Gonzalez-Gallego J. Source: Free Radical Biology & Medicine. 2001 November 15; 31(10): 1236-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11705702
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Dietary glycine prevents peptidoglycan polysaccharide-induced reactive arthritis in the rat: role for glycine-gated chloride channel. Author(s): Li X, Bradford BU, Wheeler MD, Stimpson SA, Pink HM, Brodie TA, Schwab JH, Thurman RG. Source: Infection and Immunity. 2001 September; 69(9): 5883-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11500467
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Direct inhibition of glycine receptors by genistein, a tyrosine kinase inhibitor. Author(s): Huang RQ, Dillon GH. Source: Neuropharmacology. 2000 August 23; 39(11): 2195-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10963763
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Double-blind, placebo-controlled, crossover trial of glycine adjuvant therapy for treatment-resistant schizophrenia. Author(s): Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Horowitz A, Kelly D. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1996 November; 169(5): 610-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8932891
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Effect of folic acid and glycine supplementation on embryo development and folate metabolism during early pregnancy in pigs. Author(s): Guay F, Matte JJ, Girard CL, Palin MF, Giguere A, Laforest JP. Source: Journal of Animal Science. 2002 August; 80(8): 2134-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12211383
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Effect of folic acid plus glycine supplement on uterine prostaglandin and endometrial granulocyte-macrophage colony-stimulating factor expression during early pregnancy in pigs. Author(s): Guay F, Matte JJ, Girard CL, Palin MF, Giguere A, Laforest JP. Source: Theriogenology. 2004 January 15; 61(2-3): 485-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14662146
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Effect of glycine and vitamin supplementation on sulphur amino acid utilization by growing cattle. Author(s): Lambert BD, Titgemeyer EC, Loest CA, Johnson DE. Source: Journal of Animal Physiology and Animal Nutrition. 2004 August; 88(7-8): 288300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15274693
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Effect of spores of saprophytic fungi on phytoalexin accumulation in seeds of frogeye leaf spot and stem canker-resistant and -susceptible soybean (Glycine max L.) cultivars. Author(s): Garcez WS, Martins D, Garcez FR, Marques MR, Pereira AA, Oliveira LA, Rondon JN, Peruca AD. Source: Journal of Agricultural and Food Chemistry. 2000 August; 48(8): 3662-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10956166
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Effects of ginsenosides on glycine receptor alpha1 channels expressed in Xenopus oocytes. Author(s): Noh JH, Choi S, Lee JH, Betz H, Kim JI, Park CS, Lee SM, Nah SY. Source: Molecules and Cells. 2003 February 28; 15(1): 34-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661758
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Effects of glycine-metal compounds on Ascaridia galli-infected chickens expressed by a kinetic model. Author(s): Gabrashanska M, Teodorova SE, Galvez-Morros M, Mitov M.
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Source: Journal of Helminthology. 2004 March; 78(1): 25-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14972033 •
Effects of soybean (Glycine max) germination on biologically active components, nutritional values of seeds, and biological characteristics in rats. Author(s): Bau HM, Villaume C, Mejean L. Source: Die Nahrung. 2000 February; 44(1): 2-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10702991
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Efficacy and safety of a phytoestrogen preparation derived from Glycine max (L.) Merr in climacteric symptomatology: a multicentric, open, prospective and nonrandomized trial. Author(s): Albert A, Altabre C, Baro F, Buendia E, Cabero A, Cancelo MJ, CasteloBranco C, Chantre P, Duran M, Haya J, Imbert P, Julia D, Lanchares JL, Llaneza P, Manubens M, Minano A, Quereda F, Ribes C, Vazquez F. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2002 March; 9(2): 85-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11995954
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Enhancement of glycine receptor function by ethanol: role of phosphorylation. Author(s): Mascia MP, Wick MJ, Martinez LD, Harris RA. Source: British Journal of Pharmacology. 1998 September; 125(2): 263-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9786497
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Enhancement of TNF-alpha-induced apoptosis by immobilized arginine-glycineaspartate: involvement of a tyrosine kinase-dependent, MAP kinase-independent mechanism. Author(s): Moreno-Manzano V, Lucio-Cazana J, Konta T, Nakayama K, Kitamura M. Source: Biochemical and Biophysical Research Communications. 2000 October 22; 277(2): 293-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11032720
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Evaluation of selected food characteristics of three advanced lines of Nigerian soybean (Glycine max (L.) Merr.). Author(s): Giami SY. Source: Plant Foods for Human Nutrition (Dordrecht, Netherlands). 1997; 50(1): 17-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9198111
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Extracts from rhizomes of Cyperus articulatus (Cyperaceae) displace [3H]CGP39653 and [3H]glycine binding from cortical membranes and selectively inhibit NMDA receptor-mediated neurotransmission. Author(s): Bum EN, Meier CL, Urwyler S, Wang Y, Herrling PL.
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Source: Journal of Ethnopharmacology. 1996 November; 54(2-3): 103-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8953423 •
Flavonoid 6-hydroxylase from soybean (Glycine max L.), a novel plant P-450 monooxygenase. Author(s): Latunde-Dada AO, Cabello-Hurtado F, Czittrich N, Didierjean L, Schopfer C, Hertkorn N, Werck-Reichhart D, Ebel J. Source: The Journal of Biological Chemistry. 2001 January 19; 276(3): 1688-95. Epub 2000 October 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11027686
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Freezing of stallion semen with addition of glycine betaine. Author(s): Lindeberg H, Kurten A, Koskinen E, Katila T. Source: Zentralbl Veterinarmed A. 1999 March; 46(2): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10216445
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Functional characterization of a glycine 185-to-valine substitution in human Pglycoprotein by using a vaccinia-based transient expression system. Author(s): Ramachandra M, Ambudkar SV, Gottesman MM, Pastan I, Hrycyna CA. Source: Molecular Biology of the Cell. 1996 October; 7(10): 1485-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8898356
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GABAergic and glycinergic inhibition sharpens tuning for frequency modulations in the inferior colliculus of the big brown bat. Author(s): Koch U, Grothe B. Source: Journal of Neurophysiology. 1998 July; 80(1): 71-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9658029
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GABAergic and glycinergic neural inhibition in excitatory frequency tuning of bat inferior collicular neurons. Author(s): Lu Y, Jen PH. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2001 December; 141(3): 331-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11715077
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Gamma-aminobutyric acidergic and glycinergic inputs shape coding of amplitude modulation in the chinchilla cochlear nucleus. Author(s): Backoff PM, Shadduck Palombi P, Caspary DM. Source: Hearing Research. 1999 August; 134(1-2): 77-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10452378
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Genetic characterization of a mutant of Sinorhizobium fredii strain USDA208 with enhanced competitive ability for nodulation of soybean, Glycine max (L.) Merr. Author(s): Krishnan HB, Pueppke SG. Source: Fems Microbiology Letters. 1998 August 1; 165(1): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9711859
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Genistein directly blocks glycine receptors of rat neurons freshly isolated from the ventral tegmental area. Author(s): Zhu L, Jiang ZL, Krnjevic K, Wang FS, Ye JH. Source: Neuropharmacology. 2003 August; 45(2): 270-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842133
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Ginkgolides and glycine receptors: a structure-activity relationship study. Author(s): Jaracz S, Nakanishi K, Jensen AA, Stromgaard K. Source: Chemistry (Weinheim an Der Bergstrasse, Germany). 2004 March 19; 10(6): 150718. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15034895
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Glycine modulates the toxicity of benzyl acetate in F344 rats. Author(s): Abdo KM, Wenk ML, Harry GJ, Mahler J, Goehl TJ, Irwin RD. Source: Toxicologic Pathology. 1998 May-June; 26(3): 395-402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9608646
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Glycine receptor knock-in mice and hyperekplexia-like phenotypes: comparisons with the null mutant. Author(s): Findlay GS, Phelan R, Roberts MT, Homanics GE, Bergeson SE, Lopreato GF, Mihic SJ, Blednov YA, Harris RA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 September 3; 23(22): 8051-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954867
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Glycine-enhanced inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase-I by EDTA: a full account of the reported inhibition by commercial preparations of acidic fibroblast growth factor (FGF-1). Author(s): Lopez-Gomez J, Costas MJ, Meireles Ribeiro J, Fernandez A, Romero A, Avalos M, Cameselle JC. Source: Febs Letters. 1998 January 2; 421(1): 77-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9462844
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Glycine-extended gastrin exerts growth-promoting effects on human colon cancer cells. Author(s): Stepan VM, Sawada M, Todisco A, Dickinson CJ.
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Source: Molecular Medicine (Cambridge, Mass.). 1999 March; 5(3): 147-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10404512 •
Glycinergic and GABAergic inputs affect short-term suppression in the cochlear nucleus. Author(s): Backoff PM, Palombi PS, Caspary DM. Source: Hearing Research. 1997 August; 110(1-2): 155-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9282898
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High isoflavone content and estrogenic activity of 25 year-old Glycine max tissue cultures. Author(s): Federici E, Touche A, Choquart S, Avanti O, Fay L, Offord E, Courtois D. Source: Phytochemistry. 2003 October; 64(3): 717-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679094
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Hypolipidemic effect of Glycine tomentella root extract in hamsters. Author(s): Ko YJ, Wu YW, Lin WC. Source: The American Journal of Chinese Medicine. 2004; 32(1): 57-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15154285
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Improved energy coupling of human P-glycoprotein by the glycine 185 to valine mutation. Author(s): Omote H, Figler RA, Polar MK, Al-Shawi MK. Source: Biochemistry. 2004 April 6; 43(13): 3917-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15049699
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Improved method for gas chromatographic analysis of genistein and daidzein from soybean (Glycine max) seeds. Author(s): Ghosh P, Fenner GP. Source: Journal of Agricultural and Food Chemistry. 1999 September; 47(9): 3455-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10552671
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Incongruence in the diploid B-genome species complex of Glycine (Leguminosae) revisited: histone H3-D alleles versus chloroplast haplotypes. Author(s): Doyle JJ, Doyle JL, Brown AH. Source: Molecular Biology and Evolution. 1999 March; 16(3): 354-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10331262
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Increased sensitization of acoustic startle response in spasmodic mice with a mutation of the glycine receptor alpha1-subunit gene. Author(s): Plappert CF, Pilz PK, Becker K, Becker CM, Schnitzler HU.
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Source: Behavioural Brain Research. 2001 June; 121(1-2): 57-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11275284 •
Increased systolic blood pressure in rats induced by a maternal low-protein diet is reversed by dietary supplementation with glycine. Author(s): Jackson AA, Dunn RL, Marchand MC, Langley-Evans SC. Source: Clinical Science (London, England : 1979). 2002 December; 103(6): 633-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12444916
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Inhibition of beta(2) integrin-mediated leukocyte cell adhesion by leucine-leucineglycine motif-containing peptides. Author(s): Koivunen E, Ranta TM, Annila A, Taube S, Uppala A, Jokinen M, van Willigen G, Ihanus E, Gahmberg CG. Source: The Journal of Cell Biology. 2001 May 28; 153(5): 905-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11381078
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Involvement of cyanide-resistant and rotenone-insensitive pathways of mitochondrial electron transport during oxidation of glycine in higher plants. Author(s): Igamberdiev AU, Bykova NV, Gardestrom P. Source: Febs Letters. 1997 July 28; 412(2): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9256232
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Iontophoresis in vivo demonstrates a key role for GABA(A) and glycinergic inhibition in shaping frequency response areas in the inferior colliculus of guinea pig. Author(s): LeBeau FE, Malmierca MS, Rees A. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 September 15; 21(18): 7303-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549740
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Iron bioavailability in humans from breakfasts enriched with iron bis-glycine chelate, phytates and polyphenols. Author(s): Layrisse M, Garcia-Casal MN, Solano L, Baron MA, Arguello F, Llovera D, Ramirez J, Leets I, Tropper E. Source: The Journal of Nutrition. 2000 September; 130(9): 2195-9. Erratum In: J Nutr 2000 December; 130(12): 3106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10958812
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Isolation and characterization of an active compound from black soybean [Glycine max (L.) Merr.] and its effect on proliferation and differentiation of human leukemic U937 cells. Author(s): Liao HF, Chou CJ, Wu SH, Khoo KH, Chen CF, Wang SY.
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Source: Anti-Cancer Drugs. 2001 November; 12(10): 841-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11707652 •
Isolation of a French bean (Phaseolus vulgaris L.) homolog to the beta-glucan elicitorbinding protein of soybean (Glycine max L.). Author(s): Mithofer A, Fliegmann J, Ebel J. Source: Biochimica Et Biophysica Acta. 1999 April 14; 1418(1): 127-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10209217
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IV glycine and oral D-cycloserine effects on plasma and CSF amino acids in healthy humans. Author(s): D'Souza DC, Gil R, Cassello K, Morrissey K, Abi-Saab D, White J, Sturwold R, Bennett A, Karper LP, Zuzarte E, Charney DS, Krystal JH. Source: Biological Psychiatry. 2000 March 1; 47(5): 450-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10704956
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Ivermectin, an unconventional agonist of the glycine receptor chloride channel. Author(s): Shan Q, Haddrill JL, Lynch JW. Source: The Journal of Biological Chemistry. 2001 April 20; 276(16): 12556-64. Epub 2001 January 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11278873
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Mice with glycine receptor subunit mutations are both sensitive and resistant to volatile anesthetics. Author(s): Quinlan JJ, Ferguson C, Jester K, Firestone LL, Homanics GE. Source: Anesthesia and Analgesia. 2002 September; 95(3): 578-82, Table of Contents. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12198041
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Natural polyamines inhibit soybean (Glycine max) lipoxygenase-1, but not the lipoxygenase-2 isozyme. Author(s): Maccarrone M, Baroni A, Finazzi-Agro A. Source: Archives of Biochemistry and Biophysics. 1998 August 1; 356(1): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9681988
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Novel aminopeptidase specific for glycine from Actinomucor elegans. Author(s): Ito K, Ma X, Azmi N, Huang HS, Fujii M, Yoshimoto T. Source: Bioscience, Biotechnology, and Biochemistry. 2003 January; 67(1): 83-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12619677
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Obese women on a low energy rice and bean diet: effects of leucine, arginine or glycine supplementation on protein turnover. Author(s): Marchini JS, Lambertini CR, Ferriolli E, Dutra de Oliveira JE.
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Source: Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas / Sociedade Brasileira De Biofisica. [et Al.]. 2001 October; 34(10): 1277-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11593302 •
Okadaic acid-induced, naringin-sensitive phosphorylation of glycine Nmethyltransferase in isolated rat hepatocytes. Author(s): Moller MT, Samari HR, Fengsrud M, Stromhaug PE, oStvold AC, Seglen PO. Source: The Biochemical Journal. 2003 July 15; 373(Pt 2): 505-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697024
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Oral administration of glycine and polyamine receptor antagonists blocks ethanol withdrawal seizures. Author(s): Kotlinska J, Liljequist S. Source: Psychopharmacology. 1996 October; 127(3): 238-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8912402
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Oxalate content of soybean seeds (Glycine max: Leguminosae), soyfoods, and other edible legumes. Author(s): Massey LK, Palmer RG, Horner HT. Source: Journal of Agricultural and Food Chemistry. 2001 September; 49(9): 4262-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11559120
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Permeabilization of metabolites from biologically viable soybeans (Glycine max). Author(s): Wang HY, Komolpis K, Kaufman PB, Malakul P, Shotipruk A. Source: Biotechnology Progress. 2001 May-June; 17(3): 424-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386861
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Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part I-anti-cancer activity. Author(s): Suthar AC, Banavalikar MM, Biyani MK. Source: Indian J Exp Biol. 2001 June; 39(6): 511-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562011
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Pharmacological activities of Genistein, an isoflavone from soy (Glycine max): part II-anti-cholesterol activity, effects on osteoporosis & menopausal symptoms. Author(s): Suthar AC, Banavalikar MM, Biyani MK. Source: Indian J Exp Biol. 2001 June; 39(6): 520-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562012
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Phylogenetic utility of histone H3 intron sequences in the perennial relatives of soybean (Glycine: Leguminosae). Author(s): Doyle JJ, Kanazin V, Shoemaker RC.
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Source: Molecular Phylogenetics and Evolution. 1996 December; 6(3): 438-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8975698 •
Potassium fertilization effects on isoflavone concentrations in soybean [Glycine max (L.) Merr.]. Author(s): Vyn TJ, Yin X, Bruulsema TW, Jackson CJ, Rajcan I, Brouder SM. Source: Journal of Agricultural and Food Chemistry. 2002 June 5; 50(12): 3501-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12033818
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Radiation-induced enhancement of antioxidant contents of soybean (Glycine max Merrill). Author(s): Variyar PS, Limaye A, Sharma A. Source: Journal of Agricultural and Food Chemistry. 2004 June 2; 52(11): 3385-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15161202
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Reduction in the mechanonociceptive response by intrathecal administration of glycine and related compounds. Author(s): Simpson RK Jr, Gondo M, Robertson CS, Goodman JC. Source: Neurochemical Research. 1996 October; 21(10): 1221-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8923484
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Role of formaldehyde in direct formation of glycine and serine in bean leaves. Author(s): Nosticzius A. Source: Acta Biol Hung. 1998; 49(2-4): 193-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526961
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Soyasapogenol A and B distribution in soybean (Glycine max L. Merr.) in relation to seed physiology, genetic variability, and growing location. Author(s): Rupasinghe HP, Jackson CJ, Poysa V, Di Berardo C, Bewley JD, Jenkinson J. Source: Journal of Agricultural and Food Chemistry. 2003 September 24; 51(20): 5888-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13129290
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Spectral integration in the inferior colliculus: role of glycinergic inhibition in response facilitation. Author(s): Wenstrup J, Leroy SA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2001 February 1; 21(3): Rc124. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11157095
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Structural and functional investigations on the role of zinc in bifunctional rat peptidylglycine alpha-amidating enzyme. Author(s): Bell J, Ash DE, Snyder LM, Kulathila R, Blackburn NJ, Merkler DJ.
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Source: Biochemistry. 1997 December 23; 36(51): 16239-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9405058 •
Structural cell-wall proteins in protoxylem development: evidence for a repair process mediated by a glycine-rich protein. Author(s): Ryser U, Schorderet M, Zhao GF, Studer D, Ruel K, Hauf G, Keller B. Source: The Plant Journal : for Cell and Molecular Biology. 1997 July; 12(1): 97-111. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9263454
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Synthesis of [Gly-1]RA-VII, [Gly-2]RA-VII, and [Gly-4]RA-VII. Glycine-containing analogues of RA-VII, an antitumor bicyclic hexapeptide from Rubia plants. Author(s): Hitotsuyanagi Y, Hasuda T, Aihara T, Ishikawa H, Yamaguchi K, Itokawa H, Takeya K. Source: The Journal of Organic Chemistry. 2004 March 5; 69(5): 1481-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14987000
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Synthesis of 2-[4'-(ethylcarbamoyl)phenyl]-N-acetylglycine, the proposed structure for giganticine. Author(s): Suparpprom C, Vilaivan T. Source: Journal of Natural Products. 2001 August; 64(8): 1114-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11520243
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Terpene trilactones from Ginkgo biloba are antagonists of cortical glycine and GABA(A) receptors. Author(s): Ivic L, Sands TT, Fishkin N, Nakanishi K, Kriegstein AR, Stromgaard K. Source: The Journal of Biological Chemistry. 2003 December 5; 278(49): 49279-85. Epub 2003 September 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504293
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The effect of arginine or glycine supplementation on gastrointestinal function, muscle injury, serum amino acid concentrations and performance during a marathon run. Author(s): Buchman AL, O'Brien W, Ou CN, Rognerud C, Alvarez M, Dennis K, Ahn C. Source: International Journal of Sports Medicine. 1999 July; 20(5): 315-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10452229
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The effect of cell wall components on glycine-enhanced sterol side chain degradation to androstene derivatives by mycobacteria. Author(s): Sedlaczek L, Lisowska K, Korycka M, Rumijowska A, Ziolkowski A, Dlugonski J. Source: Applied Microbiology and Biotechnology. 1999 October; 52(4): 563-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10570804
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The frameshift mutation oscillator (Glra1(spd-ot)) produces a complete loss of glycine receptor alpha1-polypeptide in mouse central nervous system. Author(s): Kling C, Koch M, Saul B, Becker CM. Source: Neuroscience. 1997 May; 78(2): 411-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9145798
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The potential beneficial effect of glycine on the carbohydrate moieties of glycoproteins in an experimental model of alcohol-induced hepatotoxicity. Author(s): Senthilkumar R, Nalini N. Source: Journal of Medicinal Food. 2004 Spring; 7(1): 108-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15117562
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The temporal and spatial transcription pattern in root nodules of Vicia faba nodulin genes encoding glycine-rich proteins. Author(s): Schroder G, Fruhling M, Puhler A, Perlick AM. Source: Plant Molecular Biology. 1997 January; 33(1): 113-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9037164
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Therapeutic effect of arginine-glycine-aspartic acid peptides in acute renal injury. Author(s): Goligorsky MS, Noiri E, Kessler H, Romanov V. Source: Clinical and Experimental Pharmacology & Physiology. 1998 March-April; 25(34): 276-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9590583
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Vascular effects of a soy leaves (Glycine max) extract and kaempferol glycosides in isolated rat carotid arteries. Author(s): Ho HM, Chen R, Huang Y, Chen ZY. Source: Planta Medica. 2002 June; 68(6): 487-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12094288
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Vascular tissue-specific gene expression of xylem sap glycine-rich proteins in root and their localization in the walls of metaxylem vessels in cucumber. Author(s): Sakuta C, Satoh S. Source: Plant & Cell Physiology. 2000 May; 41(5): 627-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10929946
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to glycine; 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 Atherosclerosis Source: Healthnotes, Inc.; www.healthnotes.com Atherosclerosis and Heart Disease Prevention Source: Prima Communications, Inc.www.personalhealthzone.com Attention Deficit Disorder Source: Prima Communications, Inc.www.personalhealthzone.com Benign Prostatic Hyperplasia Source: Healthnotes, Inc.; www.healthnotes.com Benign Prostatic Hyperplasia Source: Integrative Medicine Communications; www.drkoop.com BPH Source: Integrative Medicine Communications; www.drkoop.com Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Common Cold/Sore Throat Source: Healthnotes, Inc.; www.healthnotes.com Epilepsy Source: Integrative Medicine Communications; www.drkoop.com
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High Homocysteine Source: Healthnotes, Inc.; www.healthnotes.com Prostate Enlargement Source: Integrative Medicine Communications; www.drkoop.com Schizophrenia Source: Healthnotes, Inc.; www.healthnotes.com Seizure Disorders Source: Integrative Medicine Communications; www.drkoop.com •
Chinese Medicine Dandouchi Alternative names: Fermented Soybean; Semen Sojae Preparatum Source: Chinese Materia Medica
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Herbs and Supplements Alanine Source: Healthnotes, Inc.; www.healthnotes.com Amino Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10003,00.html Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com Betaine (Trimethylglycine) Source: Healthnotes, Inc.; www.healthnotes.com Clozapine Source: Healthnotes, Inc.; www.healthnotes.com Glutamic Acid Source: Healthnotes, Inc.; www.healthnotes.com Glutathione Source: Healthnotes, Inc.; www.healthnotes.com Glutathione Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,854,00.html Glycine Source: Healthnotes, Inc.; www.healthnotes.com
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Glycyrrhiza Alternative names: Licorice; Glycyrrhiza glabra L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Gymnema Alternative names: Gurmar; Gymnema sylvestre Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Haloperidol Source: Healthnotes, Inc.; www.healthnotes.com Hydrastis Alternative names: Goldenseal; Hydrastis canadensis L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lecithin Source: Prima Communications, Inc.www.personalhealthzone.com Methionine Source: Healthnotes, Inc.; www.healthnotes.com Passiflora Alternative names: Passion Flower; Passiflora alata L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org TMG (trimethylglycine) Source: Prima Communications, Inc.www.personalhealthzone.com Trimethylglycine Alternative names: Betaine Source: Integrative Medicine Communications; www.drkoop.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 GLYCINE Overview In this chapter, we will give you a bibliography on recent dissertations relating to glycine. 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 “glycine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glycine, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Glycine 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 glycine. 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: •
Adaptation to growth light source by Glycine max (L.) Merr by Dijak, Margareta; PhD from University of Guelph (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65627
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Agronomic performance of indeterminate, semideterminate, and determinate soybeans, Glycine max (L.) Merr by Ablett, G. R; PhD from University of Guelph (Canada), 1987 http://wwwlib.umi.com/dissertations/fullcit/NL40515
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Effects of irrigation and fertilizer nitrogen on N2 fixation and yield in Phaseolus vulgaris L. and Glycine max (L.) Merrill by Smith, Donald Lawrence; PhD from University of Guelph (Canada), 1984 http://wwwlib.umi.com/dissertations/fullcit/NK65631
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Ethanol modulation of glycine receptors from hypoglossal motoneurons by Eggers, Erika Dawn, PhD from University of Washington, 2003, 106 pages http://wwwlib.umi.com/dissertations/fullcit/3079215
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Genome-wide search for glycine metabolism genes by Bataille, Alain R., MSc from Concordia University (Canada), 2003, 120 pages http://wwwlib.umi.com/dissertations/fullcit/MQ83846
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Interaction between the nitrogen fixing bacterium, Rhizobium japonicum and soybean, Glycine max L., involving specificity and recognition by Shantharam, Sivramiah; PhD from MEMORIAL University of Newfoundland (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK46788
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Lengthening of the filling period in soybeans, Glycine max (L) Merrill by Ahmed, Shabir; ADVDEG from University of Guelph (Canada), 1969 http://wwwlib.umi.com/dissertations/fullcit/NK06542
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Les petities proteines de choc thermique alpha B-cristalline et Hsp27: Une analyse de la mutation arginine en glycine responsable de la myopathie reliee aux filaments de desmine (French and English text) by Chavez Zobel, Aura Tionila, PhD from Universite Laval (Canada), 2003, 172 pages http://wwwlib.umi.com/dissertations/fullcit/NQ85498
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Mutation of sites in alpha subunits alters pharmacology and function of glycine and GABA(A) receptors by Findlay, Geoffrey Steven, PhD from the University of Texas at Austin, 2003, 262 pages http://wwwlib.umi.com/dissertations/fullcit/3116305
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Studies on transfer ribonucleic acids and aminoacyl-transfer ribonucleic acid synthetases of aromatic amino acids in soybean, Glycine max L by Swamy, G. Sivakumar; PhD from University of Windsor (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK49250
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The reaction of ninhydrin and 1,2-indanedione with glycine on Whatman's filter paper by Bliss, Mark Steven, MS from Michigan State University, 2003, 93 pages http://wwwlib.umi.com/dissertations/fullcit/1417817
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The role of phloem supply in soybean, Glycine max L. Merr., nodule function by Walsh, K. B; PhD from Queen's University at Kingston (Canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL40459
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The use of benzoylated deae-cellulose for the isolation of glycine transfer ribonucleic acids of yeast and for the development of new methods for sequence determination of nucleic acids by Warrington, Robert Charles; ADVDEG from the University of British Columbia (Canada), 1971 http://wwwlib.umi.com/dissertations/fullcit/NK08341
Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.
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CHAPTER 5. PATENTS ON GLYCINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “glycine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on glycine, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Glycine By performing a patent search focusing on glycine, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on glycine: •
Albumin-free Factor VIII formulations Inventor(s): Besman; Marc (Studio City, CA), Bjornson; Erik (Studio City, CA), Carpenter; John (Littleton, CO), Jameel; Feroz (Covina, CA), Kashi; Ramesh (Walnut, CA), Pikal; Michael (Mansfield Center, CT), Tchessalov; Serguei (Ashfor, CT) Assignee(s): Baxter International Inc. (Deerfield, IL), University of Connecticut (Farmington, CT) Patent Number: 6,586,573 Date filed: February 22, 2000 Abstract: A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent. Excerpt(s): Factor VIII is a protein found in blood plasma which acts as a cofactor in the cascade of reactions leading to blood coagulation. A deficiency in the amount of Factor VIII activity in the blood results in the clotting disorder known as hemophilia A, an inherited condition primarily affecting males. Hemophilia A is currently treated with therapeutic preparations of Factor VIII derived from human plasma or manufactured using recombinant DNA technology. Such preparations are administered either in response to a bleeding episode (on-demand therapy) or at frequent, regular intervals to prevent uncontrolled bleeding (prophylaxis). Factor VIII is known to be relatively unstable in therapeutic preparations. In blood plasma, Factor VIII is usually complexed with another plasma protein, von Willebrand factor (vWF), which is present in plasma in a large molar excess to Factor VIII and is believed to protect Factor VIII from premature degradation. Another circulating plasma protein, albumin, may also play a role in stabilizing Factor VIII in vivo. Currently marketed Factor VIII preparations therefore primarily rely on the use of albumin and/or vWF to stabilize Factor VIII during the manufacturing process and during storage. The albumin and vWF used in currently marketed Factor VIII preparations is derived from human blood plasma, however, and the use of such material has certain drawbacks. Because a large molar excess of albumin compared to Factor VIII is generally added in order to increase the stability of the Factor VIII in such preparations, it is difficult to characterize the Factor VIII protein itself in these preparations. The addition of human-derived albumin to Factor VIII is also perceived as being a disadvantage with respect to recombinantlyproduced Factor VIII preparations. This is because recombinantly-derived Factor VIII preparations, in the absence of such added albumin, would otherwise contain no
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human-derived proteins, and the theoretical risk of transmitting a virus would be reduced. Web site: http://www.delphion.com/details?pn=US06586573__ •
Antiperspirant or deodorant compositions Inventor(s): Mayes; Andrew Easson (Bedford, GB), Rawlings; Anthony Vincent (Bebington, GB), Watkinson; Allan (Bedford, GB) Assignee(s): Unilever Home & Personal Care USA division of Conopco, Inc. (Chicago, IL) Patent Number: 6,713,051 Date filed: June 18, 2002 Abstract: Antiperspirant compositions comprising an astringent aluminum or zirconium salt can suffer from perceived irritancy when applied topically, which can be ameliorated or overcome by incorporating within the composition a PPAR activating fatty acid and/or hydrolyzable precursor thereof such as a triglyceride or ester of the PPAR, especially in an amount selected in the range of from 0.5 to 10 wt %.The compositions advantageously comprise an activated aluminum salt or aluminumzirconium glycine complex. Excerpt(s): The invention relates to antiperspirant compositions intended for topical application to human skin. In particular, it relates to antiperspirant compositions comprising an agent that is capable of ameliorating or controlling skin irritancy. In many countries, civilised behaviour encourages people to take steps to prevent or control body odours or visible wet patches caused by sweating, particularly in the underarm or on clothing in the vicinity of the underarm. People in some countries prefer to control both sweat and odour, whereas in other countries control of odour alone is favoured. The antiperspirant market is currently dominated by topically applied products based on aluminium or zirconium salts which are intended to prevent, or at least control, localised perspiration at the skin surface, particularly on the underarm. Such formulations can often simultaneously provide a perceived degree of deodorancy. Web site: http://www.delphion.com/details?pn=US06713051__
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Composition for washing a polishing pad and method for washing a polishing pad Inventor(s): Ando; Michiaki (Tokyo, JP), Hattori; Masayuki (Tokyo, JP), Kawahashi; Nobuo (Tokyo, JP) Assignee(s): JSR Corporation (Tokyo, JP) Patent Number: 6,740,629 Date filed: June 11, 2002 Abstract: An object of the present invention is to provide a composition for washing a polishing pad which removes a water-insoluble compound which was separated from a surface to be polished during polishing, formed at least on the surface of a polishing pad, and comprised a metal ion ionized, and a method for washing a polishing pad using the same. The composition for washing a polishing pad of the present invention is obtained by, in the case a water-insoluble compound is a copper quinaldinic acid complex, blending ammonia as a component for rendering the water-insoluble
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compound water-soluble and glycine as a water-soluble complex forming component for forming a water-soluble complex with a copper ion, and stirring them. In addition, in a method for washing a polishing pad using the composition for washing a polishing pad, a polishing pad can be washed effectively, the productivity can be improved and, further, consumption of a polishing pad can be inhibited. Excerpt(s): The present invention relates to a composition for washing a polishing pad and a method for washing a polishing pad. More particularly, the present invention relates to a composition for washing a polishing pad which can effectively recover by inhibiting clogging generated in a polishing pad used for polishing wherein a waterinsoluble compound are formed during polishing, and consumption of the polishing pad, and a method for washing a polishing pad using the composition for washing a polishing pad. In chemical mechanical polishing (hereinafter, simply referred to as "CMP") used for polishing a semiconductor wafer and the like, polishing is performed by supplying a slurry (aqueous dispersion) containing abrasive or the like to an interface between a polishing pad and a surface to be polished. In the case of using a porous material such as expanded polyurethane or the like as a polishing pad, clogging due to a wastage is gradually proceeding, and a removal rate is reduced. For this reason, in order to recover the surface of the polishing pad to the state suitable for CMP, a step for renewing a polishing surface called as dressing is performed. This dressing is performed by sliding a polishing body (dresser) with diamond powder or the like attached thereto on the surface of the polishing pad. As this dressing, a method designated "in situ dressing", and a method designated "interval dressing" are known. The former is a method for dressing a region of a polishing pad which has not been polished during polishing, and the latter indicates a method for performing only dressing while polishing is stopped. In today's CMP, in situ dressing is performed if necessary and, however, interval dressing is usually essential. The interval dressing is performed for around 5 to 30 seconds every polishing of one material to be polished. For this reason, there is a certain limit to improvement in a product yield. Further, in the interval dressing, only physical dressing is performed or dressing is performed while cooling water is supplied. However, there is scarcely an attempt to also use the chemical effects. Web site: http://www.delphion.com/details?pn=US06740629__ •
Glycine and phaseolus.alpha.-D-galactosidases Inventor(s): Smith; Daniel S. (Columbia, MO), Walker; John C. (Columbia, MO) Assignee(s): The Curators of the University of Missouri (Columbia, MO) Patent Number: 6,630,339 Date filed: August 4, 2000 Abstract: A DNA (SEQ ID No.:2) and amino acid (SEQ ID No.:4) sequences of Glycine.alpha.-D-galactosidase are provided as well as the DNA sequence (SEQ ID No:5) and mature length amino acid sequence (SEQ ID No:7) of Phaseolus. Excerpt(s): The present invention relates to recombinant enzymes used in the conversion of type B erythrocytes to type O cells to render the cells useful for transfusion therapy. More specifically, the present invention provide novel recombinant galactosidases. The A, B, and H antigens are a clinically significant blood group (Landsteiner, 1901; Mollison et al, 1987). These antigens are terminal immunodominant monosaccharides on erythrocyte membrane glycoconjugates (Harmening, 1989). High densities of these epitopes are present on erythrocyte membranes and antibodies bound to these antigens
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readily fix complement (Economidou, et al, 1967; Romano and Mollison, 1987). Because these epitopes are ubiquitous in nature, immuno-potent and naturally occurring, complement fixing antibodies occur in individuals lacking these antigens, and transfusion of incompatible blood results in fatal hemolytic transfusion reactions (Fong et al, 1974; Schmidt, 1980). Complex sugar chains in glycolipids and glycoproteins have often been implicated in the growth and development of eukaryotes (Watanabe et al., 1976). In particular, complex sugar chains play an important part in the recognition of self in the immune system (Mollison et al., 1987). Exoglycosidases are enzymes which can modify carbohydrate membrane epitopes, thereby modulating the immune response (Goldstein et al., 1982). The.alpha.-D-galactosidase from Glycine is an enzyme that degrades the human blood group B epitope to the less immunogenic blood group H antigen also known as blood group O (Harpaz et al., 1977).alpha.-D-galactosidases [EC 3.2.1.22] are a common class of exoglycosidases. Although physical properties of these enzymes differ as a group, and the physiological significance of these enzymes are not clearly established, isozymes of.alpha.-D-galactosidase are common to many plant species (Flowers et al, 1979; Corchete, et al 1987). Several investigators have studied.alpha.-D-galactosidase from Coffea (Yatziv, 1971). There are reports that several isozymes exist for the Coffea.alpha.-D-galactosidase enzyme (Courtois, 1966). Web site: http://www.delphion.com/details?pn=US06630339__ •
Maize glycine rich protein promoter compositions and methods for use thereof Inventor(s): Laccetti; Lucille B. (Groton, CT), McElroy; David (Palo Alto, CA), Orozco, Jr.; Emil M. (West Grove, PA) Assignee(s): DeKalb Genetics Corporation (DeKalb, IL) Patent Number: 6,747,189 Date filed: March 21, 2000 Abstract: The current invention provides the Zea mays GRP (ZMGRP) promoter. 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 ZMGRP 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 Zea mays glycine rich protein promoter. An important aspect in the production of genetically engineered crops is obtaining sufficient levels of transgene expression in the appropriate plant tissues. 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 (Poszkowski et al., 1989; 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), nos (Ebert et al., 1987), Adh (Walker et al., 1987), and sucrose synthase (Yang & Russell, 1990).
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Web site: http://www.delphion.com/details?pn=US06747189__ •
Method for inhibiting 15-lipoxygenase with fermented Glycine max (L.) extract Inventor(s): Kung-Ming; William Lu (Taipei, TW) Assignee(s): Microbio Company, Ltd. (Taiwan, TW) Patent Number: 6,685,973 Date filed: April 17, 2002 Abstract: This invention relates to a use of a fermented Glycine max (L.) extract prepared by fermenting an aqueous Glycine max (L.) extract with at least one lactic acid bacteria together with at least one yeast, in inhibiting 15-lipoxygenase. In particular, the fermented Glycine max (L.) extract can be used in preventing and/or treating a disease in which 15-lipoxygenase inhibition is implicated in a subject, such as cardiovascular diseases, cancer, immune disorders, such as asthma, and inflammation and modulating the immune system. The invention also relates to a use of the fermented Glycine max (L.) extract in treating and/or preventing a microbe infection. Excerpt(s): The present application is a continuation in part application of U.S. patent application Ser. No. 09/812,579, filed on Mar. 21, 2001, now abandoned. This invention relates to a use of a fermented Glycine max (L.) extract in inhibiting 15-lipoxygenase, preventing and/or treating a disease in which 15-lipoxygenase inhibition is implicated in a subject, such as cardiovascular diseases, cancer, immune disorders, such as asthma and or inflammation, and modulating the immune system. The invention also relates to a use of the fermented Glycine max (L.) extract in preventing and/or treating a microbe infection. Lipoxygenases (LOX) are nonheme iron-containing enzyme that catalyze the oxygenation of certain polyunsaturated fatty acids such as lipoproteins. Several different lipoxygenase enzymes, e.g. LOX-5, LOX-12 and LOX-15, are known, each having a characteristic oxidation action. LOX-15 catalyzes the oxygenation of arachidonic and linoleic acids and has been implicated in the oxidative modification of low-density lipoproteins (LDL). Many researches reported that the LOX-15 is associated with coronary artery disease and atherosclerosis (Shen et al., J. Clin. Invest. 1996, Vol. 98, No. 10, pp. 2201-2208; Timo et al., 1995, Vol. 92 (11), pp. 3297-3303; Ravalli et al., 1995, Arteriosclerosis, Thrombosis and Vascular Biology, Vol. 15, No. 3, pp. 340-348; and Kuhn et al., 1997, J. Clin. Invest., Vol. 99, No. 5, pp. 888-893), cancer and inflammatory diseases Molecular Pharmacology, 56: 196-203; and Kamitani et al., 1998, the Journal of Biological Chemistry, Vol. 273, No. 34, pp. 21569-21577), and immune response (Kruisselbrink et al., 2001, Clin Exp Immunol, 126:2-8). Therefore, a substance having an efficacy in inhibiting LOX is useful as an agent for preventing or treating diseases associated with LOX. Web site: http://www.delphion.com/details?pn=US06685973__
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Method for producing fibronectin and fibrinogen compositions using a polyalkylene glycol and glycine or.beta.-alanine Inventor(s): Broermann; Ralf (Vienna, AT), Seelich; Thomas (Vienna, AT) Assignee(s): Baxter Aktiengesellschaft (Vienna, AT) Patent Number: 6,579,537 Date filed: February 10, 2000
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Abstract: A method of producing a pharmaceutical preparation comprising fibronectin and fibrinogen is disclosed. The method involves admixing into a starting solution of fibrinogen and fibronectin, in a single step, a precipitating composition comprising a polyalkylene glycol and at least one of glycine and.beta.-alanine which forms a precipitate. Next, the precipitate is collected and a pharmaceutical preparation is prepared from the precipitate. The pharmaceutical preparation has a fibronectin:fibrinogen ratio from about 0.02 to about 0.2. Excerpt(s): The present application claims priority to Austrian application number A 206/99, filed Feb. 12, 1999. The invention relates to a method for producing protein compositions comprising fibronectin and fibrinogen and, optionally, further ingredients as well as to protein compositions obtainable according to this method. Tissue adhesives based on fibrinogen ("fibrin adhesives") have been known for a long time. They serve for a seamless or suture-supporting connection of human or animal tissues or organ parts, for sealing wounds, haemostasis and assisting wound healing. Web site: http://www.delphion.com/details?pn=US06579537__ •
Method for the manufacture of Anagrelide Inventor(s): Lang; Philip C. (Toms River, NJ), Roth; Michael Joseph (Bolton, CA), Spencer; Roxanne P. (Plainsboro, NJ), Yeh; Wen-Lung (Thornhill, CA) Assignee(s): Shire US Inc. (Florence, KY) Patent Number: 6,653,500 Date filed: April 25, 2002 Abstract: Methods are provided for making Anagrelide base from 2,3dichlorobenzaldehyde. A method is also provided for making an intermediate compound ethyl N-(2,3-dichloro-6-nitrobenzyl)glycine from 2,3-dichlorobenzaldehyde and for reducing the glycine compound using either SnCl.sub.2 or a specially defined catalyst. A cyclization method to form Anagrelide base from the corresponding iminoquinazoline compound is further provided. Excerpt(s): The invention relates to 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin2(3H)-one (compound III), more commonly known as Anagrelide base and, more particularly, to a method for the manufacture of Anagrelide base. Anagrelide (6,7dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one, (compound III) is a potent blood platelet reducing agent. A number of U.S. Patents have issued on Anagrelide and its method of making including U.S. Pat. Nos. 3,932,407; 4,146,718; 4,208,521; 4,357,330; Re No. 31,617; and 5,801,245. These patents are incorporated herein by reference. The hydrochloride monohydrate Anagrelide salt (compound IV) is prepared by adding hydrochloric acid to a methanol slurry of Anagrelide base (compound III) and heating to reflux. The hydrochloride salt is then hydrated in a high humidity chamber. These two steps are time-consuming however, and the yield of hydrochloride salt can be poor due to competing acid hydrolysis of the lactam ring and methyl ester formation. After 15 minutes at reflux, the isolated yield is 62% and this decreases to 40% after 2 hours. Web site: http://www.delphion.com/details?pn=US06653500__
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Method of manufacturing lithium-manganese oxide for use in lithium secondary battery Inventor(s): Han; Yi Sup (Daejeon Kwangyeok-si, KR), Kim; Ho Gi (Seoul, KR), Park; Kyu Sung (Kwangyeok-si, KR) Assignee(s): Korea Advanced Institute of Science &Technology (Kwangyeok-Si, KR) Patent Number: 6,576,216 Date filed: January 9, 2001 Abstract: A method for manufacturing lithium-manganese oxide powders for use in a lithium secondary battery is provided. The method includes the steps of dissolving in nitric acid a composition selected from the group consisting of: manganese oxide, manganese carbonate, or manganese to form a manganese solution, and then dissolving in the manganese solution a composition selected from the group consisting of lithium carbonate, lithium hydroxide, or lithium acetate. Glycine is added to the mixed metal solution and the mixed metal solution is dried in a vacuum dryer to form a combustible resin. The combustible resin is then ignited at room temperature and the combusted products are calcinated. Excerpt(s): The present invention relates to a method for manufacturing lithiummanganese (Li--Mn) oxides which are used for a positive electrode material of Li secondary battery, and more particularly, to a method for manufacturing Li--Mn oxide powders, in which a battery having a high productivity, a large capacity, and a long life cycle is obtained, since powders having an excellent crystallization can be produced by heat-treating for a considerably shorter time than those of conventional methods. In general, there are two technical matters to be solved in relation to a capacity and a lifetime of a Li secondary battery. Firstly, a state transition phenomenon occurring in the process of charging and discharging a battery may reduce a capacity and lifetime of the Li secondary battery. In the case that a Li secondary battery is charged, lithium (Li) existing in Li.sub.x Mn.sub.2 O.sub.4 (x=1) powders being a positive electrode material is extracted and dissolved in an electrolyte, and the dissolved lithium ions are moved to carbon or graphite being a negative electrode. Meanwhile, in the case that the Li secondary battery is discharged, lithium is separated from carbon and inserted into a crystalline lattice of the LiMn.sub.2 O.sub.4 powders again. Here, in the case that x>0.5 in Li.sub.x Mn.sub.2 O.sub.4, lithium exists as a single phase in which a lithium content is successively varied, so that a crystalline structure is continuously varied at the process of inserting and extracting lithium. However, in the case that x<0.5 in Li.sub.x Mn.sub.2 O.sub.4, a lithium content is separated into two different states, that is,.lambda.MnO.sub.2 (x=0) and Li.sub.0.5 Mn.sub.2 O.sub.4 (x=0.5). As a result, the lithium insertion and extraction process accompanies a state transition of.lambda.-MnO.sub.2 and Li.sub.0.5 Mn.sub.2 O.sub.4, to thereby cause the crystalline structure to be severely varied. In this process, since a part of structure in the lattice of the LiMn.sub.2 O.sub.4 powders is destroyed at the time of insertion and extraction of lithium, or Mn.sup.+3 ions are dissolved into the electrolyte, a lifetime of the positive electrode is lowered. Web site: http://www.delphion.com/details?pn=US06576216__
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Methods for treatment of male erectile dysfunction Inventor(s): Podolski; Joseph S. (The Woodlands, TX) Assignee(s): Zonagen, Inc. (The Woodlands, TX) Patent Number: 6,696,072 Date filed: January 31, 2000 Abstract: Improved drug compositions and methods useful in the treatment of male erectile dysfunction. An optimized mixture of the drugs phentolamine mesylate, papaverine hydrochloride, and alprostadil in a buffer containing L-arginine and glycine is to be injected into the penile tissue to produce an erection in otherwise impotent men. Excerpt(s): This invention relates to improved drug compositions useful in the treatment of male erectile dysfunction and also to methods of treatment. More particularly, this invention discloses specific formulations containing the pharmacological agents phentolamine mesylate, papaverine hydrochloride, and alprostadil (prostaglandin E1) in a novel buffer and the administration of such formulations to mammals (including humans) to treat male impotence. Impotence is a common medical disorder affecting about 20 million men in the U.S. alone. Male erectile dysfunction has been defined as the inability to achieve or maintain an erection sufficient for intercourse (Impotence, National Institutes of Health Consensus Development Panel on Impotence Conference, JAMA 1993, 270, 83-90). The dominant etiology for this condition is arterial insufficiency associated with cardiovascular disease. Male erectile dysfunction adversely impacts the quality of life, being frequently associated With depression, anxiety, and low selfesteem. Although male erectile dysfunction represents a major clinical problem, treatment for this condition remains problematic and unsatisfactory. One of the least invasive therapies available entails the use of a vacuum constriction device on the penis to produce an erection. The physiology of the penis is such that blood flows in through arteries deep within the tissue while blood flows out through veins near the skin surface. By placing a plastic cylinder over the shaft of the penis and employing a vacuum pump to restrict venous blood flow from the penis, the corpus cavernosum penile tissue becomes engorged with trapped blood and an erection is produced. Common patient complaints are that this device is interruptive to the sex act, has a short duration of effectiveness, and can cause tissue damage to the penis, such as necrosis, with extended use. Web site: http://www.delphion.com/details?pn=US06696072__
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Morphan derivatives or salts thereof and medicinal compositions containing the same Inventor(s): Fukushima; Hidenao (Ibaraki, JP), Kibayashi; Chihiro (Tokyo, JP), Miyata; Takeshi (Kumamoto, JP), Takahama; Kazuo (Kumamoto, JP) Assignee(s): Hisamitsu Pharmaceutical Co., Ltd. (Saga, JP) Patent Number: 6,608,080 Date filed: August 16, 2001 Abstract: Medicinal compositions having an effect of regulating the activation of glycine receptor and novel morphan derivatives. Medicinal compositions comprising morphan derivatives or its salts and a pharmaceutically acceptable carrier. These compositions potentiate or inhibit the activation of glycine receptor, which makes them useful as
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drugs for the central nervous system. Novel 1- and/or 2-substituted morphan derivatives (2-azabicyclo[3.3.1]nonane derivatives) or salts thereof. Excerpt(s): The present invention relates to regulators for the activation of glycine receptors comprising morphan derivatives or salts thereof. The described regulators potentiate or inhibit the activation of the receptor (glycine receptors) which is specifically bound with the inhibitory neurotransmitter glycine. More particularly, the potentiators for the activation of glycine described in the present invention are useful as drugs for the treatment of convulsive seizures or epileptic seizures and as anesthetics. Further, the inhibitors for the activation of glycine receptors described in the present invention are useful as drugs for the treatment of nonketotic hyperglycinemia, and as antitussives or central nervous system stimulants. The regulators for the activation of glycine receptors described in the present invention are also useful as pharmacological tools for analyzing the function of these receptors. The present invention also relates further to the medicinal compositions containing morphan derivatives represented by the formula (1) or salts thereof and pharmaceutically acceptable carrier thereof. Further, the present invention relates to novel compounds comprising morphan derivatives or salts thereof represented by the formula (2). Glycine is a major inhibitory neurotransmitter of the central nervous system and is distributed mainly in the medulla and the spinal cord. This is in sharp contrast to another inhibitory neurotransmitter,.UPSILON.-aminobutyric acid (GABA), which is distributed in the upper central region. With regard to the GABA receptor and the GABAergic neurotransmitter mechanism, a binding site, which is modified by antianxiety drugs, anesthetics, anticonvulsants or hypnotics, acting on the GABA receptor-ionchannel complex (hereinafter designated as the GABA receptor) has been elucidated (Ann. Rev. Neurosci., 17, 569-602, 1994); and drugs targeting the GABA receptor have been developed extensively. The importance of the GABA receptor for maintaining the functions of the psychoneural system has been recognized, and its physiological roles and pharmacological significance, including its regulatory mechanism, have been thoroughly elucidated. On the contrary, with regard to drugs modifying the functions of the glycine receptors, such as the known glycine receptors antagonist, strychnine, only a small number of drugs has been found. Owing to this fact, the pharmacological significance of glycine receptors has not been well elucidated and even their physiological role remains unknown. Web site: http://www.delphion.com/details?pn=US06608080__ •
Nutritional or therapeutic compositions Inventor(s): Crum; Albert (77 Remsen St., Brooklyn Heights, NY 11201) Assignee(s): none reported Patent Number: 6,592,908 Date filed: September 23, 2002 Abstract: Nutritional or therapeutic compositions containing glutamic acid, cystine, glycine and a selenium precursor and methods for their utilization to increase glutathione synthesis and thereby enhance the immune system are described. Excerpt(s): This invention relates to nutritional or therapeutic compositions useful for treating mammals to increase their body content of glutathione above a pretreatment level thereby to enhance the immune activity of the treated mammal. More specifically, it relates to compositions containing a selenium compound together with a glutathione
Patents 147
precursor which is a mixture of glutamic acid, cystine and glycine. Its chemical name is glutamyl-cysteinyl-glycine. Like many other small peptides in the mammalian body, it is not synthesized by procedures involving DNA, RNA and ribosomes. Rather, it is synthesized from the amino acids available in the body by procedures utilizing enzymes and other body components such as adenosine triphosphate as an energy source. Web site: http://www.delphion.com/details?pn=US06592908__ •
Pap mutants that exhibit anti-viral and/or anti-fungal activity in plants Inventor(s): Tumer; Nilgun E. (Belle Mead, NJ) Assignee(s): Rutgers, The State University (New Brunswick, NJ) Patent Number: 6,627,736 Date filed: August 15, 2000 Abstract: Disclosed are PAP mutants having reduced phytotoxicity compared to wildtype PAP, and which confer broad spectrum resistance to viruses and/or fungi in plants. One group of PAP mutants is characterized by at least one amino acid substitution in the N-terminus of mature PAP, such as the Glycine 75 residue or the Glutamic acid 97 residue; two groups of additional PAP mutants are characterized by truncations in the N-terminal region of mature PAP and truncations or amino acid substitutions in the C-terminal region of mature PAP, respectively; and a further group are enzymatically inactive which still exhibit anti-fungal properties. Also disclosed are DNA molecules encoding the PAP mutants, mutant PAP DNA constructs, and transgenic seed and plants containing the DNAs. Further disclosed are methods for identifying PAP mutants having reduced phytotoxicity, as well as isolated and purified PAP mutants identified by the method. Excerpt(s): This invention relates generally to agricultural biotechnology, and more specifically to methods and genetic materials for conferring resistance to fungi and/or viruses in plants. The subject of plant protection against pathogens remains the area of utmost importance in agriculture. Many commercially valuable agricultural crops are prone to infection by plant viruses and fungi capable of inflicting significant damage to a crop in a given season, and drastically reducing its economic value. The reduction in economic value to the farmer in turn results in a higher cost of goods to ultimate purchasers. Several published studies have been directed to the expression of plant virus capsid proteins in a plant in an effort to confer resistance to viruses. See, e.g., Abel et al., Science 232:738-743 (1986); Cuozzo et al., Bio/Technology 6:549-557 (1988); Hemenway et al., EMBO J. 7:1273-1280 (1988); Stark et al., Bio/Technology 7:1257-1262 (1989); and Lawson et al., Bio/Technology 8:127-134 (1990). However, the transgenic plants exhibited resistance only to the homologous virus and related viruses, but not to unrelated viruses. Kawchuk et al., Mol. Plant-Microbe Interactions 3(5):301-307 (1990), disclose the expression of wild-type potato leaf roll virus (PLRV) coat protein gene in potato plants. Even though the infected plants exhibited resistance to PLRV, all of the transgenic plants that were inoculated with PLRV became infected with the virus and thus disadvantageously allowed for the continued transmission of the virus such that high levels of resistance could not be expected. See U.S. Pat. No. 5,304,730. Lodge et al., Proc. Natl. Acad. Sci. USA 90:7089-7093 (1993), report the Agrobacterium tumefaciensmediated transformation of tobacco with a cDNA encoding wild-type pokeweed antiviral protein (PAP) and the resistance of the transgenic tobacco plants to unrelated viruses. PAP, a Type I ribosome-inhibiting protein (RIP) found in the cell walls of Phytolacca americana (pokeweed), is a single polypeptide chain that catalytically
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removes a specific adenine residue from a highly conserved stem-loop structure in the 28S rRNA of eukaryotic ribosomes, and interferes with elongation factor-2 binding and blocking cellular protein synthesis. See, e.g., Irvin et al., Pharmac. Ther. 55:279-302 (1992); Endo et al., Biophys. Res. Comm., 150:1032-36 (1988); and Hartley et al., FEBS Lett. 290:65-68 (1991). The observations by Lodge were in sharp contrast to previous studies, supra, which reported that transgenic plants expressing a viral gene were resistant to that virus and closely related viruses only. See also Beachy et al., Ann. Rev. Phytopathol. 28:451-74 (1990); and Golemboski et al., Proc. Natl. Acad. Sci. USA 87:631115 (1990). Lodge also reports, however, that the PAP-expressing tobacco plants (i.e., above 10 ng/mg protein) tended to have a stunted, mottled phenotype, and that other transgenic tobacco plants that accumulated the highest levels of PAP were sterile. RIPs have proven unpredictable in other respects such as target specificity. Unlike PAP which (as demonstrated in Lodge), ricin isolated from castor bean seed is 1000 times more active on mammalian ribosomes than plant ribosomes. See, e.g., Harley et al., Proc. Natl. Acad. Sci. USA 79:5935-5938 (1982). Barley endosperm RIP also shows very little activity against plant ribosomes. See, e.g., Endo et al., Biochem. Biophys. Acta 994:224226 (1988) and Taylor et al., Plant J. 5:827-835 (1984). Web site: http://www.delphion.com/details?pn=US06627736__ •
Pharmaceutical combinations for the treatment of stroke and traumatic brain injury Inventor(s): Chenard; Bertrand L. (Waterford, CT), Menniti; Frank S. (Mystic, CT), Saltarelli; Mario D. (Mystic, CT) Assignee(s): Pfizer Inc (New York, NY) Patent Number: 6,667,317 Date filed: September 6, 2001 Abstract: This invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); or (i) an antiinflammatory agent. Excerpt(s): This invention relates to methods of treating traumatic brain injury (TBI), ischemic stroke, or hypoxic brain injury, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with one or more other compounds that protect neurons from toxic insult, inhibit the inflammatory reaction after brain damage or promote cerebral reperfusion. More specifically, this invention relates to methods of treating traumatic brain injury (TBI) or hypoxic or ischemic stroke, comprising administering to a patient in need of such treatment an NR2B subtype selective N-methyl-D-aspartate (NMDA) receptor antagonist in combination with either: (a) a neutrophil inhibitory factor (NIF); (b) a sodium channel antagonist; (c) a nitric oxide synthase (NOS) inhibitor; (d) a glycine site antagonist; (e) a potassium channel opener; (f) an AMPA/kainate receptor antagonist; (g) a calcium channel antagonist; (h) a GABA-A receptor modulator (e.g., a GABA-A receptor agonist); (i) an antiinflammatory agent; or (j) a matrix metalloprotease (MMP) inhibitor. Brain and spinal cord injury caused by stroke, trauma or hypoxia often result in lifelong disability and premature death. The cause of disability and death is the
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disruption of function and frank death of neurons and other cells in the central nervous system. Therefore, a clear benefit is anticipated from therapies that reduce or prevent neuronal dysfunction and death after ischemic, hypoxic or traumatic CNS insult. Web site: http://www.delphion.com/details?pn=US06667317__ •
Polyacrylamide precast gels for electrophoresis, process for producing the same and electroporesis method by using the gels Inventor(s): Suzuki; Mika (Tokyo, JP) Assignee(s): Hymo Corporation (Tokyo, JP) Patent Number: 6,726,821 Date filed: August 2, 2001 Abstract: A precast acrylamide electrophoresis gel is disclosed, which includes a gel buffer solution containing either Tris and glycine or Tris, glycine and any one or more than two of ampholytes, and a monobasic acid, titrated to a specified pH range. With the gels constituted as stated earlier, proteins can be successfully subjected to electrophoresis using the commonly available Laemmli's buffer system, while the DNA can be also satisfactorily run on the gel using the electrophoresis electrode solution containing Tris, chelating agent, and any one acid of acetic acid, phosphoric acid and boric acid. In either of protein and DNA analyses, the gels even after stored under refrigeration more than six months are fully comparable in resolution and clearness of electrophoretic pattern to the gels just after being prepared. Where the DAN is subjected to electrophoresis using either the Laemmli's buffer or the Ornstein and Davis buffer, commonly used in electrophoresis of proteins, the gels even after storage under refrigeration over four months may exhibit the electrophoretic patterns comparable in resolution and clearness to the gels soon after being produced. Excerpt(s): The present application is the national stage under 35, U.S.C. 371, of international application PCT/JP00/08465, filed Nov. 30, 2000, which designated the United States, and which international application was not published under PCT Article 21(2) in the English language. The present invention relates to a precast polyacrylamide gel adapted for use in electrophoresis separation, production method thereof and electrophoresis using the gel. Precast polyacrylamide gels for electrophoresis are extensively used as a basic investigative medium for detecting and quantitatively analyzing chemical substances: proteins, nucleic acids, carbohydrates, and lipids necessary for building all living organisms in fields as diverse as biology, medicine, fisheries, veterinary medicine, and so on. Especially, a variety of precast polyacrylamide gels different in resolving power can be made easily by varying a gel recipe because the gels are substances synthesized artificially. Accordingly, it is possible to prepare in advance the precast gels differing diversely in separation characteristic or resolution from one another. The artificial gels, since much saving the labor and effort for analytic procedure and excellent in uniformity and reproducibility, have helped the productivity and quality control in the fields stated earlier. The artificial gels which are massproduced must have an increased shelf-life to ensure an adequate supply of these gels. Web site: http://www.delphion.com/details?pn=US06726821__
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Preparing monomeric metal ion chelator containing diacetyl glycine group linked to proteinaceous molecule Inventor(s): Savage; M. Dean (Rockford, IL), Sykaluk; Laura L. (Rockford, IL) Assignee(s): Pierce Biotechnology, Inc. (Rockford, IL) Patent Number: 6,670,159 Date filed: July 25, 2001 Abstract: A precursor for the construction of chelated metal conjugates which demonstrate improved assay performance and utility in minimizing non-specific binding while maintaining specificity for target molecules is disclosed. The precursor has tridentate functionality towards multivalent ions such as iron and nickel and contains a diacetyl glycine group covalently linked via an amide to a molecule such as a proteinaceous molecule providing a primary amide group for amide bond formation. The precursor is preferably prepared in monomeric form by reacting nitrilotriacetic acid or a salt thereof in an aqueous medium at an alkaline pH of at least 8 with a proteinaceous molecule containing a primary amine group in the presence of a carbodiimide. The proteinaceous molecule may be bovine serum albumin or an enzyme such as alkaline phosphatase or horseradish peroxidase. Excerpt(s): The present inventions relates to metal ion affinity interactions with target molecules and, more particularly, to improvements thereof whereby non-specific interactions with non-target molecules can be diminished. Affinity binding interaction based on the used of a chelated metal have been widely used due to the propensity of certain metals to preferably bind to given functional groups on target molecules such as proteins, peptides, and like compounds. Immobilized metal-ion chromatography, for example, has been used with a variety of different metals. Phosphorylated target molecules have been purified using columns containing immobilized ferric ions. Polyhistidine tagged fusion proteins nave been purified using columns containing immobilized divalent nickel. Peroxidase and biotin probes containing chelated metals have also been used for polyhistidine tagged fusion protein detection and in connection with immunoassays. It is recognized that in metal-ion chromatography, the chelating functionality used to immobilize the metal to construct the chelator-metal conjugate is important. With iron, iminodiacetic acid functionality has been used due to its tight binding characteristics with ferric ions. With nickel, as well with many other less used metal ions, the nitrilotriacetic acid tetradentate functionality has been used in both column and probe formats due to its tight binding characteristics with these metal ions. Web site: http://www.delphion.com/details?pn=US06670159__
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Process for the preparation of derivatives of 4-amino-3-hydroxypyrrole-2-carboxylic acid Inventor(s): Phillion; Dennis P. (St. Louis, MO), Singh; Megh (Bridgeton, MO) Assignee(s): Pharmacia Corporation (Chicago, IL) Patent Number: 6,632,950 Date filed: July 5, 2001 Abstract: Novel processes and intermediates are provided for the synthesis of derivatives of 4-amino-3-hydroxypyrrole-2-carboxylic acids that are useful as monomers for polyamides capable of binding dsDNA. According to one preferred reaction scheme,
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an alkyl alkoxymethylene nitroacetate (Formula VIII) is prepared by reaction of a trialkyl orthoformate or orthoacetate with a nitroacetate ester in the presence of a carboxylic anhydride. The compound of Formula VIII is condensed with an Nsubstituted glycine to yield an N-substituted (2-nitro-2-alkoxycarbonyl)vinyl glycinate ester (Formula VII). Ring closure in the presence of an alkali metal alkoxide yields a 4nitro-3-hydroxypyrrole-2-carboxylic ester (Formula V). After blocking of the 3-hydroxy group to produce a further intermediate (Formula IV), the 4-nitro group is reduced to a 4-amino group (Formula III), and the 4-amino group is then blocked by reaction with a dicarbonate diester to produce the fully blocked intermediate (Formula II). Saponification of the 2-carboxylic acid ester yields a monomer having a free 2-carboxylic ester moiety (Formula I). Excerpt(s): This invention relates the preparation of compounds useful as monomers in the preparation of polyamides, and more particularly to novel methods and novel intermediates for the preparation of 3-hydroxypyrrole monomers for polyamides that are useful in nucleotide sequence recognition. Certain polyamides derived from heteroaryl amino acid monomers are capable of binding to dsDNA and have been found useful in the recognition of nucleotide sequences as well as other applications. See, for example, Dervan U.S. Pat. No. 5,998,140 and Urbach et al., "Sequence Selectivity of 3Hyroxypyrrole/Pyrrole Ring Pairings in the DNA Minor Groove," J. Am. Chem. Soc., 1999, 121, 11621-11629. Polyamides containing various combinations of amino acid units respectively comprising pyrrole, hydroxypyrrole and imidazole moieties have been found particularly suitable for this purpose. G/C base pairs have been found to be complemented by the juxtaposed combination of N-methylimidazole/N-methylpyrrole, C/G pairs by N-methylpyrrole/N-methylimdazole, and T/A pairs by Nmethylpyrrole/N-methylpyrrole or N-methyl-3-hydroxypyrrole/N-methylpyrrole. Polyamides containing these combinations can form intracellular complexes by complementation with sequences in dsDNA, the complementation being advantageously facilitated by providing a hairpin turn in the polyamide, or may be accomplished by using two amide oligomers. Methods for the preparation of hairpin polyamide polymers and monomers useful in their synthesis are described in the abovecited Dervan patent and Urbach et al. article. An earlier article of Momose et al., "3Hydroxypyrrole. I. A General Synthetic Route to 4,5-Unsubstituted Alkyl 3Hydroxypyrrole-2-carboxylates," Chem. Pharm. Bull., 26(7), 2224-2238 (1979) also describes methods for the preparation of amino acids derivatives of 3-hydroxypyrrole. Web site: http://www.delphion.com/details?pn=US06632950__ •
Process for the preparation of glycine derivatives and use thereof Inventor(s): Thurmuller; Oliver (Dusseldorf, DE), Tomuschat; Phillipp (Essen, DE) Assignee(s): Goldschmidt AG (Essen, DE) Patent Number: 6,663,764 Date filed: April 4, 2002 Abstract: Process for the preparation of glycine derivatives, which comprises electrochemically oxidizing.beta.-hydroxyethylammonium compounds to give the corresponding acids. Excerpt(s): The present invention relates to glycine derivatives, and more particularly to a process for preparing glycine derivatives that are free from organically bonded halogen and/or halide ions. The present invention also relates to the use of such glycine
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derivatives in cosmetic preparations. Glycine derivatives such as betaines are known as mild and compatible substances which may be typically co-used in large amounts for the preparation of cosmetic preparations for the cleansing and care of skin and hair. In the prior art, glycine derivatives are typically prepared by reacting tertiary amines with excess monochloroacetic acid in a basic aqueous solution at an elevated temperature. Web site: http://www.delphion.com/details?pn=US06663764__ •
Stabilized interleukin 2 Inventor(s): Nayar; Rajiv (Richmond, CA), Shearer; Michael A. (Fairfield, CA), Wang; Wei (Alameda, CA) Assignee(s): Bayer Pharmaceuticals Corporation (West Haven, CT) Patent Number: 6,689,353 Date filed: June 28, 2000 Abstract: A stable pharmaceutical preparation comprising Human interleukin-2 or a variant thereof and a stabilizing amount of histidine. A preferred formulation includes glycine and sucrose and a variant of IL-2 having a single mutation, N88R. The preferred formulation is in lyophilized form which, on reconstitution with an aqueous diluent, results in a solution having a pH ranging from about 5.0 to 6.5. Excerpt(s): The invention is generally related to the field of pharmaceutical formulations. More specifically, the invention is directed to a stabilized, therapeutically active Interleukin-2 formulation capable of selectively activating T cells (PHA-blasts) and, very preferably, including an IL-2 mutein demonstrating reduced activation of Natural Killer ("NK") cells. The stabilized compositions having the preferred properties include variants of IL-2 described below. As discussed in a related application PCT/US 99/10643 published Nov. 25, 1999, Interleukin 2 (IL-2) is a potent immune stimulator, activating diverse cells of the immune system, including T cells, B cells, and monocytes. IL-2 is also a potent and critical growth factor of T cells. It was by virtue of these activities that IL-2 was tested for its ability to treat cancer. Human IL-2 is a FDA approved drug for the treatment of metastatic renal carcinoma and metastatic melanoma. The use of IL-2 in eligible patients is restricted due to the severe toxicity associated with IL-2 therapy; it is estimated that at best only 20% of eligible patients actually receive therapy. The toxicities associated with IL-2 therapy include severe fever, nausea, vomiting, vascular leak and serious hypotension. Despite these toxicities, however, IL-2 is effective for its approved indications. Variants of IL-2 having reduced toxicity are the subject matter of application WO 99/60128. Significant information on stabilization of IL-2 and other therapeutic protein formulations is available. The currently approved Human IL-2 preparation (Proleukin.RTM. IL-2, Chiron Corporation) is a freeze-dried preparation which includes mannitol, sodium dodecyl sulfate (SDS) and a phosphate buffer. Other formulated therapeutic proteins, including IL-2, are described in the following references. Fernandes et al., 1986, Pharmaceutical compositions of microbially produced interleukin-2 (U.S. Pat. No. 4,604,377) describes a freeze-dried formulation containing a stabilizer (mannitol) and a solubilizing agent such as sodium dodecyl sulfate or sodium deoxycholate sulfate at about 100 to about 250 ug per mg of IL-2. The formulation for the currently available Proleukin.RTM. IL-2 product is believed to be described in this reference. Web site: http://www.delphion.com/details?pn=US06689353__
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Stabilized protein preparation and process for its preparation Inventor(s): Roemisch; Juergen (Marburg, DE), Stauss; Harald (Dautphetal, DE), Stoehr; Hans-Arnold (Wetter, DE) Assignee(s): Aventis Behring GmbH (Marburg, DE) Patent Number: 6,737,405 Date filed: May 7, 2001 Abstract: A stabilized protein preparation is described which contains no antithrombin III and is protected against loss of activity during pasteurization by the addition of stabilizers which comprise one or more saccharides as a mixture with more than 0.5 mol/l of one or more amino acids chosen from the group arginine, lysine, histidine, phenylalanine, tryptophan, tyrosine, aspartic acid and its salts or glutamic acid and its salts. Glycine and/or glutamine can also be additionally added to each of these amino acids. A process for the viral inactivation or viral depletion of a protein preparation of this type which contains the abovementioned stabilizers and is subjected to pasteurization or viral depletion by filtration, centrifugation or treatment with detergents or bactericidal or virucidal agents is also described. Excerpt(s): The invention relates to a stabilized protein preparation which contains therapeutically active proteins and is protected against a loss of action or the denaturation of the proteins during pasteurization by the addition of stabilizers. Moreover, processes for viral inactivation and viral depletion of the protein preparations stabilized according to the invention are described. These include, inter alia, nanofiltration and treatment with bactericidal or virucidal substances or detergents. It is known that certain proteins are employed in the form of concentrates for the prophylaxis and therapy of different diseases which are caused by hereditary or acquired deficiency states of these proteins. Blood plasma or organ extracts particularly serve here as a source of the therapeutically administered proteins. Recently, appropriate proteins prepared recombinantly or transgenically have also been therapeutically administered. Each of the sources mentioned involves, however, the potential risk of an introduction of infectious organisms such as bacteria, viruses and prions. Therefore, numerous processes have also already been developed which can counteract such a potential contamination of protein preparations. With pasteurization, in particular the heating of protein solutions at 60.degree. C. for a period of 10 hours, a very effective process for the inactivation of infectious viruses and other pathogens is already available which has decisively improved the safety standard with respect to the transmission of infections by protein preparations. In addition, further procedures have been developed such as the treatment of the preparations with detergents or bactericidal or virucidal agents. Moreover, mechanical separation of organisms, for example, by means of a suitable filtration such as "nanofiltration", can also be carried out. Web site: http://www.delphion.com/details?pn=US06737405__
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Therapeutic quassinoid preparations with antineoplastic, antiviral, and herbistatic activity Inventor(s): Corbett; Thomas H. (Gross Pointe Park, MI), Grieco; Paul A. (Gosport, IN), Morre; D. James (West Lafayette, IN), Valeriote; Frederick A. (Utica, MI) Assignee(s): Advanced Research and Technology Institute, Inc. (Indianapolis, IN) Patent Number: 6,573,296 Date filed: April 16, 1999 Abstract: The present invention includes purified and isolated quassinoids and synthetically derived quassinoid analogs based on a picrasane carbon skeleton. Novel sidechains at C-15 incorporating water solubilizing agents such as glycine are discussed. Therapeutic methods taking advantage of anticancer, antiviral, and herbistatic properties of these quassinoids are disclosed, including use against solid tumors and human immunodeficiency virus infected cells. Excerpt(s): The botanical family Simaroubaceae includes numerous species distributed primarily in pantropical regions. These plant species have been the source of a large family of bitter terpenold substances collectively termed quassinoids. Like many plant alkaloids or naturally isolated plant extracts, quassinoids have been found to have diverse biologic activity, including anti-malarial, anti-insecticidal, anti-amoebicidal, anti-leukemic, and anti-viral activity. wherein R.sub.1 represents hydrogen, oxygen, alkyl, alkenyl, acyl, aryl, halogen, sulfo, nitro, carboxyl, hydroxyl, hydroxyalkyl, alkoxy, or other water soluble sidechain, and Y is a sidechain comprising hydrogen, alkyl, hydroxyalkyl, carboxyl, aryl, alkenyl, cycloalkanes, cycloalkenes, glycosaccharides, water soluble sidechains, amino acid, peptide, and any of the foregoing attached at C-15 by an ether, ester, carbonyl, or glycosidic linkage. wherein R.sub.2, R.sub.3, and R.sub.4 taken separately or together represent hydrogen, alkyl, hydroxyalkyl, carboxyl, aryl, alkenyl, cycloalkanes, cycloalkenes, glycine, glycosaccharides, water soluble sidechains, amino acids, peptide, and any of the foregoing attached to the central carbon by an ether, ester, carbonyl, or glycosidic linkage. Web site: http://www.delphion.com/details?pn=US06573296__
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Use of a supplemental promoter in conjunction with a carbon-supported, noble-metal containing catalyst in liquid phase oxidation reactions Inventor(s): Ebner; Jerry R. (St. Peters, MO), Leiber; Mark A. (St. Peters, MO), Rogers; Peter (Des Peres, MO), Wan; Kam-To (Manchester, MO), Woods; Anthony (Ossett, GB) Assignee(s): Monsanto Technology LLC (St. Louis, MO) Patent Number: 6,586,621 Date filed: December 21, 2000 Abstract: This invention relates to the use of a supplemental promoter in conjunction with a noble-metal-containing catalyst comprising a carbon support in catalyzing liquid phase oxidation reactions, a process for making of an improved catalyst comprising such a supplemental promoter, and an improved catalyst comprising such a supplemental promoter.In a particularly preferred embodiment, a supplemental promoter (most preferably bismuth or tellurium) is used in conjunction with a noblemetal-containing catalyst comprising a carbon support in a liquid phase oxidation process wherein N-(phosphonomethyl) iminodiacetic acid (i.e., "PMIDA") or a salt
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thereof is oxidized to form N-(phosphonomethyl) glycine (i.e., "glyphosate") or a salt thereof. The benefits of such a process include increased oxidation of the formaldehyde and formic acid by-products, and, consequently, decreased final concentrations of those by-products as well as other undesirable by-products, most notably N-methyl-N(phosphonomethyl) glycine (i.e., "NMG"). Excerpt(s): This invention generally relates to liquid phase oxidation processes using a carbon-supported, noble-metal-containing catalyst (particularly a deeply reduced catalyst) in conjunction with a supplemental promoter (e.g., bismuth or tellurium). In an especially preferred embodiment, this invention relates to such a process wherein N(phosphonomethyl)iminodiacetic acid ("PMIDA") or a salt thereof is oxidized to form N(phosphonomethyl)glycine (also known in the agricultural chemical industry as "glyphosate") or a salt thereof. This invention also generally relates to enhancing the activity, selectivity, and/or stability of a carbon-supported, noble-metal-containing catalyst (particularly a deeply reduced catalyst) using a supplemental promoter. N(phosphonomethyl)glycine is described in Franz, U.S. Pat. No. 3,799,758. N(phosphonomethyl)glycine and its salts are conveniently applied as a post-emergent herbicide in an aqueous formulation. Glyphosate is a highly effective and commercially important broad-spectrum herbicide useful in killing or controlling the growth of a wide variety of plants, including germinating seeds, emerging seedlings, maturing and established woody and herbaceous vegetation, and aquatic plants. Other by-products also typically form, such as formic acid (HCO.sub.2 H), which is formed by the oxidation of the formaldehyde by-product; and aminomethylphosphonic acid ("AMPA"), which is formed by the oxidation of N-(phosphonomethyl)glycine. Even though the Franz method produces an acceptable yield and purity of N(phosphonomethyl)glycine, high losses of the costly noble metal into the reaction solution (i.e., "leaching") result because, under the oxidation conditions of the reaction, some of the noble metal is oxidized into a more soluble form, and both PMIDA and N(phosphonomethyl)glycine act as ligands which solubilize the noble metal. Web site: http://www.delphion.com/details?pn=US06586621__
Patent Applications on Glycine As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to glycine: •
Arylglycine derivatives for use as glycine transport inhibitors Inventor(s): Arora, Jalaj; (Milton, CA), Da Silva-Turcot, Kathleen; (Toronto, CA), Isaac, Methvin; (Etobicoke, CA), Maddaford, Shawn; (Mississauga, CA), O'Brien, Anne; (Toronto, CA), Slassi, Abdelmalik; (Mississauga, CA), Stefanac, Tomislav; (Burlington, CA), Xin, Tao; (Woodbridge, CA) Correspondence: John W. Ryan; C/o Dechert Llp; Princeton Pike Corporation Center; P.O. Box 5218; Princeton; NJ; 08543-5218; US Patent Application Number: 20040152740 Date filed: September 8, 2003
9
This has been a common practice outside the United States prior to December 2000.
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Abstract: The present invention relates to compounds of Formula 1: 1and salts solvates and hydrates thereof. The invention further relates to pharmaceutical compositions containing said compounds and methods of treating neurological and neuropsychistric disorders using said compounds. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/409,420 filed Sep. 9, 2002. The present invention relates to a class of compounds, to pharmaceutical compositions containing them and to methods of treating neurological and neuropsychiatric disorders using such compounds. Synaptic transmission is a complex form of intercellular communication that involves a considerable array of specialized structures in both the pre- and post-synaptic terminal and surrounding glial cells (Kanner and Schuldiner, CRC Critical Reviews in Biochemistry, 22, 1987:1032). Transporters sequester neurotransmitters from the synapse, thereby regulating the concentration of neurotransmitters in the synapse, and their duration therein, which together influence the magnitude of synaptic transmission. Further, by preventing the spread of neurotransmitters to neighbouring synapses, transporters maintain the fidelity of synaptic transmission. Lastly, by sequestering released neurotransmitter into the presynaptic terminal, transporters allow for neurotransmitter re-utilization. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Central airway administration for systemic delivery of therapeutics Inventor(s): Bitonti, Alan J.; (Acton, MA), Blumberg, Richard S.; (Chestnut Hill, MA), Lencer, Wayne I.; (Jamaica Plain, MA), Simister, Neil E.; (Wellesley, MA) Correspondence: Alan W. Steele; Wolf, Greenfield & Sacks, P.C.; 600 Atlantic Avenue; Boston; MA; 02210; US Patent Application Number: 20040063912 Date filed: July 17, 2003 Abstract: The present invention relates to methods and products for the transepithelial systemic delivery of therapeutics. In particular, the invention relates to methods and compositions for the systemic delivery of therapeutics by administering an aerosol containing antibodies or conjugates of a therapeutic agent with an FcRn binding partner to epithelium of central airways of the lung. The methods and products are adaptable to a wide range of therapeutic agents, including proteins and polypeptides, nucleic acids, drugs, and others. In particular embodiments the conjugates are fusion proteins in which a therapeutic polypeptide is joined at its C terminal end through a peptide linker to the N terminal end of an immunoglobulin Fc gamma heavy chain, wherein the linker includes Glycine and Serine residues and is preferably 15 amino acids long. In one embodiment the fusion protein includes an interferon-alpha 2b (IFN-.alpha.2b) joined at its C terminal end through a peptide linker having a sequence Gly-Gly-Gly-Gly-Ser-GlyGly-Gly-Gly-Ser-Gly-Gly-Gly-Gly- -Ser (SEQ ID NO:29) to the N terminal end of a human Fc.gamma.1 heavy chain. The methods and products have the advantage of not requiring administration to the deep lung in order to effect systemic delivery. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 10/435,608, filed May 9, 2003, now pending, which is a continuation-in-part of international patent application PCT/US02/21355, filed Jul. 3, 2002, designating the United States and now pending, which in turn claims benefit of U.S. provisional patent application U.S. patent application serial No. 60/364,482, filed Mar. 15, 2002, now expired. The present invention relates to methods and products for the transepithelial
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systemic delivery of therapeutics. In particular, the invention relates to methods and compositions for the systemic delivery of therapeutics which include a neonatal Fc receptor (FcRn) binding partner by their administration to central airways of the lung. Such therapeutics include therapeutic and diagnostic IgG antibodies as well as conjugates formed between a therapeutic agent and an FcRn binding partner. The methods and compositions are useful for any indication for which the therapeutic is itself useful in the detection, treatment or prevention of a disease, disorder, or other condition of a subject. Transport of macromolecules across an epithelial barrier can occur by receptor-nonspecific or receptor-specific mechanisms. Receptor-nonspecific mechanisms are represented by paracellular sieving events, the efficiency of which are inversely related to the molecular weight of the transported molecule. Transport of macromolecules such as immunoglobulin G (IgG) via this paracellular pathway is highly inefficient due to the large molecular mass of IgG (ca. 150 kDa). Receptornonspecific transport may include transcytosis in the fluid phase. This is much less efficient than receptor-mediated transport, because most macromolecules in the fluid phase are sorted to lysosomes for degradation. In contrast, receptor-specific mechanisms which may provide highly efficient transport of molecules otherwise effectively excluded by paracellular sieving. Such receptor-mediated mechanisms may be understood teleologically as effective scavenger mechanisms for anabolically expensive macromolecules such as albumin, transferrin, and immunoglobulin. These and other macromolecules would otherwise be lost at epithelial barriers through their diffusion down an infinite concentration gradient from inside to outside the body. Receptorspecific mechanisms for transport of macromolecules across epithelia exist for only a few macromolecules. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Compositions and methods for preserving personal care products Inventor(s): Anderson, Jamie; (Pleasant Grove, UT), Lewis, Matthew R.; (American Fork, UT), Miser, Daniel A.; (Provo, UT), Wang, Chong; (Draper, UT) Correspondence: Workman Nydegger (f/k/a Workman Nydegger & Seeley); 60 East South Temple; 1000 Eagle Gate Tower; Salt Lake City; UT; 84111; US Patent Application Number: 20040096528 Date filed: June 26, 2003 Abstract: Personal care product preservation systems and methods comprise the use of wasabi and a co-preservative, such as pentylene glycol or a mixture of undecylenoyl glycine and capryloyl glycine to preserve a personal care product. The wasabi provides a natural preservative effect that inhibits the growth of microbes that can otherwise flourish in personal care products. The personal care products can be in the form of emulsions, gels, serums, solutions, and other vehicles suitable for use with personal care products, such as toners, lotions, creams, and the like. Personal care product preservation systems and methods may also comprise the mixture of undecylenoyl glycine and capryloyl glycine to preserve a personal care product. Excerpt(s): This application claims priority under 35 U.S.C.sctn. 119(e) to U.S. provisional application Serial No. 60/391,757, filed Jun. 26, 2002. For purposes of disclosure, the foregoing application is incorporated herein in its entirety. The present invention relates generally to all-natural compositions and methods for preserving personal care products. More particularly, the invention relates to the use of wasabi and it derivatives as a preservative for personal care products. Water-based personal care
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products, such as lotions and toners, provide an hospitable environment for microbial growth. Microbes can be introduced to personal care products, for example, during manufacture, storage, and/or consumer use. How quickly the microbes grow and render the product unsuitable for use is a function of various factors, including the susceptibility of individual products to microbial growth, the presence or absence of preservatives, and the storage condition of the personal care product after the microbial contamination first occurs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Excitatory glycine receptors and methods Inventor(s): Awobuluyi, Marc; (San Francisco, CA), Chatterton, Jon E.; (San Diego, CA), Lipton, Stuart A.; (Rancho Santa Fe, CA), Sevarino, Kevin A.; (Cheshire, CT), Zhang, Dongxian; (San Diego, CA) Correspondence: Campbell & Flores Llp; 4370 LA Jolla Village Drive; 7th Floor; San Diego; CA; 92122; US Patent Application Number: 20040033500 Date filed: August 16, 2002 Abstract: The invention provides isolated N-methyl-D-aspartate type 3B (NR3B) polypeptides, functional fragments and peptides, encoding nucleic acid molecules and polynucleotides, and specific antibodies. Also provided are excitatory glycine receptors, containing either NR3B or NR3A polypeptides. Further provided are methods for detecting excitatory glycine receptor ligands, agonists and antagonists. The invention also provides related diagnostic and therapeutic methods. Excerpt(s): This application is based on, and claims the benefit of, U.S. Provisional Application No. 60/______ (yet to be assigned), filed Aug. 20, 2001, which was converted from U.S. Ser. No. 09/934,070, and which is incorporated herein by reference. This invention relates generally to the fields of neurobiology and medicine and, more specifically, to the field of ionotropic receptors. Ionotropic glutamate receptors activate ligand-gated cation channels that mediate the predominant component of excitatory neurotransmission in the central nervous system (CNS). These receptors have been classified based on their preference for the glutamate-like agonists (RS)-2-amino-3-(3hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA), kainate (KA), and N-methyl-Daspartate (NMDA). All three glutamate receptor subtypes are heteromultimeric complexes, and many of the subunits that comprise them have been identified and characterized. To date, four AMPA receptor subunits (GluRl-4), five KA receptor subunits (GluR5-7, KA1, and KA2), and six NMDA receptor subunits (NR1, NR2A-2D and NR3A) have been reported. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Freeze-dried preparation of n[o-(p-pivaloyloxybenzenesulfonylamino) benzoyl] glycine monosodium salt tetrahydrate and process for producing the same Inventor(s): Sudo, Masao; (Osaka, JP), Takada, Akira; (Osaka, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Suite 800; Washington; DC; 20037; US Patent Application Number: 20040092587 Date filed: May 22, 2003 Abstract: A method for the preparation of a freeze-dried product of N-[o-(ppivaloyloxybenzenesulfonylamino)benzoyl]glycine monosodium salt tetra-hydrate dissolved in a mixed solvent of water and ethanol, and the freeze-dried product obtained by the method.According to the present invention, N-[o-(ppivaloyloxybenzenesulfonylamin- o)benzoyl]glycine monosodium salt tetra-hydrate is dissolved in a small amount of a mixed solvent of water and ethanol, and therefore it is possible to manufacture high-dosage product by freeze-drying. Excerpt(s): The present invention relates to a freeze-dried product of N-[o-(ppivaloyloxybenzenesulfonylamino)benzoyl]glycine monosodium salt tetra-hydrate and a process for the manufacture thereof, characterized by using a mixed solvent of water and ethanol. (at times abbreviated as compound (I)) is described in example 3 of JP kokai hei 5-194366 (i.e. EP 539223) and in reference example 1 of JP kokai hei 9-40692 (no EP publication). Compound (I) has an inhibitory activity against elastase and is a very useful compound which is expected to be used for the treatment of acute pulmonary disorders. Since those patients suffering from acute pulmonary disorders are in a serious condition, it is necessary to administer a drug parenterally, preferably as an injection for a long time (from 24 hours to several days) continuously. Therefore compound (I) is appropriately formulated as an injection or a solid composition to be dissolved before administration, more preferably formulated as a freeze-dried product. And considering the convenience, a high-dosage product in a small vial compared with the amount of active ingredient is preferable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Genetic sequences encoding dominant-negative chalcone synthase and uses therefore Inventor(s): Choi, Giltsu; (Kwangju, KR), Choi, Goh; (Kwangju, KR), Hanummappa, Mamatha; (Kwangju, KR) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20040038407 Date filed: August 21, 2002 Abstract: The invention includes modified Mazus chalcone synthase (CHS) nucleic acids, which encode a modified chalcone synthase that has alanine instead of cysteine at the 165.sup.th amino acid of Mazus CHS and either glycine or lysine instead of methionine at the 138.sup.th amino acid of Mazus CHS. The property of the encoded modified Mazus CHS is characterized by its dominant-negative inhibition of CHS. The invention also includes plants having at least one cell expressing the modified Mazus CHS. Such plants are characterized by the decreased content of anthocyanins. The invention also includes vectors comprising at least a portion of the modified Mazus CHS
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nucleic acids. The invention also includes methods using such vectors for producing plants having the decreased content of anthocyanins. Excerpt(s): The invention relates to modified Mazus CHS nucleic acids that encode modified CHS enzymes that inhibit CHS dominant-negatively and their uses for genetically altering plants to decrease the content of anthocyanins in the plants. Flower color is an important horticultural trait and is mainly produced by the flavonoid pigments, anthocyanins. Primarily produced to attract pollinators, flavonoids also protect the plant and its reproductive organs from UV damage, pests and pathogen (Brouillard and Cheminat, 1988; Gronquist et al., 2001). Classical breeding methods have been extensively used to develop cultivars with flowers varying in both the color and its intensity. The recent advance of knowledge on flower coloration at the biochemical and molecular level has made it possible to achieve this by genetic engineering (Tanaka et al., 1998). Genetic engineering to alter flower color has been attempted using various genes. Some species lack a particular color due to the absence of a biosynthetic gene or the substrate specificity of an enzyme in the pathway. For example, carnation lacks blue/purple colored flowers due to the absence of F3'5'H, while petunia lacks orange and brick-red flowers due to the inability of its DFR to reduce DHK (Gerats et al., 1982; Forkmann and Ruhnau, 1987). Genetic engineering of blue/purple colored carnation was achieved by introducing petunia F3'5'H gene and orange-colored petunia was developed by introducing DFR from other species (Meyer et al., 1987; Brugliera et al., 2000; Johnson et al., 2001). The modulation of color intensity has been another target for genetic engineering. Expression of biosynthetic genes such as CHS, F3H, and DFR in sense or antisense directions has been the most exploited method (van der Krol et al., 1990; Courtney-Gutterson et al., 1994; Jorgensen et al., 1996; Tanaka et al., 1998). The resulting sense suppression or antisense inhibition is collectively called posttranscriptional gene silencing (PTGS). Though these approaches have been fairly successful in the down-regulation of pigment synthesis, the necessity of cloning the gene of interest from a specific species or closely related species is the major drawback. Further, it is difficult to limit the PTGS to specific tissues (Palauqui et al., 1997; Voinnet and Baulcombe, 1997; Voinnet et al., 1998; Fagard and Vaucheret, 2000; Crete et al., 2001; Vaucheret et al., 2001). Alternatively, transcription factors that can either activate or repress the transcription of anthocyanin biosynthetic genes have been shown to be useful in regulating color intensity in model plants such as Arabidopsis, tobacco, and Petunia (Lloyd et al., 1992; Mol et al., 1998; Borevitz et al., 2000; Aharoni et al., 2001). The overexpression of transcription factors, however, generally alters the expression of many genes, thus the commercial viability of such transgenic flowers has yet to be determined (Lloyd et al., 1994; Bruce et al., 2000). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Glycine betaine and its use Inventor(s): Messadek, Jallal; (Liege, BE) Correspondence: Hovey Williams Llp; Suite 400; 2405 Grand Boulevard; Kansas City; MO; 64108; US Patent Application Number: 20040033223 Date filed: August 4, 2003 Abstract: The present invention provides pharmaceutical uses of betaines, and especially glycine betaine, such as for the treatment of thromboses not induced by
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hyperhomocystenemia or homocystinuria, of blood disorders, such as blood coagulation and thrombi formation. Excerpt(s): This application is a continuation-in-part of co-pending U.S. application Ser. No. 09/945,391 filed Aug. 31, 2001 which is a continuation-in-part and claims priority from International Application No. PCT/BE00/00021 filed Mar. 1, 2000 claiming priority from Belgium Application Serial No. BE99/00144 Filed Mar. 2, 1999, and a continuation-in-part of International Application No. PCT/BE02/00013 filed Feb. 4, 2001 claiming priority from Belgium application Serial No. 2001/0085 filed Feb. 5, 2001, U.S. application Ser. No. 09/945,391 filed Aug. 31, 2001 and International Application No. PCT/BE01/00222 filed Dec. 21, 2001. The teachings and content of all of the foregoing are hereby incorporated by reference. This invention relates to the use of glycine betaine to eliminate physiopathological vascular attacks. The invention relates to the curative and preventive activity of glycine betaine in the pathogenesis of thrombo-embolic and haemostatic diseases of arterial or venous origin. Glycine betaine exhibits preventive activity while preventing the formation of thrombi and exhibits a curative activity that prevents the proliferation of thrombi while destroying them. The significance of the present invention is based on the fact that the use of glycine betaine does not result in any risk of haemorrhage or allergy in opposition to the molecules and treatments currently used. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Glycine N-methyltransferase monoclonal antibodies and methods of use therefor Inventor(s): Chen, Yi-Ming A.; (Taipei, TW) Correspondence: Rosenberg, Klein & Lee; 3458 Ellicott Center Drive-Suite 101; Ellicott City; MD; 21043; US Patent Application Number: 20040101913 Date filed: November 22, 2002 Abstract: The present invention provides two unique monoclonal antibodies directed against a portion of the human Glycine N-methyltransferase, and methods of use for the monoclonal antibodies in detecting, monitoring and diagnosing malignancies characterized by down-regulation of expression or inappropriate expression of the Glycine N-methyltransferase. Excerpt(s): This invention relates generally to the field of detecting, monitoring and diagnosing malignancies characterized by down-regulation of expression or inappropriate expression of the Glycine N-methyltransferase. Hepatocellular carcinoma (HCC) is one of the world's most common malignancies, causing almost one million deaths annually. HCC has a heterogeneous geographical distribution, which is probably related to differences in prevalence of risk factors among separate world areas. It is one of the most frequently occurring neoplasms in Asia, Africa and the Mediterranean basin. The incidence of hepatocellular carcinoma is higher in areas with high carrier rates of hepatitis B and C and in patients with haemochromatosis. More than 80% of hepatocellular carcinomas occur in patients with cirrhotic livers. Once viral infection is established, about 10 years are required for patients to develop chronic hepatitis, 20 years to develop cirrhosis, and 30 years to develop carcinoma. In African and Asian countries, aflatoxin produced as a result of contamination of imperfectly stored staple crops by Apergillus flavus seems to be an independent risk factor for the development of hepatocellular carcinoma, probably through mutation of the p53 suppressor gene.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Glycine-enriched vegetable compound feed for a broiler chicken Inventor(s): Iwasaki, Kazuya; (Kagoshima-ken, JP), Miura, Hiroshi; (Tochigi-ken, JP), Suzuki, Tamotsu; (Tochigi-ken, JP), Takahashi, Yoshinori; (Tochigi-ken, JP) Correspondence: Flynn Thiel Boutell & Tanis, P.C.; 2026 Rambling Road; Kalamazoo; MI; 49008-1699; US Patent Application Number: 20040028771 Date filed: August 9, 2002 Abstract: There is disclosed herein a glycine-enriched vegetable compound feed for a broiler chicken which causes an effect to suppress or prevent the occurrence of loose passage.According to the present invention, there is provided a glycine enriched vegetable compound feed for a broider chicken which comprises incorporated glycine into a vegetable compound feed in the range of 0.05-0.3% by weight based on the feed. Excerpt(s): The present invention relates to a feed for preventing the aggravation of chicken house environment and the lowering in the productivity caused by broiler chicken suffering from loose passage. In general, when a broiler chicken suffers from symptom of loose passage, it is susceptive to various bad influences. Under such circumstance, the floor surface material consisting of a rice hull becomes wet to cause the aggravation of the chicken house environment. In this connection, it becomes hard upon drying thereby causing the increase in the occurrence rate of chicken with weak legs and of disease inducing the formation of callosity in the breast of the chicken and so on. Also, since such fowl droppings are hard to treat because of their high water content and hence much labor is required for the treatment. When especially a vegetable compound feed is fed to a broiler chicken, there occurs a phenomenon that the chicken tends to suffer from loose passage. As an appropriate means to prevent the occurrence of loose passage, adjustment of mineral balance has been taken. In case of feed wherein the sodium content is excessive, the amount of drinking water is increased thereby causing the occurrence of loose passage. In case of complete vegetable protein raw material containing especially soybean meal, since it contains a large amount of potassium, the occurrence of loose passage has been considered to be due to the excess of monovalent cation and as the countermeasure are reported the reduction in the sodium content in the feed, the neutralization effect by conversion of sodium into sodium bicarbonate, etc. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Hydrophilic chemilumescent acridinium labeling reagents Inventor(s): Evangelista, Ramon; (Laguna Hills, CA), Garrity, Martha; (San Clemente, CA) Correspondence: Foley & Lardner; P.O. Box 80278; San Diego; CA; 92138-0278; US Patent Application Number: 20040038294 Date filed: August 20, 2002 Abstract: In accordance with the present invention, it has been discovered that introduction of hydrophilic sulfoalkyl substituents and/or hydrophilic linkers derived
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from homocysteic acid, cysteic acid, glycine peptides, tetraethylene oxide, and the like, offset the hydrophobicity of the acridinium ring system to produce a more soluble label which can be attached to an antibody at higher loading before precipitation and aggregation problems are encountered. Additional compounds described herein contain linkers derived from short peptides and tetraethylene oxide which increase aqueous solubility due to hydrogen bonding with water molecules. The present invention also embraces reagents for multiple acridinium labeling for signal amplification composed of a peptide bearing several acridinium esters with sulfonate groups at regularly spaced intervals for increased solubility. The invention also embraces assays employing the above-described compounds. Excerpt(s): The present invention relates to amine-reactive acridinium labeling reagents. In a particular aspect, the present invention relates to acridinium labeling reagents having one or more hydrophilic substituents thereon. In another aspect, the present invention relates to conjugates containing invention acridinium labeling reagents, kits containing same, and assays employing same. The following description of the background of the invention is provided simply as an aid in understanding the invention and is not admitted to describe or constitute prior art to the invention. Chemiluminescence immunoassays which employ acridinium labels have advantages of high throughput and high analytical sensitivity for low-level analytes of clinical significance. Usually it is desirable to use labeled antibodies with a large number of chemiluminescent tags, which produce high luminescence counts, which, in turn, allows one to achieve lower detection limits. This holds true provided that non-specific binding can be minimized. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Hydrophilic coating and a method for the preparation thereof Inventor(s): Madsen, Niels Joergen; (Alleroed, DK) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20040086722 Date filed: January 24, 2003 Abstract: A hydrophilic coating having a covalently cross-linked hydrophilic polymer suitable for coating medical devices or instruments for introduction into human cavities, the coating further having a water soluble compound, the water soluble compound being glucose, sorbitol a halide, nitrate, acetate, citrate or benzoate of an alkali metal or alkaline earth metal or silver; acetic acid, glycine or urea. A medical device or instrument for introduction into human cavities having a hydrophilic coating and a method of producing such a medical device or instrument. Excerpt(s): The present invention relates to a hydrophilic coating. Furthermore, the invention relates to a medical device provided with such a hydrophilic coating and a method for providing a medical device or other product with a hydrophilic coating as well as the use of a water soluble compound in the preparation of a medical device or instrument comprising a hydrophilic coating which is crosslinked. It is known to coat medical devices, e.g., catheters for introduction into human cavities such as blood vessels, digestive organs and the urinary system, with a hydrophilic coating, normally at a minimum applied on that part of the surface which is introduced or comes into contact with mucous membranes, etc., during introduction of the device. Although such coating
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is not particularly smooth when dry, so that the handling of the device is not inconvenient, it becomes extremely slippery when it is swelled with water, preferably immediately before introduction into the human body and thus ensures a substantially painless introduction with a minimum of damage on tissue. A large number of methods are known for the production of hydrophilic surface coatings. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for synthesizing peptides comprising at least one glycine molecule Inventor(s): Becu, Frank; (Zwevezele-Wingene, BE), Borremans, Frans; (Destelbergen, BE), Callens, Roland; (Grimbergen, BE) Correspondence: Connolly Bove Lodge & Hutz, Llp; P O Box 2207; Wilmington; DE; 19899; US Patent Application Number: 20040077830 Date filed: October 2, 2003 Abstract: Method for preparing a peptide or a peptide derivative comprising at least 2 enantiopure amino acids and at least one glycine molecule, comprising the reaction of a compound of general formula XCH.sub.2--C(.dbd.O)--HN--A- --COOY (II) with a compound of general formula HNR.sup.1R.sup.2 (III). Excerpt(s): The present invention relates to a method for synthesizing peptides or peptide derivatives comprising at least one glycine molecule, to some peptides or peptide derivatives and to some intermediates which can be used in the method of synthesis, and to their production. The peptides or peptide derivatives comprising at least one glycine molecule are of use, for example, as medicinal products, as intermediates for producing peptides and as a spacer arm in pharmaceutical compositions intended to take biologically active principles specifically to certain cells of the body. A specific example of such a peptide is Gly-Phe-Leu-Gly. In the state of the art (J. Chem. Educ, 1999, p. 1558-60) it is illustrated that the synthesis of this tetrapeptide starting from readily accessible products such as amino acids requires many protection, deprotection and coupling operations. The object of the invention is in particular to provide an efficient and economical method for synthesizing this peptide. Patent Application EP-A-0950664 describes the production of N-glycyl-L-tyrosine by reacting N-chloroacetyl-L-tyrosine in the presence of ammonium ions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Methods and kit for treating Parkinson's disease Inventor(s): Schneider, Jay S.; (Cherry Hill, NJ) Correspondence: Drinker Biddle & Reath; One Logan Square; 18th And Cherry Streets; Philadelphia; PA; 19103-6996; US Patent Application Number: 20040087596 Date filed: September 11, 2003 Abstract: The efficacy of levodopa therapy in patients being treated for Parkinson's disease is enhanced by administering high doses of a partial glycine agonist. The frequency and severity of levodopa-induced side effects in Parkinson's disease patients are also reduced by administration of a partial glycine agonist.
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Excerpt(s): This application claims the benefit of co-pending U.S. provisional application serial No. 60/410,512, filed on Sep. 13, 2002, the entire disclosure of which is herein incorporated by reference. The invention relates to therapies for Parkinson's Disease ("PD"), and in particular to methods and a kit for enhancing the efficacy of levodopa treatment and reducing levodopa-induced side effects with high doses of a partial glycine agonist. Parkinson's disease is a progressive disorder of the central nervous system affecting over 1.5 million people in the United States. Parkinson's disease is caused by the degeneration of the pigmented neurons in the substantia nigra of the brain, resulting in decreased dopamine availability to the striatum. Clinically, the disease is characterized by a decrease in spontaneous movements, gait difficulty, postural instability, rigidity and tremor. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for treatment of erectile dysfunction Inventor(s): Podolski, Joseph S.; (The Woodlands, TX) Correspondence: IP Prosecution; Howrey Simon Arnold & White, Llp; Box NO. 34; 1299 Pennsylvania Avenue, N.W.; Washington; DC; 20004-2402; US Patent Application Number: 20040102475 Date filed: November 3, 2003 Abstract: Improved drug compositions and methods useful in the treatment of male erectile dysfunction. An optimized mixture of the drugs phentolamine mesylate, papaverine hydrochloride, and alprostadil in a buffer containing L-arginine and glycine is to be injected into the penile tissue to produce an erection in otherwise impotent men. Excerpt(s): This invention relates to improved drug compositions useful in the treatment of male erectile dysfunction and also to methods of treatment. More particularly, this invention discloses specific formulations containing the pharmacological agents phentolamine mesylate, papaverine hydrochloride, and alprostadil (prostaglandin E1) in a novel buffer and the administration of such formulations to mammals (including humans) to treat male impotence. Impotence is a common medical disorder affecting about 20 million men in the U.S. alone. Male erectile dysfunction has been defined as the inability to achieve or maintain an erection sufficient for intercourse (Impotence, National Institutes of Health Consensus Development Panel on Impotence Conference, JAMA 1993, 270, 83-90). The dominant etiology for this condition is arterial insufficiency associated with cardiovascular disease. Male erectile dysfunction adversely impacts the quality of life, being frequently associated with depression, anxiety, and low self-esteem. Although male erectile dysfunction represents a major clinical problem, treatment for this condition remains problematic and unsatisfactory. One of the least invasive therapies available entails the use of a vacuum constriction-device on the penis to produce an erection. The physiology of the penis is such that blood flows in through arteries deep within the tissue while blood flows out through veins near the skin surface. By placing a plastic cylinder over the shaft of the penis and employing a vacuum pump to restrict venous blood flow from the penis, the corpus cavernosum penile tissue becomes engorged with trapped blood and an erection is produced. Common patient complaints are that this device is interruptive to the sex act, has a short duration of effectiveness, and can cause tissue damage to the penis, such as necrosis, with extended use. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Molecules that block viral infectivity and methods of use thereof Inventor(s): GOOBAR-LARSSON, LAURA; (STOCKHOLM, SE), VAHLNE, ANDERS; (STOCKHOLM, SE) Correspondence: Knobbe Martens Olson & Bear Llp; 2040 Main Street; Fourteenth Floor; Irvine; CA; 92614; US Patent Application Number: 20040038908 Date filed: April 1, 2003 Abstract: Embodiments relate to the discovery that certain tripeptide amides and glycine amide can be used to inhibit viral infection, including human immunodeficiency virus (HIV) infection. More specifically, medicaments comprising said tripeptide amides and/or glycine amide and methods of using said compounds for the prevention and treatment of viral infection, such as HIV infection, are provided. Excerpt(s): This application is a continuation of U.S. application Ser. No. 10/235,158, filed Sep. 03, 2002, which claims priority to U.S. Provisional Application No. 60/323,650, filed Sep. 19, 2001. This application claims priority to U.S. application Ser. No. 10/235,158 and U.S. Provisional Application No. 60/323,650, both of which are hereby expressly incorporated by reference in their entireties. The present invention relates to the discovery that certain tripeptide amides and glycine amide can be used to inhibit viral infection, including human immunodeficiency virus (HIV) infection. More specifically, medicaments comprising these tripeptide amides and glycine amide and methods of using said compounds for the prevention and treatment of viral infection, such as HIV infection, are provided. All viruses are composed of a protein shell surrounding a nucleic acid containing core. The protein shell directly surrounding the viral nucleic acid is called a capsid, whereas, the complete protein-nucleic acid complex having both the capsid and the nucleic acid is called a nucleocapsid. Arenaviruses, rotaviruses, orbiviruses, retroviruses (including lentiviruses), papillomaviruses, adenoviruses, herpesviruses, paramyxovirus, myxovirus, and hepadnaviruses all exhibit these general structural features. (Virology, Fields ed., third edition, Lippencott-Raven publishers, pp 1513, 1645, 1778, 2047, 2113, 2221, and 2717 (1996)). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Mutations of the mdr1 p-glycoprotein that improves its ability to confer resistance to chemotherapeutic drugs Inventor(s): Roninson, Igor; (Cohoes, NY), Ruth, Adam; (Chicago, IL) Correspondence: Mcdonnell Boehnen Hulbert & Berghoff; 300 South Wacker Drive; Suite 3200; Chicago; IL; 60606; US Patent Application Number: 20040086882 Date filed: October 17, 2003 Abstract: The present invention provides mutant P-glycoprotein polypeptides that confer increased resistance to certain chemotherapeutic drugs relative to wild-type Pglycoprotein or P-glycoprotein having a glycine to valine substitution at position 185, and nucleic acid molecules encoding the same. The invention also provides antibodies that specifically bind mutant P-glycoproteins. The invention further provides methods
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for the diagnosis and treatment of conditions associated with P-glycoprotein-mediated multidrug resistance. Excerpt(s): This application claims the benefit of priority from U.S. Provisional Patent Application No. 60/222,313, filed on Aug. 1, 2000, the disclosure of which is explicitly incorporated by reference herein. The invention relates to mutant human P-glycoprotein polypeptides that confer increased resistance to certain chemotherapeutic drugs compared to wild-type P-glycoprotein or P-glycoprotein having a glycine to valine substitution at position 185, and nucleic acid molecules encoding the same. The invention also relates to antibodies that specifically bind mutant human P-glycoproteins. The invention further relates to methods for diagnosis and treatment of conditions associated with P-glycoprotein-mediated multidrug resistance. Multidrug resistance (MDR) is a phenomenon in which a cell becomes resistant to a large group of structurally diverse chemotherapeutic drugs that act at different intracellular targets. One mechanism of MDR1 in clinical cancer is active drug efflux mediated by a cellular protein termed P-glycoprotein. P-glycoprotein is an integral membrane protein having six transmembrane domains and consisting of 1280 amino acids (SEQ ID NO: 2), which functions as a broad specificity efflux pump. The protein is composed of two structurally similar portions, of approximately 600 amino acids each, which are separated by a linker region. Human P-glycoprotein is encoded by the MDR1 gene (Chen et al., 1986, Cell 47:381-89), the wild-type cDNA sequence of which is identified herein as SEQ ID NO: 1. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Nitrogen-containing compounds and their use as glycine transport inhibitors Inventor(s): Ali, Syed M.; (Solon, OH), Brunden, Kurt R.; (Aurora, OH), Jiang, Jack B.; (Village, OH) Correspondence: Wood, Phillips, Katz, Clark & Mortimer; 500 W. Madison Street; Suite 3800; Chicago; IL; 60661; US Patent Application Number: 20040034069 Date filed: August 8, 2003 Abstract: A method for the inhibition of high affinity glycine transporters, compounds that inhibit these transporters; pharmaceutically active compositions comprising such compounds; and the use of such compounds either as above, or in formulations for the control or prevention of disease states in which glycine is involved are disclosed. Excerpt(s): This invention is directed generally to nitrogen-containing compounds and pharmaceutically acceptable salts thereof. The compounds are inhibitors of high affinity glycine transporters and are thus useful in treating neurological disorders including schizophrenia, dementia, epilepsy, muscle spasticity, mood disorders, learning disorders, neurodegenerative diseases and pain. Glycine acts as a neurotransmitter at two distinct receptor systems. In the spinal cord and certain non-cerebral brain regions, glycine acts much like GABA (.gamma.-amino-n-butyric acid) in causing the opening of an inhibitory Cl.sup.- channel. This activity is mediated by the "strychnine-sensitive" glycine receptor. Glycine also acts as a co-agonist at the NMDA (N-methyl-D-aspartate) glutamate receptor that is localized in the cognitive centers of the brain, including the cortex, hippocampus, and basal ganglia. This receptor has received considerable attention from the pharmaceutical industry since there is compelling evidence that it plays a critical role in learning and cognition. Furthermore, excessive stimulation of the
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NMDA receptor appears to be responsible for much of the neuronal damage that occurs after stroke-injury and brain trauma. Hence, there are ongoing research efforts to develop both agonists (for increased cognition) and antagonists (for treatment of stroke) to the NMDA receptor. Recent data suggest that agonists and antagonists to the glutamate site of the NMDA receptor can cause relatively severe side-effects. For example, NMDA antagonists have been shown to cause agitation, hallucinations, and paranoia in stroke patients. Agonists to the glutamate binding site on NMDA receptors have the potential of causing excessive calcium influx and excitotoxic cell damage. In contrast, the glycine site on the NMDA receptor appears to play a modulatory role, and therefore compounds interacting with this site do not appear to evoke such severe sideeffects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel albumin-free factor VIII formulations Inventor(s): Besman, Marc; (Studio City, CA), Bjornson, Erik; (Studio City, CA), Carpenter, John; (Littleton, CO), Jameel, Feroz; (Covina, CA), Kashi, Ramesh; (Walnut, CA), Pikal, Michael; (Mansfield Center, CT), Tchessalov, Serguei; (Ashford, CT) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20040116345 Date filed: July 1, 2003 Abstract: A Factor VIII composition formulated without albumin, comprising the following formulation excipients in addition to Factor VIII: 4% to 10% of a bulking agent selected from the group consisting of mannitol, glycine and alanine; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. Alternatively, the formulation can comprise 2% to 6% hydroxyethyl starch; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; 100 mM to 300 mM NaCl; and a buffering agent for maintaining a pH of approximately between 6 and 8. In a further embodiment, the formulation can comprise: 300 mM to 500 mM NaCl; 1% to 4% of a stabilizing agent selected from the group consisting of sucrose, trehalose, raffinose, and arginine; 1 mM to 5 mM calcium salt; and a buffering agent. Excerpt(s): This application is a continuation-in-part of copending U.S. patent application Ser. No. 09/255,279, filed Feb. 22, 1999, which is a continuation-in-part of copending U.S. patent application Ser. No. 09/452,752, filed Dec. 1, 1999. The entire contents of both of these applications are hereby incorporated by reference. Factor VIII is a protein found in blood plasma which acts as a cofactor in the cascade of reactions leading to blood coagulation. A deficiency in the amount of Factor VIII activity in the blood results in the clotting disorder known as hemophilia A, an inherited condition primarily affecting males. Hemophilia A is currently treated with therapeutic preparations of Factor VIII derived from human plasma or manufactured using recombinant DNA technology. Such preparations are administered either in response to a bleeding episode (on-demand therapy) or at frequent, regular intervals to prevent uncontrolled bleeding (prophylaxis). Factor VIII is known to be relatively unstable in therapeutic preparations. In blood plasma, Factor VIII is usually complexed with another plasma protein, von Willebrand factor (vWF), which is present in plasma in a
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large molar excess to Factor VIII and is believed to protect Factor VIII from premature degradation. Another circulating plasma protein, albumin, may also play a role in stabilizing Factor VIII in vivo. Currently marketed Factor VIII preparations therefore primarily rely on the use of albumin and/or vWF to stabilize Factor VIII during the manufacturing process and during storage. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel n(phenylsulphonyl)glycine derivatives and their therapeutic use Inventor(s): Barth, Martine; (Asnieres Les Dijon, FR), Bondoux, Michel; (Fontaine Les Dijon, FR), Dodey, Pierre; (Fontaine Les Dijon, FR), Luccarini, Jean-Michel; (Dijon, FR), Matt, Christophe; (Neuville Sur Saone, FR), Paquet, Jean-Luc; (Brognon, FR), Pruneau, Didier; (Pasques, FR) Correspondence: Merchant & Gould PC; P.O. Box 2903; Minneapolis; MN; 55402-0903; US Patent Application Number: 20040063725 Date filed: June 20, 2003 Abstract: The present invention relates to novel N-(phenylsulphonyl)glycyl-glycine compounds, which are defined by formula I and the description, as well as their method of preparation and their use in therapeutics 1 Excerpt(s): The present invention relates to novel N-(phenylsulphonyl)glycine compounds, their method of preparation and their use for obtaining pharmaceutical compositions. These novel compounds are useful in therapeutics, particularly for treating pain. Compounds having an arylsulphonamide-type group and glycine in their structure are already known. N-.alpha.-arylsulphonylaminoacyl-p-ami- dinophenylalaninamides, which are selective inhibitors of thrombin and which are useful as antithrombotics, can be cited for example, from EP 236 163 and EP 236 164. Compounds of structure quite close to the preceding ones, simultaneously comprising an arylsulphamoyl group and a substituted phenylamidine group, which have the property of binding to neuropeptide Y receptors and which can be useful for treating hypertension, angina, atherosclerosis, depression, anxiety, inflammation, allergy or fatty excess weight, are also known, from EP 614 911. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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N-substituted glycine derivatives Inventor(s): Lauffer, David; (Stow, MA), Ledford, Brian; (Hopkinton, MA), Mullican, Michael; (Needham, MA) Correspondence: Vertex Pharmaceuticals INC.; 130 Waverly Street; Cambridge; MA; 02139-4242; US Patent Application Number: 20040072821 Date filed: October 2, 2003 Abstract: The present invention relates N-substituted glycine derivatives for treating or preventing neuronal damage associated with neurological diseases. The invention also provides compositions comprising the compounds of the present invention and methods of utilizing those compositions for treating or preventing neuronal damage.
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Excerpt(s): Neurological diseases are associated with the death of or injury to neuronal cells. Typical treatment of neurological diseases involves drugs capable of inhibiting neuronal cell death. A more recent approach involves the promotion of nerve regeneration by promoting neuronal growth. Neuronal growth, which is critical for the survival of neurons, is stimulated in vitro by nerve growth factors (NGF). For example, Glial Cell Line-Derived Neurotrophic Factor (GDNF) demonstrates neurotrophic activity both, in vivo and in vitro, and is currently being investigated for the treatment of Parkinson's disease. Insulin and insulin-like growth factors have been shown to stimulate growth of neurites in rat pheochromocytoma PC12 cells and in cultured sympathetic and sensory neurons [Recio-Pinto et al., J. Neurosci., 6, pp. 1211-1219 (1986)]. Insulin and insulin-like growth factors also stimulate the regeneration of injured motor nerves in vivo and in vitro [Near et al., Proc. Natl. Acad. Sci., pp. 89, 11716-11720 (1992); and Edbladh et al., Brain Res., 641, pp. 76-82 (1994)]. Similarly, fibroblast growth factor (FGF) stimulates neural proliferation [D. Gospodarowicz et al., Cell Differ., 19, p. 1 (1986)] and growth [M. A. Walter et al., Lymphokine Cytokine Res., 12, p. 135 (1993)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Peptides from the E2, E6, and E7 proteins of human papilloma viruses 16 and 18 for detecting and/or diagnosing cervical and other human papillomavirus associated cancers Inventor(s): Hu, Yao Xiong; (Mountain View, CA), Rosenfeld, Mark Jay; (Draper, UT) Correspondence: Pate Pierce & Baird; 215 South State Street, Suite 550; Parkside Tower; Salt Lake City; UT; 84111; US Patent Application Number: 20040110925 Date filed: July 1, 2003 Abstract: An isolated protein sequence or peptide from the E2, E6 or E7 early coding region of human papillomavirus (HPV) that is soluble in an aqueous medium, and characterized by a relative paucity of tryptophan, methionine and cysteine residues, and a relative abundance of glycine and asparagine residues. Also disclosed are isolated protein sequences or peptides from the E2, E6 or E7 early coding regions of HPV 16 and 18 and methodologies for detecting or diagnosing cancer or cellular abnormalities. Detection or diagnosis of Cancer or cellular abnormalities may include detecting or diagnosing pre-cancerous or pre-malignant conditions, cervical dysplasia, cervical carcinoma, koilocytosis, hyperkeratosis, intraepithelial lesions, and other cancers. A methodology for detecting or diagnosing cancer or cellular abnormalities comprises the steps of (1) reacting a sample of body fluid or tissue with isolated protein sequences or peptides; (2) forming an antibody-peptide complex; and (3) detecting the antibodypeptide complex. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/394,172, filed Jul. 2, 2002, and entitled "NOVEL PEPTIDES FROM THE E2, E6 AND E7 PROTEINS OF HUMAN PAPILLOMAVIRUSES 16 AND 18 FOR DIAGNOSING OR DETECTING CERVICAL AND OTHER HUMAN PAPILLOMAVIRUS ASSOCIATED CANCERS" and co-pending U.S. patent application Ser. No. 09/828,645, filed Apr. 5, 2001, and entitled "IMMUNOLOGICAL METHODOLOGY FOR DISCERNING HUMAN PAPILLOMAVIRUS," which are incorporated herein by reference. The present invention relates generally to the field of peptides reactive with antibodies formed against human papillomavirus (HPV). Some have termed this type of peptide as antigenic or immunoreactive. More particularly, the invention relates to peptides
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isolated, purified or derived from the early coding region of the E2, E6, and E7 oncoproteins of HPV and method for use for the detection and/or diagnosis of HPV associated epithelial cell abnormalities, precancerous conditions and cancers via an immunoassay. The human papillomaviruses (HPV), named because certain types induce warts or papillomas, cause virtually all cervical cancers (Nobbenhuis et al., "Relation of human papillomavirus status to cervical lesions and consequences for cervical-cancer screening: a prospective study," The Lancet, 354:20-25, 1999; Cuzick et al., "A systematic review of the role of human papilloma virus (HPV) testing within a cervical screening programme: summary and conclusions," British Journal of Cancer, 83:561-565,2000). These encompass not only squamous cell carcinomas (Nobbenhuis et al., 1999) but also adenocarcinomas (Pirog et al., "Prevalence of human papillomavirus DNA in different histological subtypes of cervical adenocarcinoma," American Journal of Pathology, 157:1055-1062,2000). These viruses are also strongly associated with vulvar and vaginal carcinomas (Frisch et al., "Human papillomavirus-associated carcinomas in Hawaii and the mainland US," Cancer 88:1464-1469, 2000; Sugase et al., "Distinct manifestations of human papillomaviruses in the vagina," International Journal of Cancer, 72:412-415, 1997), as well as cancers of the anus (Frisch et al., 2000) and penis (Gregoire et al., "Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma," Journal of the National Cancer Institute, 87:1705-1709, 1995). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Pharmaceutical compositions containing an effervescent acid-base couple Inventor(s): Acerbi, Daniela; (Parma, IT), Brambilla, Gaetano; (Parma, IT), Chiesi, Paolo; (Parma, IT), Mezzadri, Rosa; (Parma, IT), Ventura, Paolo; (Parma, IT) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20040151768 Date filed: December 4, 2003 Abstract: A pharmaceutical composition in the form of effervescent tablets comprising an active ingredient and an effervescent blend, comprising an acidic component and sodium glycine carbonate as alkaline components. Preferred acid components are fumaric acid, maleic acid, and their salts. Tablets are prepared in normal thermohygrometric conditions and with standard tabletting equipment. A pregranulation process is also disclosed. Excerpt(s): This application is a Continuation-in-Part of U.S. application Ser. No. 09/932,097 filed Aug. 20, 2001 which is a Continuation-in-Part of U.S. application Ser. No. 09/463,224, filed Mar. 21, 2000, now U.S. Pat. No. 6,284,272, dated Sep. 4, 2001. The full text of those applications is incorporated herein by reference. This invention relates to orally administered, solid, fast-soluble pharmaceutical compositions containing an effervescent acid-base couple, suitable for dissolving in water or an aqueous solution and for sucking. The effervescent tablets occupy an important position among dosage forms, being the form of choice not only for adults but also for children. Many drugs, and in particular analgesics, vitamins and antibiotics were designed in this kind of formulations. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Pharmaceutical formulation consisting of a plant dry extract with a calcium coating Inventor(s): Popp, Michael A; (Neumarkt, DE) Correspondence: Stephan A Pendorf; Pendorf & Cutliff; 5111 Memorial Highway; Tampa; FL; 33634-7356; US Patent Application Number: 20040151781 Date filed: December 8, 2003 Abstract: Pharmaceutical formulation, its use, and method for its manufacture The present invention relates to a pharmaceutical formulation of a calcium salt and a dry plant extract in the form of a coated tablet, wherein it has a core of at least one dry plant extract, enveloped by at least one coating of at least one calcium salt. The plant extracts for the core may be selected from: Vitex agnus castus (chaste tree); Belamcanda chinensis (leopard lily); Cimicifuga racemosa (black cohosh); Trifolium pratense L. (purple trefoil); Oenothera biennis hom. (primrose); Glycine soja (soy bean); Serenoa repens (saw-palmetto); Urtica dioica (stinging nettle), in particular its root; Cucurbita pepo (pumpkin), in particular its seed; Pygeum africanum; as well as suitable mixtures of these. Excerpt(s): The present invention relates to a pharmaceutical formulation in accordance with the preamble of claim 1, a use thereof in accordance with claim 11, and a method for its manufacture in accordance with claim 13. 17.beta.-estradiol, which is naturally formed in the ovaries [also referred to as E.sub.2], has a general proliferation-enhancing action in humans and animals. In addition to controlling the female cycle, it has, i.a., a homeostatic effect on the metabolism of the bone, while also preventing the formation of atherotic plaques on vessel endothelia. During menopause, estradiol levels decrease due to cessation of ovarial function. In the absence of sufficiently high estradiol levels in the blood, the activity of the osteoclasts, and thus breakdown of the bone mass--so-called "osteoporosis"--predominates in the bone tissue, which is accompanied by an increased risk of skeletal breakage. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Poly(dipeptide) as a drug carrier Inventor(s): Xu, Wuhan Jingya; (Missouri, TX) Correspondence: Gilbreth & Associates, P.C.; PO Box 2428; Bellaire; TX; 77402-2428; US Patent Application Number: 20040121954 Date filed: September 9, 2003 Abstract: A novel polypeptide drug carrier is provided wherein polypeptides containing glutamic acid and aspartic acid, or glutamic acid/alanine, or glutamic acid/asparagine, or glutamic acid/glutamine, or glutamic acid/glycine, are conjugated to drugs in order to improve the solubility of the drugs and/or their therapeutic efficacy in vivo. An illustrative example involves the conjugation of paclitaxel to a poly(glutamic acid/aspartic acid) polypeptide and its efficacy in the treatment of prostate cancer in vivo. Excerpt(s): This patent application is a Continuation-in-part of copending U.S. patent application Ser. No. 10/104,480, filed Mar. 20, 2002, which is a Continuation of U.S. patent application Ser. No. 09/291,234, filed Apr. 13, 1999, both of which are incorporated herein by reference. The present invention relates to novel drug carriers and their use. More particularly, the present invention relates to the novel use of a
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poly(di-peptide) peptide covalently bound to a drug to act as a drug carrier, particularly for poorly water soluble drugs. The poly(dipeptide) may be composed of a combination of glutamic acid and aspartic acid. The poly(dipeptide) may be composed of combinations of glutamic acid with alanine, asparagine, glycine or glutamine. It is undisputed that advances in pharmaceuticals have revolutionized health care for humans and other animals as well. However, 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 paclitaxel in the treatment of tumors, especially for example, in the case of prostate cancer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Precursors of silk-like materials, silk-like materials and processes for producing both Inventor(s): Asakura, Tetsuo; (Tokyo, JP) Correspondence: Millen, White, Zelano & Branigan, P.C.; 2200 Clarendon BLVD.; Suite 1400; Arlington; VA; 22201; US Patent Application Number: 20040132957 Date filed: September 22, 2002 Abstract: A silk-like material precursor, a method of producing such a precursor and a silk-like material produced from such a precursor are provided.The silk-like material precursor is a copolymer represented by the general formula -[(GA.sup.1).sub.j((GA.sup.2).sub.k-G-Y-(GA.sup.3).sub.l).sub.m]-.sub.n-. In the module (GA.sup.1).sub.j, the precursor is organized in a repeated.beta.-turn type II structure having intramolecular hydrogen bonds formed successively along its molecular axis. In this formula, G represents glycine and A.sup.1 represents alanine, but it is also possible to replace every third A.sup.1 with serine. A.sup.2 and A.sup.3 both represent alanine, but these residues may be partly replaced with valine. Y represents an amino acid containing an asymmetric carbon atom giving water solubility to the precursor. Finally, j is an integer of at least 6, k and l are both integers of 0 to 5, m is an integer of 1 to 7 and n is an integer of at least 10. Excerpt(s): The present invention relates to precursors of silk-like material, a silk-like material produced therefrom, and methods of producing the same. Domestic silkworms (Bombyx mori silkworms) extrude liquid silk in a pre-fibrillation state and produce silk fibers with high strength and high elasticity within a very short time of spinning at room temperature. It is well known that fabric woven from such silk fibers has widely been praised for luxury clothing production. In addition, this kind of textile fabric is ecologically friendly since silk fibers are biodegradable. Therefore, in the past decades, natural silk has become the subject of extensive studies as model systems. Although the primary structure of Bombyx mori silk and the secondary structure of silk fibers (Silk II) have already been determined, the structure of silk before spinning (Silk I) and the conformational transition involved have not been clarified yet. Moreover, many attempts to produce such silk-like fibers with high strength and elasticity have been performed but none of them really succeeded. The primary structure of the silk fibroin produced by domestic silkworms has been reported by Zhou et al. (Zhou et al., Nucleic Acids Research, 28, 2413-2419 (2000)). According to this report, the crystalline repeated
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motifs (Gly-Ala-Gly-Ala-Gly-Ser)n and the semicrystalline motifs containing Tyr and/or Val are partly included in a chain of Gly-Ala linkage. Furthermore, both the ordered and the disordered domains are repeated in cycles. Besides, the structure of silk films (liquid silk extracted from the posterior silk glands and gently dried) has been studied on the atomic level by X-ray diffraction. In this case, the structure reported is namely Silk I. Synthesis and structural analysis of several model compounds of silk have also been performed. However, the Silk I structure still remain poorly characterized. Therefore, the precise mechanism of formation of silkworm silk fibers cannot be determined. Without this fundamental knowledge, it is undoubtedly difficult to produce silk-like fibers artificially. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Racemization of optically active 2-substituted phenyl glycine esters Inventor(s): Barde, Anup Ramkrishna; (Mumbai, IN), Joshi, Shreerang Vidyadhar; (Mumbai, IN), Maheshwari, Krishna K.; (Mumbai, IN), Ranade, Prasad Vasudeo; (Maharashtra, IN), Sarma, Rayaprolu Kodandarama; (Mumbai, IN), Sutar, Rajiv Pandurang; (Maharashtra, IN) Correspondence: Gibbons, Del Deo, Dolan, Griffinger & Vecchione; 1 Riverfront Plaza; Newark; NJ; 07102-5497; US Patent Application Number: 20040073057 Date filed: October 15, 2002 Abstract: A process for preparing racemic mixtures containing nearly equal amounts of stereo isomers of compounds of formula (I), or their salts, by heating an enantiomerically enriched material with thionyl chloride. 1A required useful enantiomer may thereby be recovered from unwanted mother liquors that would otherwise be otherwise be discarded. Excerpt(s): The present invention is also directed to a process for preparing racemic mixtures containing nearly equal amounts of enantiomers of 2-chlorophenyl glycine methyl ester from mother liquors enriched with unwanted isomers, as its hydrochloride salt, by heating the mother liquors with thionyl chloride. Racemization is generally carried out by heating an acid with or without the presence of an alkali or a solvent. Free amino acids are difficult to racemize. The temperature required for racemization is often in the range of 140.degree.-180.degree. C. and some decomposition occurs at temperatures within this high range. Decomposition is extensive with 2-(2chlorophenyl) glycine, not only because it is difficult to racemize, but also because it easily degrades. 2-(2-chlorophenyl) glycine is an intermediate required in its enantiomerically pure (S) enantiomer for the production of methyl alpha-5 (4,5,6,7tetrahydro (3,2,-c) thienopyridyl) (2chlorophenyl)-acetate) to produce an important active pharmaceutical ingredient known as clopidogrel. The enantiomerically pure form of 2(2-chlorophenyl) glycine is derived from its racemic mixture by optical resolution separation techniques. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Solid compositions suitable for oral administration containing non-hygroscopic salts of l-carnitine and the alkanoyl l-carnitines with taurine chloride and glycine chloride Inventor(s): Tinti, Maria Ornella; (Pomezia, IT) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20040024061 Date filed: April 30, 2003 Abstract: Described herein are both non-hygroscopic salts of L-carnitine and alkanoyl Lcarnitine with taurine chloride (2-aminoethane-sulphonic chloride) and non-hygroscopic salts of L-carnitine and alkanoyl L-carnitine with glycine chloride which lend themselves favourably to the preparation of solid compositions suitable for oral administration. Also described are solid compositions containing said salts. Excerpt(s): The invention described herein relates to physiologically acceptable salts of L-carnitine and alkanoyl L-carnitine, characterised in that they are non-hygroscopic and stable. Said salts lend themselves favourably to the preparation of solid compositions suitable for oral administration. The invention also relates to pharmaceutical and alimentary or nutritional compositions containing them. It is well known that carnitine and its alkanoyl derivatives lend themselves to various therapeutic uses. For example, L-carnitine is used in the cardiovascular field for the treatment of acute and chronic myocardial ischaemia, angina pectoris, heart failure and cardiac arrhythmias. In the nephrological field, L-carnitine is administered to uraemic patients on regular haemodialysis treatment to combat muscular asthenia and the onset of muscle cramps. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Spiro(2H-1benzopyran-2,4'-piperidine) derivates as glycine transport inhibitors Inventor(s): Gibson, Samuel George; (Lanarkshire, GB), Miller, David John; (Airdrie, GB) Correspondence: Intervet Inc; 405 State Street; PO Box 318; Millsboro; DE; 19966; US Patent Application Number: 20040029904 Date filed: August 8, 2003 Abstract: 1The present invention relates to spiro[2H-1-benzopyran-2,4'-piperidine] derivatives having general formula (I), or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, as well as to the use of these spiro[2H-1-benzopyran-2,4'-piperidine] derivatives in therapy, more specifically for the treatment of CNS disorders. Excerpt(s): The invention relates to spiro[2H-1-benzopyran-2,4'-piperidine] derivatives, to pharmaceutical compositions containing the same, as well as to the use of these spiro[2H-1-benzopyran-2,4'-piperidine] derivatives in therapy. The simplest x-amino acid glycine has a number of important roles in the mammalian central nervous system (CNS). Along with.gamma.-aminobutyric acid (GABA), it is a major post-synaptic inhibitory transmitter in the spinal cord and brainstem, acting through ligand gated ion channels. Interaction of glycine with these receptors can be antagonized by the alkaloid strychnine. These receptors are therefore referred to as `strychnine sensitive` glycine receptors. Glycinergic neurotransmission is important in the processing and control of visual, auditory and motor signalling. Glycine is also an obligatory co-agonist along with glutamate at the N-methyl-D-aspartate (NMDA) receptor. Glycine therefore
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functions in excitatory transmission by modulating the actions of glutamate, the major excitatory neurotransmifter in the CNS. In addition the amino acid plays a role in the metabolism of peptides and proteins, including the exchange of one-carbon units. Control of the availability of glycine for any of the above processes will potentially influence their function and provide means of treating a number of diseases and conditions. Apart from metabolism, one of the major processes controlling the concentrations of free glycine in the proximity of strychnine-sensitive and strychnineinsensitive glycine receptors is the functioning of selective high affinity glycine transporters. These proteins can actively limit the spread of glycine beyond the immediate environs of receptors, thus maintaining both spatial and temporal fidelity of receptor activation. Rapid sequestering of transmitter into neuronal or glial cells via the transporter will also conserve glycine for future release. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Substituted glycine derivatives for use as medicaments Inventor(s): Blakemore, David; (Sandwich, GB), Bryans, Justin S.; (Sandwich, GB), Chu, Wai-Lam Alex; (San Diego, CA), Maw, Graham N.; (Sandwich, GB), Rawson, David J.; (Sandwich, GB), Thompson, Lisa R.; (Sandwich, GB) Correspondence: David R. Kurlandsky; Warner-Lambert Company Llc; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20040092498 Date filed: August 13, 2003 Abstract: The compounds of formula (I) are substituted glycine derivatives useful in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, arthritis, neuropathological disorders, sleep disorders, visceral pain disorders and gastrointestinal disorders. Processes for the preparation of the final products and intermediates useful in the process are included. Pharmaceutical compositions containing one or more of the compounds are also included. 1wherein R.sup.1 is hydroxycarbonyl, a carboxylic acid biostere or prodrug thereof;R.sup.3, R.sup.3a, R.sup.2 and R.sup.2a are independently selected from H, C.sub.1-C.sub.6 alkyl, and C.sub.1-C.sub.6 alkoxy C.sub.1-C.sub.6 alkyl;Z is;(i) a C-linked, 5 membered heterocycloalky or heteroaryl substituted with C.sub.1-C.sub.6 alkyl or fused with C.sub.3-C.sub.8 cycloalkyl, 4-8 membered heterocycloalkyl, phenyl, or monocyclic heteroaryl, wherein the fused ring is optionally substituted with one or two substituents selected from the group consisting of halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, perfluoro C.sub.1-C.sub.6 alkyl, perfluoro C.sub.1-C.sub.6 alkoxy, cyano, C.sub.1-C.sub.6 alkyl amino, C.sub.1-C.sub.6 alkyl thio, C.sub.3-C.sub.8 cycloalkyl, 4-8 membered heterocycloalkyl, phenyl, and monocyclic heteroaryl; or(ii) the group; 2wherein R.sup.4 and R.sup.4a are independently H, C.sub.1-C.sub.6 alkyl, C.sub.1C.sub.6 alkoxy or C.sub.1-C.sub.6 alkoxy C.sub.1-C.sub.6 alkyl;R.sup.5 is C.sub.1C.sub.6 alkyl, C.sub.3-C.sub.12 cycloalkyl, 4-12 membered heterocycloalkyl, aryl or heteroaryl and R.sup.5 is optionally substituted with one or two substituents selected from the group consisting of halogen, C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkoxy, perfluoro C.sub.1-C.sub.6 alkyl, perfluoro C.sub.1-C.sub.6 alkoxy, cyano, C.sub.1C.sub.6 alkyl amino, di-C.sub.1-C.sub.6 alkyl amino, amino C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkyl amino C.sub.1-C.sub.6 alkyl, di-C.sub.1-C.sub.6 alkyl amino C.sub.1-C.sub.6 alkyl, C.sub.1-C.sub.6 alkyl thio, C.sub.3-C.sub.8 cycloalkyl, 4-8
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membered heterocycloalkyl, phenyl and monocyclic heteroaryl; and either;(i) Y is S, O, NH or CH.sub.2 and X is a direct link or C.sub.1-C.sub.2 alkyl optionally substituted with C.sub.1-C.sub.6 alkyl or di-C.sub.1-C.sub.6 alkyl or 1-4 fluorine atoms; or(ii) X is S, O, CH.sub.2 or NH and Y is C.sub.1-C.sub.2 alkyl optionally substituted with C.sub.1C.sub.6 alkyl or di-C.sub.1-C.sub.6 alkyl or 1-4 fluorine atoms. Excerpt(s): This United States Utility Application claims the benefit of United Kingdom Application Number 0219153.4 filed on Aug. 16, 2002 and U.S. Provisional Application No. 60/413,856 filed on Sep. 25, 2002. The invention relates to substituted glycine derivatives useful as pharmaceutical agents, to processes for their production, to pharmaceutical compositions containing them, and to their use for the treatment of the conditions set out below. WO 0230871 describes compounds of the type I and WO 0222568 describes compounds of the type II. The compounds also have affinity for the gabapentin binding site and preferably have physiological activities similar to gabapentin particularly with respect to analgesia. 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 glycine, 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 “glycine” (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 glycine. You can also use this procedure to view pending patent applications concerning glycine. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 6. BOOKS ON GLYCINE Overview This chapter provides bibliographic book references relating to glycine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on glycine 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: 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 “glycine” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “glycine” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “glycine” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Pharmacology of Gaba and Glycine Neurotransmission (Handbook of Experimental Pharmacology, 150) by B. E. Alger, et al; ISBN: 3540676163; http://www.amazon.com/exec/obidos/ASIN/3540676163/icongroupinterna
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CHAPTER 7. PERIODICALS AND NEWS ON GLYCINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover glycine.
News Services and Press Releases One of the simplest ways of tracking press releases on glycine 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 “glycine” (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 glycine. 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 “glycine” (or synonyms). 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
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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 “glycine” (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 “glycine” (or synonyms). If you know the name of a company that is relevant to glycine, 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 “glycine” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “glycine” (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 glycine:
Periodicals and News
•
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TUEVP: Initial Experience with Long-Term Follow Up Source: UroTrends. 1(1): 1, 5. Spring 1996. Contact: Available from UroTrends. Circon ACMI, Circon Surgitek, 300 Stillwater Avenue, Stamford, CT 06902-3695. Summary: This article, from a newsletter for urologists, reviews one author's initial experience with long term followup of patients who underwent transurethral electrovaporization of the prostate (TUEVP). The author reviews his experience with a group of 28 patients, and their followup with a minimum time period of 9 months. Preoperatively, all patients received a digital rectal exam, transrectal ultrasound of the prostate, and a serum prostatic specific antigen (PSA) test. The mean preoperative AUA symptoms score was 21, with a mean peak flow of 8.7 ml per second. A Circon ACMI 27 Fr continuous flow resectoscope, glycine irrigation, and a Valleylab Force 2 generator were used for all the TUEVP procedures. In all 28 patients, flexible cystoscopy was done 10, 30, and 90 days after TUEVP to determine the length of time required before reepithelialization of the prostatic fossa was complete. The majority of patients demonstrated significant re-epithelialization after 30 days; complete healing was present by 90 days. Six months postoperatively, the mean AUA symptom score decreased to 5 and the mean peak flow increased to 20 cc per second. The author notes that TUEVP is done within the same anatomical boundaries as transurethral resection (TURP). The goal is to vaporize prostate tissue between the bladder neck and the verumontanum, without perforating the prostate capsule or causing damage to the external sphincter. Since urologists are already trained as resectionists, they need only slightly modify their technique to adapt to the VaporTrode. The author notes that a limiting factor to reaching the maximal effect of TUEVP is the increased electrical resistance encountered with the formation of charred or coagulated tissue. 2 figures. (AA-M).
Academic Periodicals covering Glycine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to glycine. In addition to these sources, you can search for articles covering glycine that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
11
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “glycine” (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 47732 95 329 87 692 48935
HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “glycine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
13
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
14
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
18 Adapted 19
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on glycine 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 glycine. 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 glycine. 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 “glycine”:
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Childhood Immunization http://www.nlm.nih.gov/medlineplus/childhoodimmunization.html Kidney Diseases http://www.nlm.nih.gov/medlineplus/kidneydiseases.html Schizophrenia http://www.nlm.nih.gov/medlineplus/schizophrenia.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to glycine. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to glycine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with glycine. 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 glycine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “glycine” (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 “glycine”. 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 “glycine” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.
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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “glycine” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
21
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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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/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
22
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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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
•
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/
•
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
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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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
•
Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
•
Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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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
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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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
•
New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
•
New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
•
Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
•
Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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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
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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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
•
Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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GLYCINE 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] Ablation: The removal of an organ by surgery. [NIH] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] 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] 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] Acidemia: Increased acidity of blood. [NIH] Acidity: The quality of being acid or sour; containing acid (hydrogen ions). [EU] Acidosis: A pathologic condition resulting from accumulation of acid or depletion of the alkaline reserve (bicarbonate content) in the blood and body tissues, and characterized by an increase in hydrogen ion concentration. [EU] Acoustic: Having to do with sound or hearing. [NIH] Acrylamide: A colorless, odorless, highly water soluble vinyl monomer formed from the hydration of acrylonitrile. It is primarily used in research laboratories for electrophoresis, chromatography, and electron microscopy and in the sewage and wastewater treatment industries. [NIH] Acrylonitrile: A highly poisonous compound used widely in the manufacture of plastics, adhesives and synthetic rubber. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH]
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Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] 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] 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 Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] 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] Adjuvant Therapy: Treatment given after the primary treatment to increase the chances of a cure. Adjuvant therapy may include chemotherapy, radiation therapy, or hormone therapy. [NIH]
Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] 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]
Dictionary 207
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] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Aggravation: An increasing in seriousness or severity; an act or circumstance that intensifies, or makes worse. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] 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] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Alexia: The inability to recognize or comprehend written or printed words. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps
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to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allo: A female hormone. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-Defensins: Defensins found in azurophilic granules of neutrophils and in the secretory granules of intestinal paneth cells. [NIH] Alpha-helix: One of the secondary element of protein. [NIH] Alphavirus: A genus of Togaviridae, also known as Group A arboviruses, serologically related to each other but not to other Togaviridae. The viruses are transmitted by mosquitoes. The type species is the sindbis virus. [NIH] Alprostadil: A potent vasodilator agent that increases peripheral blood flow. It inhibits platelet aggregation and has many other biological effects such as bronchodilation, mediation of inflammation, etc. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Ameliorated: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] 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
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organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acid Substitution: The naturally occurring or experimentally induced replacement of one or more amino acids in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties. [NIH] Amino-terminal: The end of a protein or polypeptide chain that contains a free amino group (-NH2). [NIH] 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] Amoxapine: The N-demethylated derivative of the antipsychotic agent loxapine that works by blocking the reuptake of norepinephrine, serotonin, or both. It also blocks dopamine receptors. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anaemia: A reduction below normal in the number of erythrocytes per cu. mm., in the quantity of haemoglobin, or in the volume of packed red cells per 100 ml. of blood which occurs when the equilibrium between blood loss (through bleeding or destruction) and blood production is disturbed. [EU] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of
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molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analeptic: A drug which acts as a restorative, such as caffeine, amphetamine, pentylenetetrazol, etc. [EU] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anaplasia: Loss of structural differentiation and useful function of neoplastic cells. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] 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
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positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterograde: Moving or extending forward; called also antegrade. [EU] Anthocyanins: Glycosidic pigments in blue, red, and purple flowers and also found as metabolic byproducts in blood and urine. [NIH] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticodon: The sequential set of three nucleotides in transfer RNA that interacts with its complement in messenger RNA, the codon, during translation in the ribosome. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antifungal: Destructive to fungi, or suppressing their reproduction or growth; effective against fungal infections. [EU] Antifungal Agents: Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from fungicides, industrial because they defend against fungi present in human or animal tissues. [NIH] 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
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causes immune complex diseases. [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] 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 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] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Apnea: A transient absence of spontaneous respiration. [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]
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Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] 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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] 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] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Astringent: Causing contraction, usually locally after topical application. [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
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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] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Asymptomatic: Having no signs or symptoms of disease. [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] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] 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] Auditory Cortex: Area of the temporal lobe concerned with hearing. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Avian: A plasmodial infection in birds. [NIH] Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Backcross: A cross between a hybrid and either one of its parents. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Bacteriophage lambda: A temperate inducible phage and type species of the genus lambdalike Phages, in the family Siphoviridae. Its natural host is E. coli K12. Its virion contains linear double-stranded DNA, except for 12 complementary bases at the 5'-termini of the polynucleotide chains. The DNA circularizes on infection. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular
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or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] 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] Benzo(a)pyrene: A potent mutagen and carcinogen. It is a public health concern because of its possible effects on industrial workers, as an environmental pollutant, an as a component of tobacco smoke. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Beta-Defensins: Defensins found mainly in epithelial cells. [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] Bicuculline: Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in
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the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binaural: Used of the two ears functioning together. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biochemical reactions: In living cells, chemical reactions that help sustain life and allow cells to grow. [NIH] Biodegradation: The series of processes by which living organisms degrade pollutant chemicals, organic wastes, pesticides, and implantable materials. [NIH] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids. [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] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [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] 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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Blasts: Immature blood cells. [NIH] 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-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]
Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Hypoxia: Lack of oxygen leading to unconsciousness. [NIH] Brain Infarction: The formation of an area of necrosis in the brain, including the cerebral hemispheres (cerebral infarction), thalami, basal ganglia, brain stem (brain stem infarctions), or cerebellum secondary to an insufficiency of arterial or venous blood flow. [NIH] Brain Ischemia: Localized reduction of blood flow to brain tissue due to arterial obtruction or systemic hypoperfusion. This frequently occurs in conjuction with brain hypoxia. Prolonged ischemia is associated with brain infarction. [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] Breeding: The science or art of changing the constitution of a population of plants or
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animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Caco-2 Cells: Human colonic adenocarcinoma cells that are able to express differentiation features characteristic of mature intestinal cells, such as enterocytes or mucus cells. These cells are valuable in vitro tools for studies related to intestinal cell function and differentiation. [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] 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] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [NIH]
Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates
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are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic. [NIH] 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] 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] Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Castor Bean: Common name for Ricinus communis, a species in the family Euphorbiaceae. It is the source of castor oil. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheters: A small, flexible tube that may be inserted into various parts of the body to inject or remove liquids. [NIH]
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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] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell motility: The ability of a cell to move. [NIH] Cell Physiology: Characteristics and physiological processes of cells from cell division to cell death. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Stimulants: A loosely defined group of drugs that tend to increase behavioral alertness, agitation, or excitation. They work by a variety of mechanisms, but usually not by direct excitation of neurons. The many drugs that have such actions as side effects to their main therapeutic use are not included here. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU]
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Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] 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] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] 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] Chemotherapeutic agent: A drug used to treat cancer. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Chimeras: Organism that contains a mixture of genetically different cells. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]
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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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Climacteric: Physiologic period, characterized by endocrine, somatic, and psychic changes with the termination of ovarian function in the female. It may also accompany the normal diminution of sexual activity in the male. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH]
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Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]
Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [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]
Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [NIH] Cochlear Nucleus: The brain stem nucleus that receives the central input from the cochlear nerve. The cochlear nucleus is located lateral and dorsolateral to the inferior cerebellar peduncles and is functionally divided into dorsal and ventral parts. It is tonotopically organized, performs the first stage of central auditory processing, and projects (directly or indirectly) to higher auditory areas including the superior olivary nuclei, the medial geniculi, the inferior colliculi, and the auditory cortex. [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] Coenzymes: Substances that are necessary for the action or enhancement of action of an enzyme. Many vitamins are coenzymes. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] 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] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the
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high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Colorectal: Having to do with the colon or the rectum. [NIH] 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] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in 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] Complementation: The production of a wild-type phenotype when two different mutations
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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] 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] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Contact dermatitis: Inflammation of the skin with varying degrees of erythema, edema and vesinculation resulting from cutaneous contact with a foreign substance or other exposure. [NIH]
Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
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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] 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 Circulation: The circulation of blood through the coronary vessels of the heart. [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] Corpus: The body of the uterus. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] 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] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]
Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH]
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Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanide: An extremely toxic class of compounds that can be lethal on inhaling of ingesting in minute quantities. [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] Cycloserine: Antibiotic substance produced by Streptomyces garyphalus. It may be used in the treatment of resistant tuberculosis as part of a multi-drug regimen. It has also been used in urinary tract infections. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cystathionine beta-Synthase: A multifunctional pyridoxal phosphate enzyme. In the second stage of cysteine biosynthesis it catalyzes the reaction of homocysteine with serine to form cystathionine with the elimination of water. Deficiency of this enzyme leads to hyperhomocysteinemia and homocystinuria. EC 4.2.1.22. [NIH] Cysteic Acid: Beta-Sulfoalanine. An amino acid with a C-terminal sulfonic acid group which has been isolated from human hair oxidized with permanganate. It occurs normally in the outer part of the sheep's fleece, where the wool is exposed to light and weather. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cysteinyl: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [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]
Cystoscopy: Endoscopic examination, therapy or surgery of the urinary bladder. [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] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH]
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De novo: In cancer, the first occurrence of cancer in the body. [NIH] DEAE-Cellulose: Cellulose derivative used in chromatography, as ion-exchange material, and for various industrial applications. [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] Decompensation: Failure of compensation; cardiac decompensation is marked by dyspnea, venous engorgement, and edema. [EU] Decontamination: The removal of contaminating material, such as radioactive materials, biological materials, or chemical warfare agents, from a person or object. [NIH] Defensins: Family of antimicrobial peptides that have been identified in humans, animals, and plants. They are thought to play a role in host defenses against infections, inflammation, wound repair, and acquired immunity. Based on the disulfide pairing of their characteristic six cysteine residues, they are divided into alpha-defensins and beta-defensins. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH]
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Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule 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] Deoxyuridine: 2'-Deoxyuridine. An antimetabolite that is converted to deoxyuridine triphosphate during DNA synthesis. Laboratory suppression of deoxyuridine is used to diagnose megaloblastic anemias due to vitamin B12 and folate deficiencies. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] 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] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] 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]
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Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diabetic Retinopathy: Retinopathy associated with diabetes mellitus, which may be of the background type, progressively characterized by microaneurysms, interretinal punctuate macular edema, or of the proliferative type, characterized by neovascularization of the retina and optic disk, which may project into the vitreous, proliferation of fibrous tissue, vitreous hemorrhage, and retinal detachment. [NIH] Diacetyl: Carrier of aroma of butter, vinegar, coffee, and other foods. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or highfrequency sound waves. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilator: A device used to stretch or enlarge an opening. [NIH] Dilazep: Coronary vasodilator with some antiarrhythmic activity. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Diploid: Having two sets of chromosomes. [NIH] Dipyridamole: A drug that prevents blood cell clumping and enhances the effectiveness of fluorouracil and other chemotherapeutic agents. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH]
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Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] 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] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [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] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [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] Dormancy: The period when an organism (i. e., a virus or a bacterium) is in the body but not producing any ill effects. [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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH]
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Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Carriers: Substances that facilitate time-controlled delivery, organ-specific targeting, protection, prolonged in vivo function, and decrease of toxicity of drugs. Liposomes, albumin microspheres, soluble synthetic polymers, DNA complexes, protein-drug conjugates, and carrier erythrocytes among others have been employed as biodegradable drug carriers. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Resistance: Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from drug tolerance which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended 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] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyslexia: Partial alexia in which letters but not words may be read, or in which words may be read but not understood. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU]
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Elasticity: Resistance and recovery from distortion of shape. [NIH] Elastin: The protein that gives flexibility to tissues. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [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] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [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] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [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] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions.
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Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [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] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] 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-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] 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] Enflurane: An extremely stable inhalation anesthetic that allows rapid adjustments of anesthesia depth with little change in pulse or respiratory rate. [NIH] Enhancers: Transcriptional element in the virus genome. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [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]
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Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [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] Enzyme Stability: The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat. [NIH] Eosinophil: A polymorphonuclear leucocyte with large eosinophilic granules in its cytoplasm, which plays a role in hypersensitivity reactions. [NIH] Epidermal: Pertaining to or resembling epidermis. Called also epidermic or epidermoid. [EU] Epidermal Growth Factor: A 6 kD polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and epithelial cells. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epidermoid carcinoma: A type of cancer in which the cells are flat and look like fish scales. Also called squamous cell carcinoma. [NIH] Epidermolysis Bullosa: Group of genetically determined disorders characterized by the blistering of skin and mucosae. There are four major forms: acquired, simple, junctional, and dystrophic. Each of the latter three has several varieties. [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] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [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]
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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]
Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry. [NIH] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Erythropoiesis: The production of erythrocytes. [EU] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] 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] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Eukaryote: An organism (or a cell) that carries its genetic material physically constrained within a nuclear membrane, separate from the cytoplasm. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable
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consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [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 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] Excrete: To get rid of waste from the body. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
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]
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Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrillation: A small, local, involuntary contraction of muscle, invisible under the skin, resulting from spontaneous activation of single muscle cells or muscle fibres. [EU] 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] 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] 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 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] Flatus: Gas passed through the rectum. [NIH] Flumazenil: A potent benzodiazepine receptor antagonist. Since it reverses the sedative and
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other actions of benzodiazepines, it has been suggested as an antidote to benzodiazepine overdoses. [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] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [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] Flurothyl: A convulsant primarily used in experimental animals. It was formerly used to induce convulsions as a alternative to electroshock therapy. [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] Fossa: A cavity, depression, or pit. [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] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Freeze-dried: A method used to dry substances, such as food, to make them last longer. The substance is frozen and then dried in a vacuum. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Frostbite: Damage to tissues as the result of low environmental temperatures. [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] Fungicides, Industrial: Chemicals that kill or inhibit the growth of fungi in agricultural
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applications, on wood, plastics, or other materials, in swimming pools, etc. [NIH] Gait: Manner or style of walking. [NIH] Galactosidases: A family of galactoside hydrolases that hydrolyze compounds with an Ogalactosyl linkage. EC 3.2.1.-. [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] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] 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 Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Rearrangement: The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or
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translational levels. [NIH] Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] 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] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germinal Center: The activated center of a lymphoid follicle in secondary lymphoid tissue where B-lymphocytes are stimulated by antigens and helper T cells (T-lymphocytes, helperinducer) are stimulated to generate memory cells. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [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] Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [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] Glutamate: Excitatory neurotransmitter of the brain. [NIH]
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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]
Glutathione Transferase: A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic radicals as well as epoxides and arene oxides to glutathione. Addition takes place at the sulfur atom. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite. EC 2.5.1.18. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Glycylglycine: N-Glycylglycine. The simplest of all peptides. It functions as a gammaglutamyl acceptor. [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]
GP41: 41-kD HIV transmembrane envelope glycoprotein which mediates the fusion of the viral membrane with the membrane of the target cell. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Gramicidin: Antibiotic mixture that is one of the two principle components of tyrothricin from Bacillus brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D, etc., seem to be linear polypeptides. The mixture is used topically for gram-positive organisms. It is toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. [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] Granule: A small pill made from sucrose. [EU] Granulocyte: A type of white blood cell that fights bacterial infection. Neutrophils, eosinophils, and basophils are granulocytes. [NIH]
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Granulocyte-Macrophage Colony-Stimulating Factor: An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages. [NIH] Graphite: An allotropic form of carbon that is used in pencils, as a lubricant, and in matches and explosives. It is obtained by mining and its dust can cause lung irritation. [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 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 Plate: The area between the epiphysis and the diaphysis within which bone growth occurs. [NIH] Guanine: One of the four DNA bases. [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] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] 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] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [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] Haemostasis: The arrest of bleeding, either by the physiological properties of vasoconstriction and coagulation or by surgical means. [EU] Hair follicles: Shafts or openings on the surface of the skin through which hair grows. [NIH] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH]
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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] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [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] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU]
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Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocyte: A liver cell. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Herbicide: A chemical that kills 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] Heterodimers: Zippered pair of nonidentical proteins. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterogenic: Derived from a different source or species. Also called heterogenous. [NIH] Heterogenous: Derived from a different source or species. Also called heterogenic. [NIH] Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Heterozygote: An individual having different alleles at one or more loci in homologous chromosome segments. [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] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] 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] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH]
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Horseradish Peroxidase: An enzyme isolated from horseradish which is able to act as an antigen. It is frequently used as a histochemical tracer for light and electron microscopy. Its antigenicity has permitted its use as a combined antigen and marker in experimental immunology. [NIH] Human papillomavirus: HPV. A virus that causes abnormal tissue growth (warts) and is often associated with some types of cancer. [NIH] Humeral: 1. Of, relating to, or situated in the region of the humerus: brachial. 2. Of or belonging to the shoulder. 3. Of, relating to, or being any of several body parts that are analogous in structure, function, or location to the humerus or shoulder. [EU] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydration: Combining with water. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] 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 Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds. [NIH]
Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., esterases, glycosidases (glycoside hydrolases), lipases, nucleotidases, peptidases (peptide hydrolases), and phosphatases (phosphoric monoester hydrolases). EC 3. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperhomocysteinemia: An inborn error of methionone metabolism which produces an excess of homocysteine in the blood. It is often caused by a deficiency of cystathionine betasynthase and is a risk factor for coronary vascular disease. [NIH] Hyperkeratosis: 1. Hypertrophy of the corneous layer of the skin. 2a. Any of various conditions marked by hyperkeratosis. 2b. A disease of cattle marked by thickening and wringling of the hide and formation of papillary outgrowths on the buccal mucous membranes, often accompanied by watery discharge from eyes and nose, diarrhoea, loss of condition, and abortion of pregnant animals, and now believed to result from ingestion of the chlorinated naphthalene of various lubricating oils. [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
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are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [NIH] Ibotenic Acid: Neurotoxic isoxazole substance found in Amanita muscaria and A. pantherina. It causes motor depression, ataxia, and changes in mood, perceptions and feelings, and is a potent excitatory amino acid agonist. [NIH] Imaging procedures: Methods of producing pictures of areas inside the body. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [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] 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] Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience
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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] 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] Impotence: The inability to perform sexual intercourse. [NIH] Impotent: Unable to have an erection adequate for sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [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] Infant Food: Food processed and manufactured for the nutritional health of children in their first year of life. [NIH] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
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] Influenza: An acute viral infection involving the respiratory tract. It is marked by inflammation of the nasal mucosa, the pharynx, and conjunctiva, and by headache and severe, often generalized, myalgia. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH]
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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] 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] Inotropic: Affecting the force or energy of muscular contractions. [EU] 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] 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] Integrase: An enzyme that inserts DNA into the host genome. It is encoded by the pol gene of retroviruses and also by temperate bacteriophages, the best known being bacteriophage lambda. EC 2.7.7.-. [NIH] Integrase Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of integrase. [NIH] Integrins: A family of transmembrane glycoproteins consisting of noncovalent heterodimers. They interact with a wide variety of ligands including extracellular matrix glycoproteins, complement, and other cells, while their intracellular domains interact with the cytoskeleton. The integrins consist of at least three identified families: the cytoadhesin receptors, the leukocyte adhesion receptors, and the very-late-antigen receptors. Each family contains a common beta-subunit combined with one or more distinct alpha-subunits. These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development, hemostasis, thrombosis, wound healing, immune and nonimmune defense mechanisms, and oncogenic transformation. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons
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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] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH] Intraepithelial: Within the layer of cells that form the surface or lining of an organ. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH] Ion 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] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionophores: Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. [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] Ipsilateral: Having to do with the same side of the body. [NIH] Irrigation: The washing of a body cavity or surface by flowing solution which is inserted
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and then removed. Any drug in the irrigation solution may be absorbed. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Ischemic stroke: A condition in which the blood supply to part of the brain is cut off. Also called "plug-type" strokes. Blocked arteries starve areas of the brain controlling sight, speech, sensation, and movement so that these functions are partially or completely lost. Ischemic stroke is the most common type of stroke, accounting for 80 percent of all strokes. Most ischemic strokes are caused by a blood clot called a thrombus, which blocks blood flow in the arteries feeding the brain, usually the carotid artery in the neck, the major vessel bringing blood to the brain. When it becomes blocked, the risk of stroke is very high. [NIH] 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] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [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 energy levels. [NIH] Isopropyl: A gene mutation inducer. [NIH] Isozymes: The multiple forms of a single enzyme. [NIH] Jealousy: An irrational reaction compounded of grief, loss of self-esteem, enmity against the rival and self criticism. [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] 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] Kidney Cortex: The outer zone of the kidney, beneath the capsule, consisting of kidney glomerulus; kidney tubules, distal; and kidney tubules, proximal. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in
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glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kidney Glomerulus: A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. [NIH] Kinetic: Pertaining to or producing motion. [EU] Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool. [NIH]
Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [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] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]
Learning Disorders: Conditions characterized by a significant discrepancy between an individual's perceived level of intellect and their ability to acquire new language and other cognitive skills. These disorders may result from organic or psychological conditions. Relatively common subtypes include dyslexia, dyscalculia, and dysgraphia. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH]
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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] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [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] 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] Linoleic Acids: Eighteen-carbon essential fatty acids that contain two double bonds. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH] Lipid A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] 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] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives.
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Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of biogenic monoamines in the central nervous system, and affects multiple neurotransmission systems. [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 cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Loxapine: An antipsychotic agent used in schizophrenia. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] 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]
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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] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] 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] 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] 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]
Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mannitol: A diuretic and renal diagnostic aid related to sorbitol. It has little significant
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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] Mass Fragmentography: A microanalytical technique combining mass spectrometry and gas chromatography for the qualitative as well as quantitative determinations of compounds. [NIH]
Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrilysin: The smallest member of the matrix metalloproteinases. It plays a role in tumor progression. EC 3.4.24.23. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] 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] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH]
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Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [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]
Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesenchymal: Refers to cells that develop into connective tissue, blood vessels, and lymphatic tissue. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methicillin Resistance: Non-susceptibility of a microbe to the action of methicillin, a semisynthetic penicillin derivative. [NIH] 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] Micelle: A colloid particle formed by an aggregation of small molecules. [EU]
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Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microspheres: Small uniformly-sized spherical particles frequently radioisotopes or various reagents acting as tags or markers. [NIH]
labeled
with
Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular 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] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH]
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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] Mononuclear: A cell with one nucleus. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [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 nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Mucinous: Containing or resembling mucin, the main compound in mucus. [NIH] Mucolytic: Destroying or dissolving mucin; an agent that so acts : a mucopolysaccharide or glycoprotein, the chief constituent of mucus. [EU] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [NIH] Muramidase: A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-betalinkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC 3.2.1.17. [NIH]
Muscimol: Neurotoxic isoxazole isolated from Amanita muscaria and A. phalloides and also obtained by decarboxylation of ibotenic acid. It is a potent agonist at GABA-A receptors and is used mainly as an experimental tool in animal and tissue studies. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [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]
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Muscle Spasticity: Strongly marked hypertonicity of muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutate: To change the genetic material of a cell. Then changes (mutations) can be harmful, beneficial, or have no effect. [NIH] Myalgia: Pain in a muscle or muscles. [EU] 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] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myristate: Pharmacological activator of protein kinase C. [NIH] Nadir: The lowest point; point of greatest adversity or despair. [EU] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit.
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Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nerve Regeneration: Renewal or physiological repair of damaged nerve tissue. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [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] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuraminidase: An enzyme that catalyzes the hydrolysis of alpha-2,3, alpha-2,6-, and alpha-2,8-glycosidic linkages (at a decreasing rate, respectively) of terminal sialic residues in oligosaccharides, glycoproteins, glycolipids, colominic acid, and synthetic substrate. (From Enzyme Nomenclature, 1992) EC 3.2.1.18. [NIH] 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
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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] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] 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] Nickel: A trace element with the atomic symbol Ni, atomic number 28, and atomic weight 58.69. It is a cofactor of the enzyme urease. [NIH] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Ninhydrin: 2,2-Dihydroxy-1H-indene-1,3-(2H)-dione. Reagent toxic to skin and mucus membranes. It is used in chemical assay for peptide bonds, i.e., protein determinations and has radiosensitizing properties. [NIH]
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Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [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] Nitrosamines: A class of compounds that contain a -NH2 and a -NO radical. Many members of this group have carcinogenic and mutagenic properties. [NIH] Nitrosation: Conversion into nitroso compounds. An example is the reaction of nitrites with amino compounds to form carcinogenic N-nitrosamines. [NIH] Nonmalignant: Not cancerous. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nosocomial: Pertaining to or originating in the hospital, said of an infection not present or incubating prior to admittance to the hospital, but generally occurring 72 hours after admittance; the term is usually used to refer to patient disease, but hospital personnel may also acquire nosocomial infection. [EU] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the
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next. [NIH] Nucleocapsid: A protein-nucleic acid complex which forms part or all of a virion. It consists of a capsid plus enclosed nucleic acid. Depending on the virus, the nucleocapsid may correspond to a naked core or be surrounded by a membranous envelope. [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] Nucleoproteins: Proteins conjugated with nucleic acids. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Olfactory Nerve: The 1st cranial nerve. The olfactory nerve conveys the sense of smell. It is formed by the axons of olfactory receptor neurons which project from the olfactory epithelium (in the nasal epithelium) to the olfactory bulb. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [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] 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] 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] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH]
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Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] 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] Orofacial: Of or relating to the mouth and face. [EU] Orthostatic: Pertaining to or caused by standing erect. [EU] Osmolarity: The concentration of osmotically active particles expressed in terms of osmoles of solute per litre of solution. [EU] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteoblasts: Bone-forming cells which secrete an extracellular matrix. Hydroxyapatite crystals are then deposited into the matrix to form bone. [NIH] Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by osteoblasts and found primarily in bone. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gammacarboxyglutamic acid (GLA), which, in the presence of calcium, promotes binding to hydroxyapatite and subsequent accumulation in bone matrix. [NIH] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH] Osteogenesis Imperfecta: A collagen disorder resulting from defective biosynthesis of type I collagen and characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. There are four major types, I-IV. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The
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ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] 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]
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 metabolism. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygenase: Enzyme which breaks down heme, the iron-containing oxygen-carrying constituent of the red blood cells. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] 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] 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] 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] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used
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in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] 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] Paradoxical: Occurring at variance with the normal rule. [EU] Paralysis: Loss of ability to move all or part of the body. [NIH] Paramyxovirus: A genus of the family Paramyxoviridae (subfamily Paramyxovirinae) where all the virions have both hemagglutinin and neuraminidase activities and encode a C protein. Human parainfluenza virus 1 is the type species. [NIH] Paranoia: A psychotic disorder marked by persistent delusions of persecution or delusional jealousy and behaviour like that of the paranoid personality, such as suspiciousness, mistrust, and combativeness. It differs from paranoid schizophrenia, in which hallucinations or formal thought disorder are present, in that the delusions are logically consistent and that there are no other psychotic features. The designation in DSM III-R is delusional (paranoid) disorders, with five types : persecutory, jealous, erotomanic, somatic, and grandiose. [EU] 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] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]
Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Peak flow: The maximum amount of air breathed out; the power needed to produce this amount. [EU] Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH]
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Penicillin: An antibiotic drug used to treat infection. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peptide Mapping: Analysis of peptides generated from the digestion of a protein by a specific protease for the purpose of indentifing the protein or to look for polymorphisms. [NIH]
Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Perch: A common name for fish belonging to the order Perciformes with many genera and species. [NIH] Perennial: Lasting through the year of for several years. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] 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 Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peripheral vision: Side vision; ability to see objects and movement outside of the direct line of vision. [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] Perspiration: Sweating; the functional secretion of sweat. [EU]
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Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petechiae: Pinpoint, unraised, round red spots under the skin caused by bleeding. [NIH] P-Glycoprotein: A 170 kD transmembrane glycoprotein from the superfamily of ABC transporters. It serves as an ATP-dependent efflux pump for a variety of chemicals, including many antineoplastic agents. Overexpression of this glycoprotein is associated with multidrug resistance. [NIH] Phallic: Pertaining to the phallus, or penis. [EU] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] 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] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phencyclidine: A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to ketamine in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (receptors, N-methyl-Daspartate). As a drug of abuse, it is known as PCP and Angel Dust. [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] Phentolamine: A nonselective alpha-adrenergic antagonist. It is used in the treatment of hypertension and hypertensive emergencies, pheochromocytoma, vasospasm of Raynaud's disease and frostbite, clonidine withdrawal syndrome, impotence, and peripheral vascular disease. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [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] 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] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH]
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Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Phytotoxin: A substance which is toxic for plants. [NIH] Picrotoxin: A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GABA-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. [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] Plant Viruses: Viruses parasitic on plants higher than bacteria. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]
Pleated: Particular three-dimensional pattern of amyloidoses. [NIH]
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Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [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] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyarthritis: An inflammation of several joints together. [EU] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] 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] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [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] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH]
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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] Postural: Pertaining to posture or position. [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] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [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] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Preoperative: Preceding an operation. [EU] 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] Primary Biliary Cirrhosis: A chronic liver disease. Slowly destroys the bile ducts in the liver. This prevents release of bile. Long-term irritation of the liver may cause scarring and cirrhosis in later stages of the disease. [NIH] Primary tumor: The original tumor. [NIH] Prion: Small proteinaceous infectious particles that resist inactivation by procedures
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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] Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal ends of the three polypeptide chains. Protocollagen, a precursor of procollagen consists of procollagen peptide chains in which proline and lysine have not yet been hydroxylated. [NIH] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progeny: The offspring produced in any generation. [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] Prone: Having the front portion of the body downwards. [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] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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]
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Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [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 Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [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-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] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. [NIH]
Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] 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] Protozoan: 1. Any individual of the protozoa; protozoon. 2. Of or pertaining to the protozoa; protozoal. [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]
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Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotomimetic: Psychosis miming. [NIH] 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 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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] Pyruvate 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]
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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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radioisotope: An unstable element that releases radiation as it breaks down. Radioisotopes can be used in imaging tests or as a treatment for cancer. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Raffinose: A trisaccharide occurring in Australian manna (from Eucalyptus spp, Myrtaceae) and in cottonseed meal. [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] Rationalize: To attribute one's actions to rational and creditable motives without adequate analysis of the true and unconscious motives. [NIH] 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] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH]
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Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Reconstitution: 1. A type of regeneration in which a new organ forms by the rearrangement of tissues rather than from new formation at an injured surface. 2. The restoration to original form of a substance previously altered for preservation and storage, as the restoration to a liquid state of blood serum or plasma that has been dried and stored. [EU] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] 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] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reperfusion: Restoration of blood supply to tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. It is primarily a procedure for treating infarction or other ischemia, by enabling viable ischemic tissue to recover, thus limiting further necrosis. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing reperfusion injury. [NIH] Reperfusion Injury: Functional, metabolic, or structural changes, including necrosis, in ischemic tissues thought to result from reperfusion to ischemic areas of the tissue. The most common instance is myocardial reperfusion injury. [NIH] Resected: Surgical removal of part of an organ. [NIH] Resection: Removal of tissue or part or all of an organ by surgery. [NIH]
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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] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [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] Retrograde: 1. Moving backward or against the usual direction of flow. 2. Degenerating, deteriorating, or catabolic. [EU] Retrospective: Looking back at events that have already taken place. [NIH] 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] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series
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of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Ricin: A protein phytotoxin from the seeds of Ricinus communis, the castor oil plant. It agglutinates cells, is proteolytic, and causes lethal inflammation and hemorrhage if taken internally. [NIH] Rickettsiae: One of a group of obligate intracellular parasitic microorganisms, once regarded as intermediate in their properties between bacteria and viruses but now classified as bacteria in the order Rickettsiales, which includes 17 genera and 3 families: Rickettsiace. [NIH]
Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risk patient: Patient who is at risk, because of his/her behaviour or because of the type of person he/she is. [EU] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport. [NIH]
Salicylic: A tuberculosis drug. [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] Sarcosine: Methylamino-acetic acid. [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] Sclerae: A circular furrow between the sclerocorneal junction and the iris. [NIH] Scleroproteins: Simple proteins characterized by their insolubility and fibrous structure. Within the body, they perform a supportive or protective function. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical
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structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [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] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedimentation: The act of causing the deposit of sediment, especially by the use of a centrifugal machine. [EU] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] 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] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] 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] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH]
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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] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Serum Albumin: A major plasma protein that serves in maintaining the plasma colloidal osmotic pressure and transporting large organic anions. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
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] Sindbis Virus: The type species of alphavirus normally transmitted to birds by Culex mosquitoes in Egypt, South Africa, India, Malaya, the Philippines, and Australia. It may be associated with fever in humans. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skin graft: Skin that is moved from one part of the body to another. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or absence of respiratory effort. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smallpox: A generalized virus infection with a vesicular rash. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [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]
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Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions. [NIH] Sodium Dodecyl Sulfate: An anionic surfactant, usually a mixture of sodium alkyl sulfates, mainly the lauryl; lowers surface tension of aqueous solutions; used as fat emulsifier, wetting agent, detergent in cosmetics, pharmaceuticals and toothpastes; also as research tool in protein biochemistry. [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] 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] Sonogram: A computer picture of areas inside the body created by bouncing sound waves off organs and other tissues. Also called ultrasonogram or ultrasound. [NIH] Sorbitol: A polyhydric alcohol with about half the sweetness of sucrose. Sorbitol occurs naturally and is also produced synthetically from glucose. It was formerly used as a diuretic and may still be used as a laxative and in irrigating solutions for some surgical procedures. It is also used in many manufacturing processes, as a pharmaceutical aid, and in several research applications. [NIH] Sound Localization: Ability to determine the specific location of a sound source. [NIH] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] 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] Spasmodic: Of the nature of a spasm. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectroscopic: The recognition of elements through their emission spectra. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Perception: The process whereby an utterance is decoded into a representation in terms of linguistic units (sequences of phonetic segments which combine to form lexical and
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grammatical morphemes). [NIH] 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] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] 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] Spina bifida: A defect in development of the vertebral column in which there is a central deficiency of the vertebral lamina. [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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Spores: The reproductive elements of lower organisms, such as protozoa, fungi, and cryptogamic plants. [NIH] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Squamous cells: Flat cells that look like fish scales under a microscope. These cells cover internal and external surfaces of the body. [NIH] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Steady state: Dynamic equilibrium. [EU] Steel: A tough, malleable, iron-based alloy containing up to, but no more than, two percent carbon and often other metals. It is used in medicine and dentistry in implants and instrumentation. [NIH] Stellate: Star shaped. [NIH] Sterile: Unable to produce children. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this 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]
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Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stomatitis: Inflammation of the oral mucosa, due to local or systemic factors which may involve the buccal and labial mucosa, palate, tongue, floor of the mouth, and the gingivae. [EU]
Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or 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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [NIH] Strychnine: An alkaloid found in the seeds of nux vomica. It is a competitive antagonist at glycine receptors and thus a convulsant. It has been used as an analeptic, in the treatment of nonketotic hyperglycinemia and sleep apnea, and as a rat poison. [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] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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] Sulfates: Inorganic salts of sulfuric acid. [NIH] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S,
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atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Sulfur Compounds: Inorganic or organic compounds that contain sulfur as an integral part of the molecule. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. [NIH] 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] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] 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]
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Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Taurine: 2-Aminoethanesulfonic acid. A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Tellurium: Tellurium. An element that is a member of the chalcogen family. It has the atomic symbol Te, atomic number 52, and atomic weight 127.60. It has been used as a coloring agent and in the manufacture of electrical equipment. Exposure may cause nausea, vomiting, and CNS depression. [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] Tendon: A discrete band of connective tissue mainly composed of parallel bundles of collagenous fibers by which muscles are attached, or two muscles bellies joined. [NIH] 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] Tetanic: Having the characteristics of, or relating to tetanus. [NIH] Tetanus: A disease caused by tetanospasmin, a powerful protein toxin produced by Clostridium tetani. Tetanus usually occurs after an acute injury, such as a puncture wound or laceration. Generalized tetanus, the most common form, is characterized by tetanic muscular contractions and hyperreflexia. Localized tetanus presents itself as a mild condition with manifestations restricted to muscles near the wound. It may progress to the generalized form. [NIH] 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]
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]
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Thermal: Pertaining to or characterized by heat. [EU] Thioredoxin: A hydrogen-carrying protein that participates in a variety of biochemical reactions including ribonucleotide reduction. Thioredoxin is oxidized from a dithiol to a disulfide during ribonucleotide reduction. The disulfide form is then reduced by NADPH in a reaction catalyzed by thioredoxin reductase. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] 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]
Thromboses: The formation or presence of a blood clot within a blood vessel during life. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] Tissue Extracts: Preparations made from animal tissues or organs; they usually contain many components, any one of which may be pharmacologically or physiologically active; extracts may contain specific, but uncharacterized factors or proteins with specific actions. [NIH]
Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU]
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Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [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] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tracer: A substance (such as a radioisotope) used in imaging procedures. [NIH] Traction: The act of pulling. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] 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] Transfusion: The infusion of components of blood or whole blood into the bloodstream. The blood may be donated from another person, or it may have been taken from the person earlier and stored until needed. [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]
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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] Transrectal ultrasound: A procedure used to examine the prostate. An instrument is inserted into the rectum, and sound waves bounce off the prostate. These sound waves create echoes, which a computer uses to create a picture called a sonogram. [NIH] Transurethral: Performed through the urethra. [EU] Transurethral resection: Surgery performed with a special instrument inserted through the urethra. Also called TUR. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Triglyceride: A lipid carried through the blood stream to tissues. Most of the body's fat tissue is in the form of triglycerides, stored for use as energy. Triglycerides are obtained primarily from fat in foods. [NIH] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Tunica: A rather vague term to denote the lining coat of hollow organs, tubes, or cavities. [NIH]
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]
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Tyrothricin: A polypeptide antibiotic mixture obtained from Bacillus brevis. It consists of a mixture of three tyrocidines (60%) and several gramicidins (20%) and is very toxic to blood, liver, kidneys, meninges, and the olfactory apparatus. It is used topically. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uncoupling Agents: Chemical agents that uncouple oxidation from phosphorylation in the metabolic cycle so that ATP synthesis does not occur. Included here are those ionophores that disrupt electron transfer by short-circuiting the proton gradient across mitochondrial membranes. [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] Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urinary tract infection: An illness caused by harmful bacteria growing in the urinary tract. [NIH]
Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccination: Administration of vaccines to stimulate the host's immune response. This includes any preparation intended for active immunological prophylaxis. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]
Vaccinia: The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]
Dictionary 291
Variola: A generalized virus infection with a vesicular rash. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venter: Belly. [NIH] 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] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vial: A small bottle. [EU] Vinblastine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. It is a mitotic inhibitor. [NIH]
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Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Proteins: Proteins found in any species of virus. [NIH] 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] 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] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitreous Hemorrhage: Hemorrhage into the vitreous body. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]
Vomeronasal Organ: A specialized part of the olfactory system located anteriorly in the nasal cavity within the nasal septum. Chemosensitive cells of the vomeronasal organ project via the vomeronasal nerve to the accessory olfactory bulb. The primary function of this organ appears to be in sensing pheromones which regulate reproductive and other social behaviors. While the structure has been thought absent in higher primate adults, data now suggests it may be present in adult humans. [NIH] Vomica: The profuse and sudden expectoration of pus and putrescent matter. An abnormal cavity in an organ especially in the lung, caused by suppuration and the breaking down of tissue. [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]
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Warts: Benign epidermal proliferations or tumors; some are viral in origin. [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]
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Wound Healing: Restoration of integrity to traumatized tissue. [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] 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] Zebrafish: A species of North American fishes of the family Cyprinidae. They are used in embryological studies and to study the effects of certain chemicals on development. [NIH] Zinc Oxide: A mild astringent and topical protectant with some antiseptic action. It is also used in bandages, pastes, ointments, dental cements, and as a sunblock. [NIH] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
295
INDEX 3 3-dimensional, 16, 205, 273 A Abdomen, 205, 217, 235, 250, 254, 267, 268, 284, 287 Abdominal, 205, 206, 230, 266, 268 Ablation, 12, 105, 108, 205 Abortion, 205, 246 Acceptor, 56, 205, 242, 253, 266, 288 Acetylcholine, 6, 47, 87, 205, 222, 262, 263 Acetylcysteine, 79, 205 Acidemia, 94, 205 Acidity, 205 Acidosis, 64, 205, 275 Acoustic, 12, 124, 205 Acrylamide, 149, 205 Acrylonitrile, 205 Actin, 141, 205, 259, 260 Acute renal, 4, 130, 205, 244 Acyl, 154, 206 Adaptability, 206, 220 Adaptation, 27, 46, 135, 206, 259, 262, 270 Adenine, 56, 148, 206, 275 Adenocarcinoma, 171, 206, 218, 245 Adenosine, 147, 206, 214, 218, 269, 286 Adenosine Triphosphate, 147, 206, 214, 269 Adhesives, 143, 205, 206 Adipocytes, 206, 252 Adjustment, 162, 206 Adjuvant, 120, 206, 240 Adjuvant Therapy, 120, 206 Adrenal Cortex, 206, 226, 236 Adrenergic, 206, 212, 231, 235, 269, 285 Adverse Effect, 206, 281 Aerobic, 206, 258, 266 Aerobic Metabolism, 206, 266 Aerobic Respiration, 206, 266 Aerosol, 156, 206 Afferent, 38, 207, 252, 272, 280 Affinity, 36, 51, 59, 69, 74, 79, 150, 167, 176, 177, 207, 214, 281 Age Groups, 14, 207 Aged, 80 and Over, 207 Aggravation, 162, 207 Agonist, 7, 10, 14, 32, 36, 37, 47, 65, 73, 93, 98, 126, 148, 164, 165, 167, 175, 207, 231, 247, 259
Airway, 39, 156, 207, 281 Akathisia, 207, 212 Alanine, 46, 56, 60, 64, 69, 75, 83, 101, 109, 132, 138, 142, 143, 159, 168, 172, 173, 207 Albumin, 3, 138, 157, 168, 169, 207, 232, 270 Alcohol Dehydrogenase, 93, 207 Alertness, 207, 218, 220 Alexia, 207, 232 Algorithms, 207, 216 Alimentary, 175, 208 Alkaline, 150, 163, 171, 205, 208, 209, 218, 266 Alkaline Phosphatase, 150, 208 Alkaloid, 175, 208, 215, 218, 223, 266, 284, 286 Alleles, 55, 124, 208, 245 Allergen, 208, 229, 280 Allo, 50, 208, 243 Allylamine, 26, 208, 209 Alpha-1, 54, 208 Alpha-Defensins, 208, 228 Alpha-helix, 95, 208, 251 Alphavirus, 34, 208, 281 Alprostadil, 145, 165, 208 Alternative medicine, 182, 208 Alternative Splicing, 84, 208, 274 Aluminum, 139, 208 Ameliorated, 139, 208 Ameliorating, 139, 208 Amine, 150, 163, 208, 216, 245 Amino Acid Sequence, 36, 42, 140, 209, 211, 237, 241, 273 Amino Acid Substitution, 51, 147, 209 Amino-terminal, 65, 209, 273 Ammonia, 23, 72, 109, 139, 208, 209, 242, 285, 290 Amoxapine, 77, 209 Amphetamine, 37, 209, 210, 230 Amplification, 118, 163, 209 Ampulla, 209, 221, 234 Amygdala, 209, 215, 253, 280 Amyloid, 82, 209 Anaemia, 101, 209, 256 Anaerobic, 58, 61, 209 Anaesthesia, 85, 108, 210, 248 Anal, 149, 210, 238 Analeptic, 210, 284
296
Glycine
Analgesics, 171, 210 Analog, 41, 61, 210, 239 Analogous, 210, 246, 288 Analytes, 163, 210 Anaphylatoxins, 210, 224 Anaplasia, 210 Anatomical, 38, 43, 55, 183, 210, 221, 233, 248, 279 Anemia, 27, 210, 239, 255 Anesthesia, 5, 7, 15, 44, 97, 126, 207, 210, 234, 251 Anesthetics, 7, 15, 36, 37, 44, 126, 146, 210, 215, 235 Angina, 169, 175, 210 Angina Pectoris, 175, 210 Angiogenesis, 210, 256 Animal model, 17, 19, 23, 32, 35, 37, 42, 210 Anionic, 25, 210, 282 Anions, 207, 210, 250, 281 Ankle, 54, 211 Annealing, 211, 271 Antagonism, 7, 59, 83, 96, 211, 218, 286 Anterograde, 39, 211 Anthocyanins, 118, 159, 160, 211 Antiangiogenic, 50, 211 Antiarrhythmic, 211, 230 Antibacterial, 49, 211, 259, 282 Antibiotic, 45, 48, 57, 211, 218, 227, 242, 268, 282, 290 Antibodies, 59, 84, 140, 156, 157, 158, 161, 163, 166, 167, 170, 211, 236, 243, 244, 247, 255, 259, 270 Antibody, 67, 163, 170, 207, 211, 224, 236, 243, 245, 247, 248, 256, 259, 276, 280, 282 Anticoagulant, 75, 211, 273 Anticodon, 62, 65, 211 Anticonvulsant, 117, 211, 279 Antidote, 211, 239, 270 Antiemetic, 211, 212 Antifungal, 113, 211 Antifungal Agents, 113, 211 Antigen, 43, 80, 81, 141, 183, 207, 211, 224, 245, 246, 247, 248, 249, 256, 280 Antigen-Antibody Complex, 211, 224 Antimetabolite, 212, 229, 239 Antimicrobial, 31, 49, 212, 228, 229 Antineoplastic, 40, 154, 212, 239, 241, 266, 269 Antineoplastic Agents, 212, 269 Antioxidant, 21, 128, 212, 266 Antipsychotic, 30, 209, 212, 254, 262, 279
Antiseptic, 212, 293 Antiviral, 98, 147, 154, 205, 212, 249, 268 Anus, 171, 210, 212, 224, 277 Anxiety, 51, 145, 165, 169, 176, 207, 212, 266 Anxiety Disorders, 212, 266 Apnea, 39, 212 Aponeurosis, 212, 240 Apoptosis, 5, 23, 29, 42, 118, 121, 212, 227 Applicability, 47, 212 Aqueous, 140, 142, 150, 152, 155, 163, 170, 171, 213, 227, 233, 252, 282 Arachidonate 12-Lipoxygenase, 213, 254 Arachidonate 15-Lipoxygenase, 213, 254 Arachidonate Lipoxygenases, 213, 254 Arterial, 26, 145, 161, 165, 208, 213, 217, 246, 274, 286 Arteries, 145, 165, 213, 217, 219, 226, 251, 254, 257, 260 Arterioles, 213, 217, 218, 258, 260 Arteriolosclerosis, 213 Arteriosclerosis, 26, 142, 213, 260 Artery, 142, 213, 217, 219, 226, 251, 260, 275, 277, 286, 291 Arthroscopy, 91, 107, 213 Ascites, 64, 213 Aspartate, 9, 14, 28, 37, 50, 58, 60, 62, 64, 65, 75, 79, 90, 121, 148, 158, 167, 175, 213, 251, 269 Aspartic, 26, 43, 58, 68, 70, 81, 82, 83, 100, 105, 130, 153, 172, 173, 213 Aspartic Acid, 26, 43, 58, 68, 70, 81, 82, 83, 100, 105, 130, 153, 172, 173, 213 Assay, 17, 28, 56, 76, 82, 83, 150, 213, 247, 262, 289 Asthenia, 175, 213 Astringent, 139, 213, 293 Astrocytes, 213, 214, 258 Astrocytoma, 106, 214 Asymptomatic, 58, 214 Atmospheric Pressure, 80, 94, 214 ATP, 5, 17, 28, 56, 61, 103, 214, 226, 231, 241, 242, 250, 269, 274, 290 Atrophy, 214, 262 Attenuated, 31, 88, 214, 290 Atypical, 38, 214, 279 Auditory, 6, 8, 12, 13, 175, 214, 223, 236, 244, 272 Auditory Cortex, 214, 223 Autonomic, 205, 212, 214, 263, 268 Autoradiography, 6, 214 Avian, 44, 214
297
Axonal, 38, 214 Axons, 39, 214, 229, 250, 264, 265, 278 B Backcross, 28, 214 Bacterial Infections, 49, 214 Bacterial Physiology, 206, 214 Bactericidal, 31, 153, 214, 236 Bacteriophage, 214, 249, 288 Bacteriophage lambda, 214, 249 Bacterium, 136, 214, 225, 231, 244 Barbiturate, 73, 215 Basal Ganglia, 35, 167, 212, 215, 217, 222, 240, 247, 253, 264 Basal Ganglia Diseases, 215, 222, 247 Base Sequence, 215, 239, 241 Basement Membrane, 215, 237 Basophils, 215, 242, 253 Benign, 131, 213, 215, 240, 244, 261, 267, 293 Benzene, 215, 251 Benzo(a)pyrene, 85, 215 Benzodiazepines, 215, 239 Beta-Defensins, 215, 228 Beta-pleated, 209, 215 Beta-sheet, 57, 215 Bicuculline, 7, 70, 215 Bilateral, 215, 278 Bile, 70, 87, 106, 215, 216, 254, 272, 283, 286 Bile Acids, 87, 215, 283, 286 Bile Acids and Salts, 215 Bile duct, 216, 272 Biliary, 216, 221 Bilirubin, 207, 216 Binaural, 13, 216 Binding Sites, 15, 52, 216 Bioavailability, 71, 80, 125, 216 Biochemical reactions, 216, 287 Biodegradation, 50, 216 Biogenic Monoamines, 216, 254 Biological therapy, 216, 243 Biological Transport, 216, 230 Bioluminescence, 216, 254 Biosynthesis, 32, 59, 61, 62, 90, 216, 227, 249, 265, 280 Biotechnology, 57, 66, 99, 126, 127, 129, 147, 150, 182, 189, 216 Biotransformation, 216 Bismuth, 67, 154, 155, 216 Bladder, 183, 216, 227, 261, 273, 290 Blastocyst, 216, 225, 270 Blasts, 152, 217
Blood Coagulation, 138, 161, 168, 217, 218, 287 Blood Coagulation Factors, 217 Blood Glucose, 217, 244, 249 Blood Platelets, 217, 281 Blood pressure, 217, 219, 221, 246, 247, 258, 268, 281 Blood-Brain Barrier, 217, 253 Blot, 55, 217 Body Fluids, 217, 232, 281 Bone Marrow, 28, 215, 217, 227, 243, 247, 254, 255, 259, 282 Bone Marrow Cells, 217, 243 Bowel, 210, 217, 250, 252, 261, 284 Brachial, 217, 246 Bradykinin, 217, 263, 270 Brain Hypoxia, 217 Brain Infarction, 217 Brain Ischemia, 7, 217 Brain Stem, 6, 217, 221, 223 Breeding, 141, 160, 217 Broad-spectrum, 32, 155, 218, 252 Buccal, 218, 246, 254, 284 Butyric Acid, 21, 73, 167, 218 C Caco-2 Cells, 105, 218 Caffeine, 210, 218, 275 Calcification, 213, 218 Calcium, 13, 14, 50, 51, 64, 82, 118, 138, 148, 168, 172, 218, 224, 256, 260, 265, 267, 274 Calcium Channels, 218, 267 Camptothecin, 118, 218 Capillary, 46, 217, 218, 241, 291 Capsid, 147, 166, 218, 264, 292 Capsules, 218, 231, 240, 241 Carbohydrate, 130, 141, 218, 242, 271 Carbon Dioxide, 219, 228, 238, 240, 270, 275, 278, 290, 291 Carboxy, 219 Carboxylic Acids, 150, 219 Carcinogen, 48, 215, 219 Carcinogenesis, 47, 96, 219 Carcinogenic, 215, 219, 249, 263, 264, 273, 283 Carcinoma, 95, 152, 161, 170, 171, 219 Cardiac, 4, 17, 175, 208, 211, 218, 219, 228, 233, 235, 237, 260, 283 Cardiovascular, 16, 24, 142, 145, 165, 175, 209, 218, 219, 281 Cardiovascular disease, 16, 24, 142, 145, 165, 219
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Glycine
Carnitine, 175, 219 Carotene, 219, 278 Carotid Arteries, 130, 219 Carrier Proteins, 219, 270 Case report, 72, 91, 219 Castor Bean, 148, 219 Castor Oil, 219, 279 Catabolism, 22, 64, 219 Catalytic Domain, 89, 219 Catecholamine, 219, 231 Catheters, 163, 219 Cations, 220, 250 Caudal, 220, 230, 247, 264, 271 Caudate Nucleus, 215, 220, 264 Cell Adhesion, 81, 125, 220, 249 Cell Death, 14, 31, 32, 35, 43, 170, 212, 220, 261 Cell Differentiation, 29, 220 Cell Division, 214, 220, 243, 256, 258, 270, 273, 280 Cell membrane, 13, 34, 106, 216, 218, 219, 220, 229, 240, 250, 256, 269, 272, 292 Cell motility, 27, 220 Cell Physiology, 31, 112, 130, 220 Cell proliferation, 30, 48, 51, 213, 220 Cell Respiration, 206, 220, 258, 266, 278 Cell Survival, 220, 243 Cellulose, 220, 228, 270 Central Nervous System Stimulants, 146, 220 Centrifugation, 153, 220, 285 Ceramide, 95, 220 Cerebellar, 8, 62, 220, 221, 223, 277, 289 Cerebellar Diseases, 221, 289 Cerebellum, 8, 217, 220, 221, 271, 277 Cerebral Cortex, 221, 236, 238, 261 Cerebral hemispheres, 215, 217, 221, 286 Cerebrovascular, 215, 219, 221 Cerebrum, 221, 286 Cervical, 170, 171, 221 Cervix, 205, 221 Character, 210, 221, 228 Chemical Warfare, 221, 228 Chemical Warfare Agents, 221, 228 Chemoreceptor, 212, 221 Chemotactic Factors, 221, 224 Chemotherapeutic agent, 40, 221, 230 Chemotherapy, 40, 118, 206, 221 Chimeras, 45, 221 Chin, 221, 257 Cholestasis, 106, 221
Cholesterol, 127, 215, 222, 226, 253, 254, 283 Choline, 8, 25, 29, 106, 222 Cholinergic, 39, 212, 222, 280 Chondrocytes, 222, 238 Chorea, 212, 222 Chorioretinitis, 222, 278 Choroid, 222, 278 Chromatin, 20, 212, 222, 283 Chromosomal, 28, 73, 209, 222, 245 Chromosome, 63, 73, 95, 222, 225, 243, 245, 253, 280 Chronic, 19, 62, 69, 70, 118, 161, 175, 222, 234, 248, 251, 252, 272, 284, 292 Chronic renal, 70, 222 Cirrhosis, 161, 222, 244, 272 CIS, 21, 75, 97, 222, 278 Clamp, 8, 12, 13, 14, 18, 33, 45, 49, 222 Clear cell carcinoma, 222, 229 Cleave, 55, 222 Climacteric, 112, 121, 222 Clinical Medicine, 92, 222, 272 Clinical trial, 4, 53, 54, 189, 222, 225, 227, 232, 274, 276 Clone, 20, 24, 42, 223 Cloning, 29, 41, 42, 59, 62, 112, 160, 216, 223, 253 Coca, 223 Cocaine, 51, 223 Cochlea, 223 Cochlear, 7, 12, 122, 124, 223 Cochlear Nerve, 223 Cochlear Nucleus, 122, 124, 223 Codon, 18, 61, 109, 211, 223, 241 Coenzymes, 20, 223, 262 Cofactor, 138, 168, 223, 262, 274, 287 Cognition, 167, 223, 262 Colchicine, 223, 289 Colloidal, 207, 224, 233, 281 Colon, 22, 47, 52, 68, 78, 84, 86, 92, 123, 224, 252 Colorectal, 47, 51, 76, 224 Colorectal Cancer, 48, 51, 224 Communication Disorders, 13, 188, 224 Communis, 219, 224, 279 Complement, 41, 141, 210, 211, 224, 241, 249, 255, 270, 280 Complementary and alternative medicine, 117, 133, 224 Complementary medicine, 117, 224 Complementation, 24, 151, 224 Computational Biology, 189, 225
299
Conception, 205, 225, 238 Concomitant, 40, 74, 225 Cone, 225, 269 Congestion, 212, 225, 236 Conjugated, 106, 172, 215, 225, 227, 263, 264 Conjugation, 21, 88, 93, 118, 172, 216, 225 Conjunctiva, 225, 248, 289 Connective Tissue, 217, 223, 225, 229, 238, 240, 252, 254, 257, 286 Consciousness, 210, 225, 228, 231, 275 Constipation, 212, 225 Constitutional, 225, 278 Constriction, 145, 165, 225, 251, 291 Contact dermatitis, 68, 225 Contamination, 153, 158, 161, 225 Contraindications, ii, 225 Contralateral, 13, 225, 257, 265, 277 Controlled study, 94, 225 Convulsions, 211, 215, 226, 239 Convulsive, 146, 226, 233 Coordination, 221, 226 Coronary, 142, 210, 219, 226, 230, 246, 257, 260 Coronary Circulation, 210, 226 Coronary heart disease, 219, 226 Coronary Thrombosis, 226, 257, 260 Corpus, 145, 165, 226, 268, 292 Corpuscle, 226, 236 Cortex, 167, 226, 235, 236, 272, 277 Cortical, 9, 31, 35, 121, 129, 226, 237, 272, 280 Cortisol, 108, 207, 226 Cranial, 176, 221, 223, 226, 236, 244, 264, 265, 268, 289 Creatine, 17, 108, 114, 226 Creatine Kinase, 108, 226 Creatinine, 226, 252 Cribriform, 226, 264 Crossing-over, 226, 277 Crystallization, 57, 144, 226 Cultured cells, 32, 226 Curative, 161, 227, 262, 286 Cutaneous, 225, 227, 254, 290 Cyanide, 125, 227 Cyclic, 119, 218, 227, 242, 243, 263, 269, 286 Cycloserine, 53, 73, 126, 227 Cyclosporine, 53, 227 Cyst, 15, 69, 227 Cystathionine beta-Synthase, 227, 246 Cysteic Acid, 163, 227
Cysteine, 5, 15, 23, 36, 58, 59, 63, 75, 94, 95, 159, 170, 205, 227, 228, 285 Cysteinyl, 15, 21, 75, 147, 227 Cystine, 15, 27, 146, 147, 227 Cystoscopy, 85, 183, 227 Cytochrome, 20, 76, 227 Cytoplasm, 34, 56, 212, 215, 220, 227, 234, 235, 236, 259, 263, 279, 285 Cytoskeleton, 31, 52, 227, 249, 258 Cytotoxic, 10, 227 Cytotoxicity, 208, 227 D De novo, 15, 17, 19, 21, 109, 228 DEAE-Cellulose, 136, 228 Deamination, 228, 290 Decarboxylation, 216, 228, 245, 259, 275 Decidua, 228, 270 Decompensation, 208, 228 Decontamination, 45, 228 Defensins, 31, 208, 215, 228 Degenerative, 9, 43, 228, 244, 278 Dehydroepiandrosterone, 80, 228 Deletion, 7, 41, 43, 55, 56, 66, 74, 88, 212, 228, 240 Delirium, 212, 228 Delusions, 228, 267, 275 Dementia, 167, 212, 228 Denaturation, 153, 228, 271 Dendrites, 38, 228, 229, 261, 262, 264 Dendritic, 228, 256, 278, 283 Density, 56, 76, 220, 228, 253, 264, 271, 282 Dental Caries, 229, 239 Dentate Gyrus, 229, 245 Deoxyribonucleic, 229, 279 Deoxyuridine, 82, 229 Depersonalization, 229, 266, 279 Depolarization, 7, 27, 229 Depressive Disorder, 229, 254 Deprivation, 7, 41, 229 Derealization, 229, 266 Dermatitis, 68, 229 Dermis, 229, 278, 285, 288 DES, 31, 210, 229 Desensitization, 48, 76, 89, 98, 229 Detergents, 153, 229 Detoxification, 85, 229 Deuterium, 230, 246 Dextroamphetamine, 209, 230 Diabetes Mellitus, 4, 230, 241, 244 Diabetic Retinopathy, 14, 230 Diacetyl, 150, 230 Diagnostic procedure, 137, 182, 230
300
Glycine
Diaphragm, 13, 230 Diarrhoea, 230, 246 Diastolic, 230, 247 Diathermy, 108, 230 Diencephalon, 230, 235, 247, 272, 286 Diffusion, 157, 216, 230, 243, 250 Digestion, 208, 215, 217, 230, 250, 254, 268, 284 Digestive tract, 230, 281, 283 Dihydrotestosterone, 230, 277 Dilator, 39, 230 Dilazep, 85, 230 Dimethyl, 57, 230 Diploid, 124, 225, 230, 270 Dipyridamole, 85, 230 Discrete, 38, 230, 273, 286 Discrimination, 51, 60, 61, 94, 230 Disinfectant, 68, 231, 236 Disposition, 99, 231 Dissociation, 20, 207, 231, 250 Dissociative Disorders, 231 Distal, 26, 75, 214, 231, 233, 251 Diuretic, 231, 255, 282 Dizziness, 231, 266 DNA Topoisomerase, 231, 241 Dopa, 231, 253 Dopamine, 19, 27, 28, 30, 32, 35, 37, 165, 209, 212, 223, 230, 231, 253, 258, 262, 269, 279 Dormancy, 45, 231 Dorsal, 223, 231, 235, 271, 280 Dorsum, 231, 240 Dosage Forms, 171, 231 Double-blind, 53, 54, 78, 120, 232 Drive, ii, vi, 9, 34, 111, 232, 250 Drug Carriers, 172, 232 Drug Interactions, 232 Drug Resistance, 232 Drug Tolerance, 50, 232, 287 Duct, 209, 232, 237, 285 Duodenum, 215, 232, 234, 284 Dyes, 50, 209, 215, 232, 263, 285 Dyskinesia, 212, 232 Dyslexia, 13, 232, 252 Dysplasia, 170, 232 Dyspnea, 228, 232, 266 Dystrophic, 74, 78, 85, 232, 235 E Edema, 225, 228, 230, 232, 260 Effector, 205, 224, 232, 269 Efferent, 232, 259, 280
Efficacy, 7, 16, 35, 36, 40, 51, 53, 55, 89, 112, 118, 121, 142, 164, 165, 172, 232 Ejaculation, 232, 280 Elastic, 232, 282, 285 Elasticity, 173, 213, 233 Elastin, 89, 223, 233, 237 Electrode, 9, 45, 144, 149, 233 Electrolyte, 144, 228, 233, 252, 272, 281, 282 Electrons, 212, 233, 250, 266, 276 Electrophoresis, 46, 149, 205, 233 Electrophysiological, 11, 31, 38, 80, 112, 233 Electroshock, 233, 239 Elementary Particles, 233, 274 Embolism, 108, 233 Embryo, 120, 205, 216, 220, 233, 238, 248, 265, 272 Emulsion, 214, 233, 238 Enamel, 229, 233, 251 Encephalitis, 34, 233 Encephalitis, Viral, 233 Encephalocele, 233, 261 Encephalopathy, 72, 84, 96, 98, 100, 234 Endemic, 234, 255, 283 Endogenous, 10, 14, 28, 32, 60, 78, 80, 101, 217, 231, 234, 288 Endometrial, 101, 105, 108, 120, 234 Endometrium, 71, 228, 234 Endorphins, 234, 262 Endoscope, 234 Endoscopic, 67, 68, 213, 227, 234 Endothelial cell, 90, 217, 234, 238, 287 Endothelium, 234, 263 Endothelium-derived, 234, 263 Endotoxic, 234, 253 Endotoxins, 224, 234, 251 End-stage renal, 108, 222, 234 Energetic, 17, 234 Energy balance, 234, 252 Enflurane, 45, 234 Enhancers, 95, 234 Enkephalin, 39, 234 Enterocytes, 218, 234 Entorhinal Cortex, 235, 245 Environmental Exposure, 235, 264 Environmental Health, 101, 188, 190, 235 Enzymatic, 20, 21, 45, 50, 76, 209, 216, 218, 219, 224, 229, 235, 245, 271, 278 Enzyme Inhibitors, 235, 270 Enzyme Stability, 68, 235 Eosinophil, 235, 243
301
Epidermal, 62, 235, 256, 293 Epidermal Growth Factor, 62, 235 Epidermis, 229, 235, 251, 275 Epidermoid carcinoma, 235, 283 Epidermolysis Bullosa, 74, 78, 85, 235 Epigastric, 235, 266 Epinephrine, 206, 231, 235, 262, 263, 289 Epithalamus, 230, 235, 253 Epithelial, 48, 106, 157, 171, 206, 215, 216, 228, 235, 236, 267 Epithelial Cells, 106, 215, 235, 236 Epithelium, 156, 215, 234, 236, 264, 267 Epitope, 25, 141, 236 Epitope Mapping, 25, 236 Erectile, 145, 165, 236, 268 Erection, 145, 165, 236, 248 Erythema, 225, 236 Erythrocyte Membrane, 140, 236 Erythrocytes, 22, 140, 209, 210, 217, 232, 236, 244, 277, 280 Erythropoiesis, 101, 236 Escalation, 78, 236 Esophagus, 230, 236, 269, 277, 284 Estradiol, 172, 236 Ethanol, 5, 17, 72, 77, 80, 96, 108, 113, 121, 127, 135, 159, 207, 236, 237 Ether, 154, 236 Ethmoid, 236, 264 Eukaryote, 24, 236 Eukaryotic Cells, 24, 236, 248, 264, 265 Evoke, 168, 236, 284 Evoked Potentials, 108, 236 Excipients, 138, 168, 236 Excitability, 18, 237 Excitation, 9, 19, 46, 49, 220, 221, 237, 262 Excitatory, 9, 12, 13, 21, 30, 32, 46, 52, 54, 122, 158, 176, 237, 241, 242, 247, 252 Excitotoxicity, 7, 32, 237 Excrete, 237, 251 Exhaustion, 211, 237, 255 Exocrine, 19, 237, 266 Exogenous, 11, 60, 216, 234, 237 Exon, 64, 104, 208, 237 Extracellular Matrix, 26, 27, 225, 237, 249, 256, 265 Extracellular Matrix Proteins, 237, 256 Extracellular Space, 27, 32, 237 Extraction, 144, 237 Extrapyramidal, 207, 212, 231, 237 Extravasation, 237, 244 F Family Planning, 189, 237
Fat, 206, 215, 217, 218, 219, 220, 226, 237, 252, 253, 271, 282, 285, 289 Fatigue, 237, 244 Fermentation, 207, 237 Fertilizers, 238, 263, 285 Fetal Alcohol Syndrome, 18, 238 Fetal Development, 238, 261 Fetus, 60, 87, 112, 205, 238, 270, 272, 290 Fibrillation, 173, 238 Fibrinogen, 142, 143, 238, 270, 287 Fibroblast Growth Factor, 123, 170, 238 Fibronectin, 68, 142, 143, 238 Fibrosis, 208, 238, 279 Filtration, 153, 238, 252 Fissure, 224, 229, 238, 272 Fixation, 135, 238, 280 Flatus, 238, 240 Flumazenil, 7, 238 Fluorescence, 5, 51, 83, 239 Fluorine, 177, 239 Fluorouracil, 230, 239 Flurothyl, 7, 239 Folate, 16, 19, 20, 22, 24, 25, 29, 120, 229, 239 Fold, 48, 63, 238, 239 Folic Acid, 120, 239 Fossa, 183, 221, 239 Fovea, 238, 239 Fractionation, 239, 285 Frameshift, 130, 239, 289 Frameshift Mutation, 130, 239, 289 Free Radicals, 212, 231, 239, 260 Freeze-dried, 152, 159, 239 Frontal Lobe, 8, 239, 272 Frostbite, 239, 269 Fungi, 57, 120, 147, 211, 216, 225, 239, 243, 258, 283, 290, 293 Fungicides, Industrial, 211, 239 G Gait, 165, 221, 240 Galactosidases, 140, 240 Gamma-Glutamyltransferase, 23, 240 Ganglia, 205, 215, 240, 261, 268 Ganglion, 11, 14, 32, 44, 49, 223, 240, 278 Gap Junctions, 240, 285 Gas, 40, 124, 209, 219, 230, 238, 239, 240, 246, 256, 260, 263, 284, 291 Gas exchange, 240, 291 Gastric, 51, 96, 219, 231, 235, 240, 245, 246 Gastrin, 48, 67, 69, 81, 84, 86, 87, 99, 123, 240, 245
302
Glycine
Gastrointestinal, 51, 129, 176, 217, 235, 236, 240, 255, 281, 284 Gastrointestinal tract, 51, 236, 240, 281 Gelatin, 240, 287 Gels, 43, 149, 157, 240 Gene Deletion, 17, 41, 240 Gene Expression, 18, 26, 29, 130, 240 Gene Rearrangement, 18, 240 Gene Silencing, 160, 240 Generator, 183, 241 Genetic Code, 241, 263 Genetic Engineering, 160, 216, 223, 241 Genetic testing, 241, 271 Genistein, 119, 123, 124, 127, 241 Genotype, 22, 74, 241, 269 Germ Cells, 241, 256, 264, 266, 283, 286 Germinal Center, 35, 241 Gestation, 11, 241, 270 Gland, 206, 241, 254, 266, 270, 273, 280, 284, 285, 287 Glioma, 27, 30, 241 Glomerular, 241, 252, 256 Glomerular Filtration Rate, 241, 252, 256 Glomeruli, 241, 264 Glomerulus, 241, 261 Glucose, 3, 7, 30, 41, 76, 92, 106, 163, 217, 220, 230, 241, 242, 244, 249, 282 Glucose Intolerance, 230, 241 Glutamic Acid, 23, 65, 83, 132, 146, 147, 153, 172, 173, 239, 242, 262, 273 Glutamine, 5, 32, 63, 66, 78, 79, 105, 153, 172, 173, 242 Glutathione Peroxidase, 242, 280 Glutathione Transferase, 75, 242 Glycerol, 218, 242, 269 Glycolysis, 5, 242 Glycoprotein, 60, 70, 82, 122, 124, 166, 167, 238, 242, 243, 259, 269, 287 Glycosidic, 154, 211, 242, 261 Glycylglycine, 92, 242 Governing Board, 242, 272 Gp120, 242, 268 GP41, 65, 242 Grade, 171, 242 Graft, 242, 248, 260 Gramicidin, 12, 18, 242 Gram-positive, 31, 48, 242 Granule, 229, 242, 279 Granulocyte, 120, 242, 243 Granulocyte-Macrophage ColonyStimulating Factor, 120, 243 Graphite, 144, 243
Grasses, 239, 243 Growth factors, 17, 51, 170, 243, 261 Growth Plate, 77, 243 Guanine, 243, 275 Guanylate Cyclase, 243, 263 Gyrus Cinguli, 243, 253 H Haematoma, 69, 243 Haemodialysis, 175, 243 Haemorrhage, 161, 205, 243 Haemostasis, 87, 143, 243 Hair follicles, 229, 243, 292 Hallucinogen, 243, 269 Haploid, 243, 270 Haplotypes, 124, 243 Haptens, 207, 243 Headache, 218, 244, 248 Hearing Disorders, 224, 244 Heart attack, 219, 244 Heart failure, 17, 175, 244 Hematoma, 79, 244 Heme, 216, 227, 244, 266 Hemochromatosis, 27, 244 Hemodialysis, 244, 251, 252 Hemoglobin, 106, 210, 236, 244, 251, 252 Hemolysis, 236, 244 Hemolytic, 141, 244 Hemophilia, 87, 138, 168, 244 Hemorrhage, 244, 260, 275, 279, 284, 292 Hemostasis, 244, 249, 281 Hepatic, 29, 73, 87, 88, 94, 207, 228, 244, 254 Hepatitis, 44, 60, 161, 244 Hepatocellular, 44, 161, 244, 245 Hepatocellular carcinoma, 44, 161, 245 Hepatocyte, 221, 245 Hepatotoxicity, 130, 245 Herbicide, 155, 245 Hereditary, 27, 67, 153, 244, 245, 262, 278 Heredity, 240, 241, 245 Herpes, 117, 245 Herpes Zoster, 245 Heterodimers, 245, 249 Heterogeneity, 92, 207, 245 Heterogenic, 245 Heterogenous, 60, 245 Heterotrophic, 239, 245 Heterozygote, 89, 245 Hippocampus, 28, 30, 167, 229, 245, 253, 280, 284 Histamine, 210, 212, 245 Histidine, 29, 56, 152, 153, 245
303
Histones, 222, 245 Homeostasis, 12, 15, 48, 51, 245 Homologous, 42, 47, 147, 208, 226, 245, 259, 280, 285 Hormone, 24, 33, 48, 52, 206, 208, 226, 229, 235, 236, 240, 245, 249, 252, 257, 286, 287 Hormone therapy, 206, 245 Horseradish Peroxidase, 33, 150, 246 Human papillomavirus, 170, 246 Humeral, 35, 246 Hybrid, 33, 214, 223, 246 Hydration, 60, 205, 246 Hydrochloric Acid, 143, 246 Hydrogen Bonding, 56, 95, 163, 246 Hydrolases, 240, 246 Hydrolysis, 89, 103, 143, 213, 216, 246, 250, 259, 261, 271, 274 Hydrophobic, 56, 57, 89, 229, 246, 253 Hydroxylysine, 223, 246 Hydroxyproline, 209, 223, 246 Hyperhomocysteinemia, 108, 227, 246 Hyperkeratosis, 170, 246 Hypersensitivity, 64, 208, 229, 235, 246, 280 Hypertension, 26, 90, 169, 213, 219, 244, 246, 269 Hyperthermia, 230, 247 Hypnotic, 215, 247 Hypoglycemia, 32, 247 Hypokinesia, 176, 247, 267 Hypotension, 152, 212, 226, 247 Hypothalamus, 46, 230, 234, 247, 253, 270, 280 Hypothermia, 28, 247 Hypoxia, 5, 32, 119, 148, 228, 247 Hypoxic, 59, 148, 247 I Ibotenic Acid, 247, 259 Imaging procedures, 247, 288 Imidazole, 151, 245, 247 Immune response, 35, 141, 142, 206, 211, 243, 247, 255, 280, 284, 290, 292 Immune system, 141, 142, 146, 152, 216, 247, 248, 255, 293 Immunization, 194, 247, 248, 280 Immunoassay, 171, 247 Immunochemistry, 236, 247 Immunodeficiency, 65, 88, 96, 154, 166, 247 Immunogenic, 141, 247, 253 Immunoglobulin, 3, 59, 99, 156, 157, 211, 247, 259
Immunohistochemistry, 5, 9, 39, 247 Immunologic, 4, 221, 247 Immunology, 34, 75, 206, 207, 246, 248 Immunotherapy, 216, 229, 248 Impairment, 9, 13, 22, 32, 42, 221, 228, 232, 248, 257, 275 Impotence, 145, 165, 236, 248, 267, 269 Impotent, 145, 165, 248 In situ, 6, 140, 173, 248 In Situ Hybridization, 6, 248 In vitro, 6, 7, 11, 13, 14, 16, 21, 23, 31, 35, 40, 45, 55, 88, 90, 98, 100, 104, 170, 173, 218, 248, 271, 287 Incision, 248, 250 Induction, 20, 21, 40, 212, 230, 233, 248, 251 Infant Food, 71, 248 Infant, Newborn, 207, 248 Infarction, 217, 248, 277 Influenza, 34, 248 Infusion, 72, 97, 108, 248, 260, 288 Ingestion, 246, 248, 257, 271 Inhalation, 206, 234, 249, 251, 271 Initiation, 10, 23, 43, 58, 68, 249, 288 Inorganic, 249, 254, 259, 284, 285 Inositol, 98, 106, 249 Inotropic, 231, 249 Insecticides, 249, 269, 293 Insulin, 50, 106, 109, 170, 249 Insulin-dependent diabetes mellitus, 249 Insulin-like, 106, 170, 249 Integrase, 88, 249 Integrase Inhibitors, 88, 249 Integrins, 26, 249 Interferon, 156, 249 Interferon-alpha, 156, 249 Interleukin-2, 152, 249 Interneurons, 39, 249 Interstitial, 32, 66, 237, 250, 256, 261 Intestinal, 27, 48, 208, 218, 219, 234, 250, 255 Intestine, 31, 215, 217, 224, 250, 252 Intoxication, 228, 250, 293 Intracellular Membranes, 250, 256, 257 Intraepithelial, 170, 250 Intrathecal, 128, 250 Intravenous, 3, 51, 72, 109, 248, 250 Intrinsic, 11, 13, 27, 32, 42, 207, 215, 250 Invasive, 30, 145, 165, 171, 250, 255 Invertebrates, 250, 254 Involuntary, 215, 222, 238, 250, 260, 282
304
Glycine
Ion Channels, 5, 14, 15, 27, 36, 175, 214, 250, 285 Ion Transport, 27, 57, 250 Ionization, 94, 101, 250 Ionophores, 57, 250, 290 Ions, 10, 27, 49, 51, 56, 67, 144, 150, 151, 164, 205, 218, 231, 233, 246, 250, 258, 272, 274 Ipsilateral, 13, 250, 257, 277 Irrigation, 101, 135, 183, 250 Ischemia, 7, 10, 14, 32, 214, 217, 251, 260, 277 Ischemic stroke, 78, 148, 251 Isoenzyme, 108, 226, 251 Isoflavones, 118, 251 Isoflurane, 7, 45, 251 Isoleucine, 43, 50, 251 Isopropyl, 68, 251 Isozymes, 17, 29, 141, 251 J Jealousy, 251, 267 K Kainate, 148, 158, 251 Kb, 188, 251 Keratin, 73, 251 Ketamine, 50, 251, 269 Keto, 42, 251 Kidney Cortex, 40, 107, 251 Kidney Failure, 4, 234, 251, 252, 256 Kidney Failure, Acute, 251 Kidney Failure, Chronic, 251, 252 Kidney Glomerulus, 251, 252 Kinetic, 82, 93, 120, 252 Kynurenic Acid, 32, 252 L Labile, 60, 224, 252 Lactation, 91, 252 Language Disorders, 224, 252 Large Intestine, 224, 230, 250, 252, 277, 281 Laryngeal, 38, 252 Larynx, 252 Laxative, 252, 282 Learning Disorders, 167, 252 Lectin, 252, 257 Lens, 83, 252, 292 Leptin, 90, 252 Lesion, 23, 252, 254, 286, 290 Lethal, 58, 83, 214, 227, 252, 279 Leucine, 15, 90, 106, 109, 125, 126, 252 Leucocyte, 208, 235, 253 Leukemia, 118, 253 Leukocytes, 215, 217, 221, 249, 253, 259
Levodopa, 164, 165, 231, 253 Life cycle, 44, 144, 239, 253 Ligament, 253, 273 Ligands, 26, 30, 56, 82, 155, 158, 249, 253 Ligase, 253, 275 Limbic, 8, 209, 243, 253, 272 Limbic System, 8, 209, 243, 253, 272 Linkage, 154, 174, 240, 253 Linoleic Acids, 142, 253 Lip, 62, 253 Lipid, 10, 213, 222, 242, 249, 250, 251, 253, 266, 289 Lipid A, 10, 253 Lipid Peroxidation, 253, 266 Lipopolysaccharide, 64, 253 Lipoprotein, 253, 254, 292 Lipoxygenase, 126, 142, 213, 253 Lithium, 72, 144, 212, 254 Lithium Carbonate, 144, 254 Liver cancer, 44, 254 Liver Cirrhosis, 44, 254 Liver Transplantation, 81, 93, 102, 254 Localization, 13, 14, 24, 28, 52, 59, 73, 95, 130, 247, 254 Localized, 13, 64, 167, 217, 229, 238, 243, 244, 248, 254, 270, 286, 290 Locomotion, 254, 270 Loop, 47, 48, 62, 65, 69, 76, 88, 148, 254 Low-density lipoprotein, 142, 253, 254 Loxapine, 209, 254 Lumbar, 54, 254 Luminescence, 163, 254 Lupus, 4, 254 Lymph, 221, 226, 234, 254, 255, 284 Lymph node, 221, 254, 255 Lymphatic, 234, 248, 254, 255, 257, 282 Lymphatic system, 254, 255, 282 Lymphocyte, 35, 211, 255, 256 Lymphoid, 35, 118, 211, 241, 253, 255 Lysine, 83, 153, 159, 245, 246, 255, 273 M Macrophage, 243, 255 Magnetic Resonance Imaging, 8, 30, 255 Major Histocompatibility Complex, 66, 243, 255 Malabsorption, 92, 255 Malaria, 95, 255 Malaria, Falciparum, 255 Malaria, Vivax, 255 Malignancy, 255, 267 Malignant, 27, 170, 206, 212, 213, 254, 255, 261
305
Malnutrition, 92, 107, 207, 214, 255 Manic, 212, 254, 255, 275 Manifest, 214, 255 Mannitol, 78, 138, 152, 168, 255 Mass Fragmentography, 101, 256 Mastication, 256, 289 Matrilysin, 89, 256 Matrix metalloproteinase, 86, 89, 256 Maximum Tolerated Dose, 232, 256 Mechanical ventilation, 11, 256 Medial, 12, 39, 213, 223, 236, 243, 256, 265, 280 Mediate, 9, 31, 35, 39, 47, 89, 158, 223, 231, 256 Mediator, 27, 55, 231, 249, 256, 281 MEDLINE, 189, 256 Medullary, 39, 256 Megaloblastic, 101, 229, 239, 256 Meiosis, 256, 259, 285 Melanin, 256, 269, 289 Melanocytes, 256 Melanoma, 152, 256 Membrane, 8, 11, 13, 18, 25, 30, 32, 34, 37, 40, 47, 49, 52, 57, 63, 64, 67, 74, 83, 141, 167, 214, 220, 222, 224, 225, 229, 236, 237, 242, 243, 250, 252, 256, 257, 259, 260, 263, 265, 269, 271, 272, 278, 283, 285, 288, 292 Membrane Fusion, 34, 256 Membrane Proteins, 40, 257 Memory, 10, 28, 30, 69, 79, 228, 241, 257 Meninges, 220, 242, 257, 290 Menopause, 172, 257, 271 Menstruation, 228, 257 Mental, iv, 4, 30, 120, 188, 190, 221, 223, 224, 228, 231, 237, 238, 247, 257, 274, 275, 277, 279, 290 Mental deficiency, 238, 257 Mental Disorders, 247, 257, 274, 275 Mental Health, iv, 4, 30, 188, 190, 257, 275 Mental Processes, 231, 257, 275 Mental Retardation, 224, 257 Mesencephalic, 35, 257, 277 Mesenchymal, 235, 243, 257 Mesolimbic, 212, 257, 291 Metabolite, 216, 230, 257, 273 Metastasis, 256, 257 Metastatic, 152, 257 Methanol, 143, 257 Methicillin Resistance, 60, 257 Methionine, 15, 20, 22, 65, 106, 133, 159, 170, 230, 257, 285
Methyltransferase, 19, 41, 59, 73, 79, 85, 88, 127, 161, 257 MI, 69, 74, 89, 90, 92, 154, 203, 257 Micelle, 65, 257 Microbe, 142, 147, 257, 258, 288 Microbiology, 34, 123, 129, 206, 214, 258 Microcirculation, 254, 258 Microorganism, 223, 258, 267, 292 Microspheres, 232, 258 Microtubules, 258, 266 Migration, 51, 258 Mitochondria, 16, 20, 24, 25, 29, 32, 102, 258, 260, 265 Mitochondrial Swelling, 258, 261 Mitosis, 78, 212, 258 Mobility, 47, 258 Modeling, 10, 16, 56, 258 Modification, 33, 36, 40, 45, 100, 142, 209, 241, 258, 275 Modulator, 11, 32, 148, 258 Molecular mass, 157, 258 Molecular Structure, 258, 289 Monitor, 30, 33, 226, 258, 263 Monoamine, 209, 230, 258 Monoclonal, 62, 67, 73, 161, 259, 276 Monoclonal antibodies, 62, 73, 161, 259 Monocytes, 152, 253, 259 Mononuclear, 259 Mood Disorders, 167, 259 Morphological, 62, 233, 256, 259 Morphology, 8, 56, 118, 259 Motility, 259, 281 Motion Sickness, 259, 261 Motor Activity, 39, 46, 226, 259 Motor nerve, 170, 259, 264 Mucinous, 240, 259 Mucolytic, 205, 259 Mucosa, 48, 51, 234, 254, 259, 284 Mucus, 218, 259, 262 Multidrug resistance, 103, 167, 259, 269 Multivalent, 150, 259 Muramidase, 46, 259 Muscimol, 7, 259 Muscle Contraction, 13, 17, 259 Muscle Fibers, 259, 260 Muscle Spasticity, 167, 260 Musculature, 247, 260 Mutagen, 215, 260 Mutagenesis, 25, 34, 36, 41, 96, 260 Mutate, 56, 260 Myalgia, 248, 260 Myocardial infarction, 82, 226, 257, 260
306
Glycine
Myocardial Ischemia, 210, 260 Myocardial Reperfusion, 260, 277 Myocardial Reperfusion Injury, 260, 277 Myocardium, 17, 210, 257, 260 Myopathy, 93, 260 Myosin, 63, 259, 260 Myristate, 41, 260 N Nadir, 39, 260 Narcolepsy, 46, 230, 260 Nasal Mucosa, 248, 260 Nausea, 152, 211, 212, 231, 260, 266, 286, 290 NCI, 1, 187, 222, 261 Necrosis, 5, 63, 145, 165, 212, 217, 248, 257, 260, 261, 277, 280 Neocortex, 112, 261 Neonatal, 18, 64, 112, 157, 261 Neoplasm, 261, 267, 289 Nephritis, 99, 261 Nephrosis, 99, 261 Nerve Endings, 261, 285 Nerve Growth Factor, 170, 261 Nerve Regeneration, 170, 261 Nervous System, 9, 18, 29, 37, 45, 47, 52, 130, 146, 149, 158, 165, 175, 205, 207, 209, 215, 218, 220, 223, 230, 232, 236, 240, 242, 244, 253, 254, 256, 261, 262, 265, 268, 271, 281, 285, 286 Networks, 11, 261 Neural, 11, 12, 19, 22, 24, 30, 49, 122, 170, 207, 209, 234, 261, 262, 280 Neural tube defects, 22, 24, 261 Neuraminidase, 261, 267 Neurites, 170, 261 Neuroblastoma, 68, 262 Neurodegenerative Diseases, 102, 167, 215, 262 Neuroleptic, 207, 212, 262 Neurologic, 4, 42, 234, 262 Neuromuscular, 205, 262 Neuromuscular Junction, 205, 262 Neuronal, 6, 10, 11, 12, 14, 17, 32, 33, 35, 38, 45, 46, 72, 97, 149, 168, 169, 170, 176, 218, 262 Neurons, 7, 8, 9, 12, 13, 17, 26, 30, 31, 32, 33, 35, 38, 39, 43, 49, 52, 54, 62, 64, 81, 82, 107, 112, 122, 123, 148, 165, 170, 220, 223, 228, 229, 237, 240, 249, 253, 261, 262, 264, 278, 285 Neuropeptide, 66, 169, 262 Neurophysiology, 31, 122, 229, 262
Neuroretinitis, 262, 278 Neurotoxic, 27, 75, 247, 259, 262 Neurotoxicity, 35, 262 Neutralization, 162, 262 Neutrophil, 71, 97, 148, 262 Niacin, 79, 262, 289 Nickel, 150, 262 Night Blindness, 43, 262, 278 Ninhydrin, 136, 262 Nitric acid, 144, 263 Nitric Oxide, 5, 148, 263 Nitrogen, 15, 78, 101, 135, 136, 167, 208, 237, 238, 242, 252, 258, 263, 289 Nitrosamines, 263 Nitrosation, 96, 263 Nonmalignant, 48, 263 Nonverbal Communication, 224, 263 Norepinephrine, 206, 209, 231, 262, 263 Nosocomial, 49, 263 Nuclear Envelope, 263 Nuclear Pore, 24, 263 Nuclear Proteins, 5, 263 Nuclei, 8, 209, 223, 225, 233, 235, 241, 245, 255, 258, 263, 265, 271, 274, 280 Nucleic acid, 136, 149, 156, 158, 159, 160, 166, 167, 215, 218, 241, 248, 263, 264, 273, 275, 279 Nucleocapsid, 166, 264 Nucleolus, 264, 279 Nucleoproteins, 263, 264 Nucleus Accumbens, 112, 264, 291 O Oculomotor, 257, 264 Odour, 139, 264 Ointments, 231, 264, 293 Olfactory Bulb, 106, 264, 292 Olfactory Nerve, 264 Oliguria, 251, 252, 256, 264 Oncogene, 43, 68, 78, 102, 264 Oncogenic, 249, 264, 274 Oocytes, 6, 31, 45, 60, 64, 70, 80, 100, 120, 264 Opacity, 228, 264 Ophthalmology, 31, 49, 71, 109, 238, 264 Opiate, 234, 264 Opium, 264, 266 Opsin, 43, 264, 278 Optic Chiasm, 247, 265 Optic Nerve, 262, 265, 278 Organ Culture, 265, 287 Organelles, 220, 227, 256, 259, 265 Orofacial, 33, 265
307
Orthostatic, 212, 265 Osmolarity, 256, 265 Osmotic, 99, 207, 258, 265, 281 Ossification, 265 Osteoblasts, 265 Osteocalcin, 55, 265 Osteoclasts, 172, 265 Osteogenesis, 55, 58, 59, 63, 69, 76, 77, 83, 99, 104, 265 Osteogenesis Imperfecta, 55, 58, 59, 69, 76, 77, 83, 104, 265 Osteoporosis, 127, 172, 265 Ovaries, 172, 265 Ovary, 99, 236, 266 Ovum, 228, 241, 253, 266, 293 Oxidation, 15, 29, 42, 125, 142, 154, 155, 205, 212, 213, 216, 227, 242, 253, 266, 290 Oxidative metabolism, 40, 42, 206, 266 Oxidative Stress, 5, 21, 26, 35, 266 Oxides, 144, 242, 266 Oxygenase, 33, 266 Oxygenation, 142, 266 P Paclitaxel, 172, 173, 266 Palate, 266, 284 Palliative, 266, 286 Pancreas, 19, 205, 244, 249, 266 Pancreatic, 19, 69, 219, 266 Panic, 51, 176, 266 Panic Disorder, 51, 266 Papaverine, 145, 165, 264, 266 Papillary, 246, 267 Papilloma, 170, 171, 267 Papillomavirus, 171, 267 Paradoxical, 46, 267 Paralysis, 257, 267 Paramyxovirus, 166, 267 Paranoia, 168, 267 Parasitic, 267, 270, 279 Paresthesias, 266, 267 Parkinsonism, 212, 253, 267 Paroxysmal, 210, 267 Particle, 257, 267, 282, 288 Patch, 12, 13, 14, 18, 33, 49, 267, 288 Pathogen, 11, 160, 267 Pathogenesis, 14, 23, 41, 49, 64, 161, 267 Pathologic, 205, 212, 226, 246, 267, 278, 291 Pathologic Processes, 212, 267 Pathophysiology, 13, 267 Peak flow, 183, 267 Pedigree, 82, 267 Pelvic, 267, 273
Pelvis, 205, 254, 266, 267, 290 Penicillin, 45, 60, 64, 211, 257, 268, 290 Penis, 145, 165, 171, 232, 268, 269 Peptide Mapping, 62, 268 Peptide T, 46, 50, 268 Perch, 112, 268 Perennial, 127, 268 Perfusion, 247, 268 Periodontal disease, 23, 268 Peripheral blood, 208, 249, 268 Peripheral Nervous System, 262, 268, 284 Peripheral Vascular Disease, 268, 269 Peripheral vision, 268, 292 Peritoneal, 213, 268 Peritoneal Cavity, 213, 268 Perspiration, 139, 268 Pesticides, 216, 249, 269 Petechiae, 243, 269 P-Glycoprotein, 166, 269 Phallic, 238, 269 Pharmaceutical Solutions, 231, 269 Pharmacokinetic, 269 Pharmacologic, 7, 210, 269, 288 Pharynx, 248, 269 Phencyclidine, 37, 50, 269 Phenotype, 25, 26, 28, 42, 55, 63, 74, 77, 79, 148, 224, 240, 269 Phentolamine, 145, 165, 269 Phenyl, 33, 129, 174, 176, 269 Phenylalanine, 106, 153, 269, 289 Phosphodiesterase, 123, 269 Phospholipids, 237, 249, 253, 269 Phosphorus, 218, 269 Phosphorylation, 18, 35, 70, 121, 127, 269, 274, 290 Photoreceptor, 26, 269, 278 Physiologic, 14, 207, 216, 222, 231, 238, 247, 257, 270, 277, 278, 289 Phytotoxin, 270, 279 Picrotoxin, 90, 270 Pigment, 160, 216, 256, 270 Pilot study, 8, 270 Pituitary Gland, 238, 270 Placenta, 106, 236, 270 Plant Viruses, 147, 270 Plasma cells, 211, 270 Plasma protein, 138, 168, 207, 270, 274, 281 Plasticity, 6, 8, 10, 12, 13, 28, 55, 270 Platelet Aggregation, 208, 210, 263, 270 Platelets, 82, 213, 263, 270, 287 Platinum, 254, 270 Pleated, 251, 270
308
Glycine
Pleomorphic, 264, 271 Pneumonia, 4, 225, 271 Point Mutation, 18, 24, 37, 76, 103, 271 Poisoning, 228, 250, 261, 270, 271 Polyarthritis, 34, 271 Polyethylene, 118, 271 Polymerase, 5, 39, 271 Polymerase Chain Reaction, 39, 271 Polymers, 5, 151, 232, 271, 274 Polymorphism, 22, 58, 83, 271 Polypeptide, 50, 56, 130, 147, 156, 172, 209, 223, 235, 238, 242, 271, 273, 290, 293 Polyposis, 224, 271 Polysaccharide, 60, 119, 211, 220, 271 Polyunsaturated fat, 142, 271 Pons, 217, 271, 278 Posterior, 174, 210, 221, 222, 231, 235, 266, 271 Postmenopausal, 265, 271 Postnatal, 13, 238, 271 Postsynaptic, 12, 52, 71, 100, 271, 285 Post-synaptic, 6 Post-synaptic, 19 Post-synaptic, 156 Post-synaptic, 175 Post-synaptic, 272 Post-synaptic, 285 Post-translational, 33, 40, 272 Postural, 39, 165, 272 Potassium, 6, 14, 128, 148, 162, 272 Potassium Channels, 14, 272 Potentiate, 7, 45, 145, 146, 272 Potentiation, 7, 16, 17, 31, 33, 37, 65, 80, 82, 100, 110, 113, 272 Practice Guidelines, 190, 272 Precancerous, 171, 272 Precipitation, 163, 272 Prefrontal Cortex, 38, 272 Premalignant, 272 Prenatal, 82, 233, 238, 272 Prenatal Diagnosis, 82, 272 Preoperative, 183, 272 Presynaptic, 6, 100, 156, 261, 262, 272, 285 Prevalence, 161, 171, 272 Primary Biliary Cirrhosis, 70, 272 Primary tumor, 48, 272 Prion, 75, 95, 272 Probe, 10, 31, 47, 150, 273 Procollagen, 58, 69, 273 Prodrug, 176, 273 Progeny, 225, 273 Progression, 23, 210, 256, 273
Progressive, 35, 48, 77, 165, 213, 220, 222, 228, 232, 236, 252, 261, 262, 273, 278, 289 Projection, 38, 250, 263, 264, 265, 272, 273, 277, 291 Proline, 61, 62, 65, 71, 97, 105, 223, 246, 273 Promoter, 29, 42, 141, 154, 155, 273 Prone, 147, 273 Prophase, 259, 264, 273, 285 Prophylaxis, 3, 138, 153, 168, 273, 290 Prospective study, 171, 273 Prostate, 72, 78, 80, 108, 109, 132, 172, 173, 183, 273, 289 Protease, 11, 268, 273 Protein C, 5, 34, 48, 52, 94, 143, 207, 209, 214, 223, 251, 253, 265, 273, 290, 292 Protein Conformation, 34, 209, 251, 273 Protein Folding, 56, 273 Protein Isoforms, 208, 274 Protein Kinases, 18, 274 Protein S, 15, 21, 41, 43, 148, 153, 166, 170, 216, 241, 265, 273, 274, 279 Protein Subunits, 21, 274 Protein Transport, 24, 274 Protein-Tyrosine Kinase, 241, 274 Proteolytic, 34, 35, 72, 89, 208, 224, 235, 238, 274, 279 Prothrombin, 274, 287 Protocol, 3, 11, 22, 40, 274 Protons, 10, 246, 274, 276 Proto-Oncogene Proteins, 266, 274 Proto-Oncogene Proteins c-mos, 266, 274 Protozoa, 216, 225, 258, 274, 283, 290 Protozoan, 255, 274 Psychiatric, 37, 224, 257, 274 Psychiatry, 28, 53, 72, 85, 86, 87, 100, 118, 120, 126, 238, 274, 291 Psychic, 222, 257, 274, 275, 280 Psychoactive, 275, 293 Psychology, 30, 231, 275 Psychomotor, 228, 234, 262, 275 Psychosis, 37, 212, 275 Psychotomimetic, 209, 230, 275 Public Health, 50, 190, 215, 275 Public Policy, 189, 275 Publishing, 58, 275 Pulmonary, 159, 217, 251, 275, 285, 291 Pulmonary Edema, 251, 275 Pulse, 55, 234, 258, 275 Purines, 20, 22, 215, 275, 280 Purpura, 243, 275 Pyrimidines, 215, 275, 280 Pyruvate Carboxylase, 5, 275
309
Pyruvate Dehydrogenase Complex, 42, 275 Q Quality of Life, 53, 145, 165, 275 Quaternary, 47, 273, 276 R Race, 174, 231, 258, 276 Racemic, 174, 231, 276 Radiation, 128, 205, 206, 210, 214, 233, 235, 239, 247, 276, 293 Radiation therapy, 205, 206, 239, 276 Radio Waves, 230, 276 Radioactive, 214, 228, 246, 250, 259, 263, 264, 276 Radioisotope, 276, 288 Radiopharmaceutical, 241, 276 Raffinose, 138, 168, 276 Randomized, 78, 112, 117, 121, 232, 276 Randomized clinical trial, 117, 276 Rationalize, 16, 276 Reactive Oxygen Species, 21, 276 Reagent, 246, 262, 276 Reality Testing, 275, 276 Receptors, Serotonin, 277, 281 Recombinant, 6, 10, 25, 42, 51, 68, 77, 81, 84, 89, 93, 98, 99, 103, 138, 140, 168, 277, 291 Recombination, 42, 225, 240, 277 Reconstitution, 44, 84, 152, 277 Rectal, 67, 68, 183, 277 Rectum, 68, 212, 224, 230, 238, 240, 252, 273, 277, 289 Red blood cells, 103, 236, 244, 266, 277 Red Nucleus, 277, 291 Reductase, 20, 22, 58, 61, 76, 277, 287 Refer, 1, 218, 224, 231, 234, 238, 239, 245, 250, 254, 262, 263, 275, 277, 288 Reflux, 143, 277 Refraction, 277, 282 Regeneration, 7, 22, 49, 170, 238, 277 Regimen, 227, 232, 277 Rehabilitative, 55, 277 Relaxant, 266, 277 Reperfusion, 81, 82, 93, 102, 148, 260, 277 Reperfusion Injury, 81, 93, 102, 277 Resected, 48, 277 Resection, 67, 68, 71, 101, 277 Resorption, 265, 278 Respiration, 212, 219, 221, 258, 278 Respirator, 256, 278 Reticular, 39, 46, 278 Reticular Formation, 39, 278
Retina, 11, 14, 20, 26, 32, 43, 49, 107, 112, 222, 230, 252, 262, 265, 278, 279, 292 Retinal, 11, 14, 20, 26, 31, 42, 43, 49, 225, 230, 265, 278 Retinal Ganglion Cells, 20, 265, 278 Retinitis, 109, 278 Retinitis Pigmentosa, 109, 278 Retinol, 278 Retinopathy, 14, 230, 278 Retrograde, 39, 278 Retrospective, 73, 79, 278 Reversion, 278, 289 Rhodopsin, 264, 278 Ribonucleic acid, 61, 64, 136, 279 Ribose, 5, 206, 279 Ribosome, 147, 211, 279, 288 Ricin, 148, 279 Rickettsiae, 279, 290 Riluzole, 91, 279 Risk factor, 4, 16, 24, 161, 246, 273, 279 Risk patient, 4, 279 Risperidone, 87, 279 Rod, 214, 222, 269, 279 Rotenone, 125, 279 S Salicylic, 93, 279 Saliva, 259, 279 Sarcosine, 59, 86, 279 Schizoid, 279, 293 Schizophrenia, 37, 53, 73, 85, 86, 87, 100, 120, 132, 167, 194, 254, 267, 279, 291, 293 Schizotypal Personality Disorder, 229, 279, 293 Sclerae, 265, 279 Scleroproteins, 251, 279 Sclerosis, 213, 279 Screening, 171, 222, 280 Sebaceous, 229, 280, 292 Secretion, 19, 27, 79, 235, 245, 249, 252, 259, 268, 280 Secretory, 31, 49, 208, 280, 285 Sedative, 28, 215, 238, 280 Sedimentation, 220, 280, 289 Segregation, 43, 277, 280 Seizures, 10, 69, 127, 146, 228, 267, 280 Selenium, 146, 280 Semen, 122, 132, 232, 273, 280 Semisynthetic, 218, 280 Senile, 265, 280 Sensitization, 124, 280 Septal, 253, 280 Septal Nuclei, 253, 280
310
Glycine
Sequence Homology, 268, 280 Sequencing, 271, 280 Sequester, 156, 280, 285 Serologic, 247, 281 Serotonin, 19, 28, 39, 47, 209, 212, 262, 277, 279, 281, 289 Serum, 4, 70, 100, 108, 129, 150, 183, 207, 210, 224, 226, 252, 254, 265, 277, 281 Serum Albumin, 150, 281 Shock, 66, 119, 233, 281, 289 Side effect, 44, 164, 165, 206, 207, 212, 216, 220, 251, 281, 288 Sindbis Virus, 208, 281 Skeletal, 172, 222, 226, 281, 282 Skeleton, 154, 205, 281 Skin graft, 105, 281 Skull, 233, 261, 281, 286 Sleep apnea, 281, 284 Small cell lung cancer, 102, 281 Small intestine, 31, 232, 245, 250, 281 Smallpox, 281, 290 Smooth muscle, 26, 208, 210, 218, 245, 266, 281, 282, 284 Social Environment, 275, 281 Sodium, 64, 65, 148, 152, 162, 171, 281, 282, 285 Sodium Bicarbonate, 162, 282 Sodium Dodecyl Sulfate, 65, 152, 282 Soft tissue, 217, 281, 282 Solid tumor, 40, 154, 210, 282 Solvent, 159, 174, 215, 236, 242, 257, 265, 269, 282 Somatic, 222, 253, 256, 258, 267, 268, 272, 282 Somatic cells, 256, 258, 282 Sonogram, 282, 289 Sorbitol, 3, 163, 255, 282 Sound Localization, 13, 282 Sound wave, 230, 282, 289 Soybean Oil, 271, 282 Spasm, 226, 257, 282 Spasmodic, 124, 282 Specialist, 195, 282 Specificity, 84, 136, 148, 150, 167, 207, 213, 218, 282 Spectroscopic, 91, 106, 282 Spectrum, 56, 85, 147, 276, 282 Speech Perception, 13, 282 Sperm, 222, 283, 289 Spermatozoa, 280, 283 Sphincter, 183, 252, 283 Spike, 14, 38, 60, 283
Spina bifida, 261, 283 Sporadic, 262, 283 Spores, 120, 283 Squamous, 171, 235, 283 Squamous cell carcinoma, 171, 235, 283 Squamous cells, 283 Stabilization, 12, 152, 283 Stabilizer, 4, 152, 283 Steady state, 5, 283 Steel, 222, 283 Stellate, 94, 283 Sterile, 148, 283 Steroid, 64, 215, 226, 283 Stimulant, 209, 218, 230, 245, 270, 283, 290 Stimulus, 12, 232, 233, 236, 237, 250, 267, 284, 287 Stomach, 205, 230, 236, 240, 245, 260, 268, 269, 277, 281, 284 Stomatitis, 65, 284 Stool, 224, 252, 284 Strand, 47, 271, 284 Stress, 26, 43, 219, 226, 233, 261, 266, 284 Striatum, 38, 165, 264, 284 Stroke, 7, 51, 78, 88, 148, 168, 188, 219, 251, 284 Structure-Activity Relationship, 123, 284 Strychnine, 7, 35, 37, 59, 60, 71, 112, 118, 146, 167, 175, 284 Subacute, 248, 284 Subclinical, 248, 280, 284 Subiculum, 245, 284 Submaxillary, 235, 284 Subspecies, 282, 284 Substance P, 227, 257, 277, 280, 284 Substrate, 23, 24, 25, 32, 40, 41, 49, 160, 219, 235, 246, 261, 284 Substrate Specificity, 25, 160, 284 Suction, 238, 284 Sulfates, 106, 282, 284 Sulfur, 15, 23, 73, 99, 237, 242, 257, 284, 285 Sulfur Compounds, 23, 285 Sulfuric acid, 284, 285 Supplementation, 40, 120, 125, 126, 129, 285 Suppression, 62, 124, 160, 229, 240, 285 Surfactant, 10, 282, 285 Sweat, 139, 229, 268, 285 Sweat Glands, 229, 285 Sympathomimetic, 209, 230, 231, 235, 263, 285 Symphysis, 221, 273, 285
311
Symptomatology, 112, 121, 285 Synapse, 12, 43, 52, 156, 206, 262, 272, 285, 289 Synaptic, 8, 9, 12, 13, 28, 32, 33, 38, 43, 46, 47, 52, 58, 64, 156, 262, 285 Synaptic Transmission, 9, 33, 47, 52, 156, 285 Synaptic Vesicles, 58, 285 Synaptosomes, 106, 285 Synergistic, 63, 100, 286 Systemic, 4, 105, 156, 157, 217, 228, 235, 248, 276, 282, 284, 286, 290 Systolic, 125, 247, 286 Systolic blood pressure, 125, 286 T Tardive, 212, 286 Taurine, 70, 73, 74, 87, 97, 106, 175, 215, 286 Telencephalon, 215, 221, 286 Tellurium, 154, 155, 286 Temporal, 8, 28, 48, 130, 176, 209, 214, 244, 245, 286 Temporal Lobe, 8, 209, 214, 286 Tendon, 224, 240, 286 Testis, 236, 286 Testosterone, 277, 286 Tetanic, 9, 286 Tetanus, 286 Thalamus, 230, 235, 253, 272, 286 Theophylline, 275, 286 Therapeutics, 70, 79, 119, 156, 157, 169, 286 Thermal, 231, 271, 287 Thioredoxin, 61, 287 Thoracic, 54, 230, 287 Thorax, 205, 254, 287 Threonine, 49, 64, 74, 94, 95, 268, 274, 280, 287 Threshold, 237, 246, 287 Thrombin, 169, 238, 270, 273, 274, 287 Thrombocytes, 270, 287 Thrombomodulin, 273, 287 Thromboses, 160, 287 Thrombosis, 87, 142, 249, 274, 284, 287 Thrombus, 226, 248, 251, 260, 270, 287 Thyroid, 287, 289 Thyroxine, 207, 269, 287 Tissue Culture, 52, 124, 261, 287 Tissue Extracts, 30, 287 Tolerance, 5, 28, 59, 206, 241, 287 Tone, 26, 287 Tonus, 287, 288
Tooth Preparation, 206, 288 Topical, 117, 139, 213, 236, 282, 288, 293 Toxic, iv, 57, 66, 148, 215, 225, 227, 232, 235, 242, 243, 257, 262, 263, 270, 280, 288, 290 Toxicity, 25, 35, 40, 72, 123, 152, 232, 256, 288 Toxicokinetics, 288 Toxicology, 20, 50, 88, 190, 288 Toxin, 61, 66, 69, 234, 286, 287, 288 Trace element, 239, 262, 288 Tracer, 15, 246, 288 Traction, 222, 288 Transcription Factors, 21, 160, 288 Transdermal, 95, 288 Transduction, 26, 36, 40, 48, 96, 249, 288 Transfection, 216, 288 Transferases, 21, 40, 288 Transfusion, 140, 288 Transgenes, 28, 141, 288 Translation, 56, 209, 211, 288 Translational, 241, 288 Translocation, 24, 25, 274, 289 Transmitter, 6, 19, 26, 175, 205, 214, 231, 250, 256, 263, 285, 289 Transplantation, 81, 102, 222, 247, 252, 255, 289 Transrectal ultrasound, 183, 289 Transurethral, 72, 78, 80, 108, 109, 183, 289 Transurethral resection, 72, 78, 80, 108, 109, 183, 289 Trauma, 148, 168, 215, 228, 244, 261, 289 Tremor, 165, 257, 267, 289 Tricyclic, 77, 289 Trigeminal, 33, 289 Trigger zone, 212, 289 Triglyceride, 139, 289 Trophic, 48, 62, 289 Tryptophan, 89, 153, 170, 223, 281, 289 Tubercle, 264, 289 Tuberculosis, 227, 254, 279, 289 Tubulin, 52, 109, 258, 289 Tumour, 240, 289 Tunica, 259, 289 Typhimurium, 59, 289 Tyrosine, 58, 68, 73, 80, 81, 84, 119, 121, 153, 164, 231, 274, 289 Tyrothricin, 242, 290 U Ulcer, 290 Ulceration, 94, 290 Unconscious, 210, 276, 290
312
Glycine
Uncoupling Agents, 250, 290 Urea, 70, 88, 163, 252, 285, 290 Urease, 262, 290 Uremia, 251, 290 Ureters, 290 Urethra, 268, 273, 289, 290 Urinary, 92, 94, 99, 101, 107, 109, 163, 227, 264, 290 Urinary tract, 92, 227, 290 Urinary tract infection, 227, 290 Urine, 63, 101, 106, 211, 216, 226, 231, 235, 252, 264, 290 Uterus, 205, 221, 226, 228, 234, 257, 266, 290 V Vaccination, 290 Vaccines, 45, 290, 292 Vaccinia, 122, 290 Vagina, 171, 221, 229, 257, 290 Vaginal, 171, 290 Valine, 18, 77, 82, 95, 107, 109, 122, 124, 166, 167, 173, 290 Variola, 290, 291 Vasoconstriction, 235, 243, 291 Vasodilation, 267, 291 Vasodilator, 208, 217, 230, 231, 245, 260, 267, 291 Vasomotor, 26, 291 Vector, 288, 291 Vein, 250, 263, 291 Venom, 70, 291 Venous, 108, 145, 161, 165, 217, 228, 274, 291 Venous blood, 145, 165, 217, 291 Venter, 291 Ventilation, 291 Ventral, 17, 123, 223, 247, 264, 271, 291 Ventral Tegmental Area, 17, 123, 291 Ventricle, 209, 220, 235, 245, 247, 264, 275, 286, 291 Venules, 217, 218, 258, 291 Vertebrae, 283, 291 Vesicular, 65, 245, 274, 281, 291
Veterinary Medicine, 149, 189, 291 Vial, 159, 291 Vinblastine, 289, 291 Vincristine, 289, 292 Viral Proteins, 41, 292 Virion, 214, 264, 292 Virulence, 23, 60, 92, 214, 288, 292 Visceral, 176, 253, 292 Viscosity, 205, 292 Visual field, 20, 265, 278, 292 Vitamin A, 249, 278, 292 Vitreous, 14, 222, 230, 252, 278, 292 Vitreous Body, 14, 222, 278, 292 Vitreous Hemorrhage, 230, 292 Vitro, 6, 11, 46, 55, 170, 292 Vivo, 6, 7, 11, 12, 15, 16, 18, 19, 21, 22, 23, 24, 30, 35, 37, 38, 40, 41, 46, 49, 52, 55, 56, 79, 88, 91, 92, 125, 138, 169, 170, 172, 173, 232, 248, 292 Voltage-gated, 12, 292 Vomeronasal Organ, 264, 292 Vomica, 284, 292 Vulgaris, 126, 135, 292 W Wakefulness, 46, 228, 292 Warts, 171, 246, 293 White blood cell, 211, 242, 253, 255, 259, 262, 270, 293 Withdrawal, 127, 228, 269, 293 Wound Healing, 52, 143, 238, 249, 256, 293 X Xenobiotics, 21, 293 Xenograft, 210, 293 X-ray, 18, 41, 57, 110, 174, 239, 260, 263, 276, 283, 293 Y Yeasts, 239, 269, 293 Z Zebrafish, 67, 293 Zinc Oxide, 117, 293 Zygote, 225, 293 Zymogen, 273, 293
