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
