BASAL GANGLIA 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., 1960Basal Ganglia: 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: 0-497-00127-6 1. Basal Ganglia-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 basal ganglia. 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 BASAL GANGLIA ....................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Basal Ganglia ................................................................................ 5 E-Journals: PubMed Central ....................................................................................................... 63 The National Library of Medicine: PubMed ................................................................................ 64 CHAPTER 2. NUTRITION AND BASAL GANGLIA ........................................................................... 109 Overview.................................................................................................................................... 109 Finding Nutrition Studies on Basal Ganglia............................................................................. 109 Federal Resources on Nutrition ................................................................................................. 111 Additional Web Resources ......................................................................................................... 112 CHAPTER 3. ALTERNATIVE MEDICINE AND BASAL GANGLIA..................................................... 113 Overview.................................................................................................................................... 113 National Center for Complementary and Alternative Medicine................................................ 113 Additional Web Resources ......................................................................................................... 117 General References ..................................................................................................................... 118 CHAPTER 4. DISSERTATIONS ON BASAL GANGLIA....................................................................... 119 Overview.................................................................................................................................... 119 Dissertations on Basal Ganglia.................................................................................................. 119 Keeping Current ........................................................................................................................ 120 CHAPTER 5. BOOKS ON BASAL GANGLIA ..................................................................................... 121 Overview.................................................................................................................................... 121 Book Summaries: Federal Agencies............................................................................................ 121 Book Summaries: Online Booksellers......................................................................................... 122 Chapters on Basal Ganglia......................................................................................................... 122 CHAPTER 6. PERIODICALS AND NEWS ON BASAL GANGLIA ....................................................... 125 Overview.................................................................................................................................... 125 News Services and Press Releases.............................................................................................. 125 Academic Periodicals covering Basal Ganglia ........................................................................... 126 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 131 Overview.................................................................................................................................... 131 NIH Guidelines.......................................................................................................................... 131 NIH Databases........................................................................................................................... 133 Other Commercial Databases..................................................................................................... 135 The Genome Project and Basal Ganglia ..................................................................................... 135 APPENDIX B. PATIENT RESOURCES ............................................................................................... 139 Overview.................................................................................................................................... 139 Patient Guideline Sources.......................................................................................................... 139 Finding Associations.................................................................................................................. 142 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 145 Overview.................................................................................................................................... 145 Preparation................................................................................................................................. 145 Finding a Local Medical Library................................................................................................ 145 Medical Libraries in the U.S. and Canada ................................................................................. 145 ONLINE GLOSSARIES................................................................................................................ 151 Online Dictionary Directories ................................................................................................... 151 BASAL GANGLIA DICTIONARY............................................................................................. 153
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INDEX .............................................................................................................................................. 219
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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 basal ganglia 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 basal ganglia, 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 basal ganglia, 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 basal ganglia. 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 basal ganglia, 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 basal ganglia. 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 BASAL GANGLIA Overview In this chapter, we will show you how to locate peer-reviewed references and studies on basal ganglia.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and basal ganglia, 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 “basal ganglia” (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: •
Voiding and MRI Analysis of the Brain Source: International Urogynecology Journal. 10(3): 192-199. 1999. Contact: Available from Springer-Verlag New York Inc. 175 Fifth Avenue, New York, NY 10010. (212) 460-1500. Fax (212) 473-6272. Summary: Observations of surgery, angiography, and postmortem studies have indicated that the frontal lobe of the brain is a higher center important in the control of micturition (urination). CT scan and magnetic resonance imaging (MRI) have made it possible to extend these early results. This article reports on a study of imaging in patients with hemispheric and brainstem strokes. In a series of stroke patients, urinary dysfunction was found in 68 percent of these patients with frontal lesions, 20 percent of patients with parietal lesions, 14 percent with temporal lesions, and none of the patients
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who had occipital lobe lesions. With lesions in the frontal lobe, it appears that medial aspects are particularly important in the prefrontal lobe, cigulate gyrus, paracentral lobule, and the orbital area in micturition control. Frontal lobe disease may cause disorders of storage as well as voiding, as shown by urodynamics: detrusor hyperreflexia, detrusor areflexia, uninhibited sphincter relaxation, and unrelaxing sphincter on voiding were found. The authors also make observations about the role of the basal ganglia and pons in micturition control in humans. 6 figures. 47 references. •
Frontal Functions in Normal Aging and the Performance in Purdue Pegboard Test Source: Research and Practice in Alzheimer's Disease. 151-162. 1998. Summary: This article discusses a study that analyzed the relationship between manual motor ability measured with the Purdue Pegboard (PP) and frontal lobe functions in 62 healthy subjects aged 65 to 87. Researchers used a neuropsychological battery to measure the performance in frontal lobe functions; the PP test classified subjects into two different groups. Results showed significant differences between subjects with and without motor difficulties. The group with lower PP scores presents more deficits in performing frontal-lobe associated activities. These results support the hypothesis that dopaminergic basal ganglia dysfunctions may play an important role in frontal lobe deficits associated with normal aging. Other recent findings showed a positive correlation between atrophy in substantia nigra and deficits in PP execution. 2 figures, 2 tables, 52 references (AA-M)
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Psychiatric and behavioral aspects of dementia of the Binswanger type Source: American Journal of Alzheimer's Disease. 173-178. July-August 1998. Summary: This article presents a literature review and case studies to discuss four symptom-clusters associated with Binswanger's disease. The four symptom clusters are late-onset paranoid psychosis, confused state, depression, and a behavioral syndrome of the frontal lobe type. The symptomatology cannot be regarded as mutually exclusive because features may overlap. The symptoms may precede the intellectual deterioration and motor disturbances that are seen with Binswanger's disease. Binswanger's disease, or subacute arteriosclerotic encephalopathy, is characterized by diffuse myelination of the brain's white matter and lacunar lesions in the basal ganglia and brain stem. Clinically it is a dementing illness associated with varied clinical and radiological abnormalities. The clinical features of Binswanger's disease are highly variable and the psychiatric and behavioral manifestations have not been well described. White matter lesions, cortical-cortical, and cortical-subcortical connectivities in the genesis of psychosis are interesting subjects for further study. 40 references.
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New Heights in Speech Research Source: ADVANCE for Speech-Language Pathologists and Audiologists. 8(26): 6-9. June 29, 1998. Summary: This article, from a professional newsletter for audiologists and speech language pathologists, hypothesizes that the same brain regions that govern thought may be involved in controlling speech. The author reports on a research study in which motor control and cognitive functions were measured in high-altitude, oxygen-poor situations (mountain climbing). Time needed to comprehend simple spoken English sentences increased by 50 percent at higher altitudes. The researchers theorized that the deterioration in cognition and motor control observed at higher altitudes might be due to selective dysfunction of the basal ganglia, the same brain structures implicated in
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studies of patients with Parkinsons disease. However, some tasks are unaffected at high altitudes. For example, no negative effect was found on some cognitive tests, such as the confrontation naming test, digit span tests, and the odd-man-out test. The investigators also established the viability of remote monitoring of neural functions, a precursor to determining how to implement this tool in a practical way. The article concludes with the contact information for the clinicians and researchers interviewed. 5 figures. •
Frontal Lobe Volume in Patients With Huntington's Disease Source: Neurology. 50: 252-258. January 1998. Summary: This journal article describes a study of frontal lobe volume in 20 patients with Huntington's disease (HD). The participants included 10 patients who were mildly affected and 10 who were moderately affected from the Baltimore Huntington's Disease Project, Johns Hopkins University School of Medicine, Maryland, and 20 healthy, matched controls. Magnetic resonance imaging was used to measure gray and white matter volumes within the frontal lobes. Symptom severity was assessed with the Quantified Neurological Examination, and cognitive function with a neuropsychological test battery. In mildly affected patients, frontal lobe gray and white matter volumes were almost identical to those of controls, despite clearly abnormal basal ganglia. Moderately affected patients exhibited significant reductions in total frontal lobe volume (17 percent) and frontal white matter volume (28 percent). Reductions in frontal white matter volume, but not total frontal lobe volume, were disproportionately greater than overall brain volume reductions. Frontal lobe volume correlated with symptom severity and general cognitive function, but these correlations did not remain significant after controlling for total brain volume. The authors conclude that cognitive impairment and symptom severity are associated with frontal lobe atrophy but that this association is not specific to the frontal lobes. 1 figure, 3 tables, 28 references.
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Role of Copper in Wilson's Disease Source: Contemporary Gastroenterology. p. 45-47, 50-51. July-August 1991. Summary: Wilson's disease is an autosomal recessive disorder, characterized by progressive deposition of copper in the liver and the basal ganglia of the brain. This article reviews the role of copper in Wilson's disease. The author notes that once adequate copper chelation has been achieved, lifelong maintenance therapy with penicillamine, a low-copper diet, and oral zinc may suffice. The alternative therapy is liver transplantation. Transplantation has been proposed for the treatment of patients with irreversible neurologic manifestations of Wilson's disease, since slow but complete resolution of neurologic symptoms occurs after liver transplantation. However, this therapy is controversial when hepatic function is not impaired. One sidebar reviews the pathogenesis of copper overload. 3 figures. 3 tables. 13 references.
Federally Funded Research on Basal Ganglia The U.S. Government supports a variety of research studies relating to basal ganglia. 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
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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
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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 basal ganglia. 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 basal ganglia. The following is typical of the type of information found when searching the CRISP database for basal ganglia: •
Project Title: A MOUSE MUTANT AS A MODEL OF SCHIZOPHRENIA Principal Investigator & Institution: Horowitz, Judith M.; Psychology; Medaille College 18 Agassiz Cir Buffalo, Ny 14214 Timing: Fiscal Year 2002; Project Start 16-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The transgenic ckr mice expressing an insertional mutation develop a progressive behavioral phenotype with motor symptoms resembling those seen in schizophrenia. As schizophrenia is a progressive brain disease of early development that affects forebrain neurons and circuits and ultimately behavior, there may be a relationship between disrupted forebrain development and basal ganglia dysfunction produced by the above insertional mutation. Here we will test this possibility by characterizing the behavioral deficits in ckr mice using a battery of behavioral tests selected to measure aspects of locomotion, hyperactivity, circling and sensorimotor gating. Further, we will test the ability of atypical antipsychotic agents and glutamate receptor agonists at preventing or attenuating the motor dysfunctions in ckr mice. As it is likely that the basic cellular and molecular mechanisms for initial regional and circuit differentiation in the forebrain is similar in most mammals, we propose to examine aberrations in forebrain development in the ckr mouse. This hypothesis is supported by preliminary studies that show enlargement of the lateral ventricles and a paucity of myelin fibers in the transgenic mouse striatum. To accomplish these research aims, the use of various combinations of immuno- and in situ hybridization and histochemical experiments, magnetic resonance neuroimaging techniques, and discrete pharmacological and behavioral manipulations will be used to elucidate further the cause and course related to the pathophysiology of schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: A2A SENSITIZATION
ADENOSINE
RECEPTORS
IN
PSYCHOSTIMULANT
Principal Investigator & Institution: Schwarzschild, Michael A.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 25-JUL-2001; Project End 31-MAY-2006 Summary: The adenosine A2A receptor offers a novel and compelling target for the modulation of addictive behaviors. Its expression in brain is largely restricted to the nucleus accumbens and straitum, where dopamine, glutamate and other neurotransmitters contribute to the sensitizing and reinforcing effects of psychostimulants. The striatal A2A receptor can modulate the release of these (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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neurotransmitters as well as their postsynaptic effects. In addition, it influences both the acute behavioral effects of psychostimulants, and (based on our preliminary studies) the behavioral sensitization induced by repeated psychostimulant exposure. These discrete anatomical, neuromodulatory and behavioral features point to an underappreciated role of A2A receptors in basal ganglia physiology and addiction biology. We propose (in response to NIDA PA-99-033) to investigate the role of the A2A receptor in behavioral sensitization and self-administration models of psychostimulant addiction. Our core hypothesis that A2A receptor inactivation attenuates the behavioral and biochemical changes induced by repeated psychostimulant administration will be systematically tested using complementary genetic and classic pharmacological approaches to A2A receptor inactivation. Specific Aim 1 will characterize the attenuation of amphetamineinduced locomotor sensitization and cocaine self-administration observed in A2A receptor knockout (A2A KO) mice. The effects of A2A receptor antagonists on the development and expression of psychostimulant-induced sensitization will then be correlated with the A2A KO phenotype. Specific Aim 2a will explore A2A receptorfacilitated neurotransmitter release as potential presynaptic mechanism of behavioral sensitization. In vivo microdialysis studies will focus on how A2A receptor inactivation affects the enhanced release of dopamine, glutamate and acetylcholine that contributes to behavioral sensitization. Specific Aim 2b seeks to identify postsynaptic mechanisms involved in A2A receptor regulation of behavioral sensitization. We will examine the effects of A2A receptor deficiency on a potential mediator (deltaFosB) and modulator (NAC-1) of the postsynaptic adaptations sustaining behavioral sensitization. Together these studies will clarify the role of A2A receptors in psychostimulant-induced addictive behaviors, and thus may encourage the development of novel, specific strategies for treating psychostimulant abuse and related addiction disorders Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADVANCED METHODS FOR MICROELECTRODE GUIDED NEUROSURGERY Principal Investigator & Institution: Mewes, Klaus; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 14-SEP-2000; Project End 31-MAY-2004 Summary: (Verbatim from the Applicant's Abstract) Development and clinical testing of an improved brain mapping and lesioning system is proposed. An improved MRI scan protocol, the intraoperative use of patient-specific MRI data and automation of major components of the microelectrode-guided neurosurgical procedure are key features of this system. These efforts are anticipated to improve the accuracy of lesion and/or deep brain stimulating electrode placement and to increase the efficiency and safety of this procedure. Increased usage and availability of this class of procedures is expected due to 'ease of use' characteristics achieved by automating many of the difficult and time consuming tasks. System development and enhancement will be based on the microelectrode-guided pallidotomy procedure pioneered at Emory University. A high resolution, high contrast MRI protocol will be developed for better visualization basal ganglia (BG) structures and greater spatial accuracy. It will be used to generate 3D mapping templates from patient-specific data volumes. Software for intra-operative useage will have the following functions: 1) automatic classification of neuronal discharge patterns and detection of BG nuclear boundaries, 2) automated detection of sensory-motor driving and visual evoked responses, 3) generation and co-registration of microelectrode trajectory plots with MRI incorporating data from 1 and 2, and 4) automated best-fit analysis to correlate recording track information with the MRI-based
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patient-specific MRI data volume. The system performance for neuronal pattern classification and BG nuclear boundary detection, sensory-motor driving and visual evoked response detection, microelectrode track generation, and track to template bestfit analysis will be compared individually to that of human experts. Upon achieving successful performance, a working prototype will be developed near the end of the second year that integrates these components and the clinical evaluation phase of the system will begin. Lesion accuracy, operating time, and a number of tracks required using the proposed system will be compared to similar data from procedures performed at Emory University using previous methods and technology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE MODERATES HIV-RELATED CNS DYSFUNCTION Principal Investigator & Institution: Becker, James T.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2006 Summary: (provided by applicant): During the course of the HIV/AIDS epidemic there has been one constant - ten percent of all new cases occur in adults over the age of 50. In spite of this, the vast majority of all HIV/AIDS research has focused or individuals younger than 50. With the increasing survival of AIDS patients, and the unrelenting rate of new infectiodcases, the number of AIDS patients over 50 years of age is growing. Our lack of understanding about how age and HIV/AIDS interact is becoming increasingly problematic, no more so than in the area of the neurocognitive manifestations of AIDS, since age is itself an important predictor of neurocognitive syndromes- In spite of the known links between age and various neuropsychiatric disorders - including dementia it has only been recently that much attention has been paid to the possible interactions between HIV/AIDS and aging and neuropsychiatric presentation. The purpose of this study is to compare and contrast neuropsychological deficits, including brain structural and functional abnormalities associated with HIV/AIDS as a function of chronological age. In particular, we will characterize the neuroimaging and neuropsychological defects in older individuals with AIDS focusing on two distinct neuropathologies that can lead to impairment - one via mesial temporal dysfunction (aging), and the other via basal ganglia dysfunction (AIDS). By carefully characterizing the neuropsychological deficits (including those identified using brain imaging technology) we will be better able to understand the interactive effects of agingand HIVIAIDS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: AGING AND DOPAMINE GRAFTS IN PARKINSONIAN MONKEYS Principal Investigator & Institution: Collier, Timothy J.; Professor; Rush University Medical Center Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) Transplantation of embryonic dopamine (DA) neurons as an experimental therapy for Parkinson's disease (PD) is currently under evaluation. The non-human primate treated with the neurotoxin MPTP has served as an important animal model for the disease and the grafting paradigm, and has had significant predictive value for results of early clinical trials. Despite some encouraging clinical findings, relative survival of grafted DA neurons is low and improvement of behavioral symptoms is incomplete. Part of the disparity between results in animals and PD patients may relate to failure of animal studies to model certain characteristics of potential recipients of graft therapy that impact significantly on
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the environment of grafted cells. One characteristic of this patient population that can be examined in animals is the influence of chronological age of the transplant recipient. The interactions between age-related changes inherent to this system in graft recipients, the response of the aging system to accelerated loss of nigral DA neurons, and the impact these changes have on the environment for grafted tissue only recently have received attention. We have found that the viability and function of grafted DA neurons is profoundly diminished in DA-depleted aged rats. In addition, these aged animals exhibit important deficits in compensatory responses to DA depletion including decreased striatal neurotrophic activity. Recent clinical results also suggest diminished graft efficacy in elderly patients. Advancing chronological age of the transplant recipient may represent a previously under-appreciated risk of diminished graft viability and function that may mandate study of novel grafting strategies 1 to achieve good therapeutic results. It is the goal of this proposal to evaluate the influence of chronological age of the host on graft viability and function in MM?-treated non-human primates. Tissue from single donors will be divided for implantation into pairs of young adult and aged hemiparkinsonian monkeys, with behavioral, mophological, and biochemical techniques employed to study rates of apoptosis in grafts, survivai, neurite outgrowth and release of DA from grafted cells, and receptor, metabolic and -trophic responses in the host. Additional analyses will examine aging-related changes in microvasculature and oxidative stress in the graft environment. These studies will provide valuable information on the response of the aged brain to accelerated DA neuron loss, the interaction between aging in the host and graft viability, indicate mechanisms of intervention with graft survival and function in the aged brain, and will aid in matching patients with the optimal therapeutic approach. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGING OF CENTRAL DOPAMINERGIC SYSTEMS IN PRIMATES Principal Investigator & Institution: Gash, Don M.; Professor and Chair; Anatomy and Neurobiology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2003; Project Start 18-FEB-1997; Project End 31-JAN-2008 Summary: (provided by applicant): Behavioral slowing is one of the cardinal features of human aging, contributing to the debilitating deterioration of motor functions in senescence. Our principal hypothesis for the past five years of research on this Program Project has been that changes in central dopaminergic pathways constitute a fundamental component of age-associated motoric declines. Converging evidence from our studies and others are providing strong support for this hypothesis. Our experimental plan for the next five years is designed to further our understanding of CNS processes underlying behavioral slowing and analyze therapeutic approaches for intervention. Specifically, our studies focus on the dopamine (DA) neurons in the substantia nigra (SN) and their projections to the caudate nucleus, putamen and globus pallidus of the basal ganglia. The proposed studies will analyze key junctions in the neural circuitry regulating motor functions in the basal ganglia, using behaviorally characterized female rhesus monkeys ranging in age from young adulthood to old age (5-25years+) as a model of human aging. Collectively, the three Projects and three supporting Cores in this Program will critically test the following hypotheses: Hypothesis 1 - That while changes in dopaminergic functions occur throughout the basal ganglia, alterations in neural processing in the SN is a principal component of age-associated motor declines. Hypothesis 2 - That functional changes in the basal ganglia dopaminergic system, including in tyrosine hydroxylase (TH), dopamine transporters (DAT) and DA receptors, are closely associated with age-associated motoric
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declines. Hypothesis 3 - That anatomical changes in normal aging in the basal ganglia are less predictive than functional changes of age-associated declines in motoric performance. Hypothesis 4 - That local administration of the potent dopaminergic trophic factor GDNF (glial cell line-derived neurotrophic factor) into the SN significantly repairs and restores age-associated declines in SN dopaminergic functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASTROCYTE CYTOKINE EXPRESSION/ION TRANSPORT IN ADC Principal Investigator & Institution: Benos, Dale J.; Professor & Chair; Physiology and Biophysics; University of Alabama at Birmingham Uab Station Birmingham, Al 35294 Timing: Fiscal Year 2002; Project Start 01-SEP-1993; Project End 31-JUL-2004 Summary: Central nervous system (CNS) involvement often occurs in individuals infected with human immunodeficiency virus type-1 (HIV-1). The most common clinical syndrome characterized by cognitive, motor, and behavioral disturbances is the acquired immunodeficiency syndrome (AIDS) dementia complex (ADC) or HIVassociated dementia (HAD), and is unique to HIV-1 infection. Although anti-retroviral agents (RT and protease inhibitors) are being used in HIV-infected individuals, it is not yet clear how these agents will affect HAD or if these drugs can even penetrate the brain. Thus, a major problem facing HAD patients is the that drugs used to combat systemic viral infection may not influence the CNS, a potential reservoir for virus. Because the physiological status of the brain in AIDS patients cannot be readily sampled, there is a critical need for the development of non-invasive techniques to detect and monitor the extent of HIV- associated cognitive/motor disorders. In this application, we intend to translate basic science findings obtained in the previous grant period to the human, and perform clinical cognitive studies on HIV-infected patients. We will develop non- invasive methodologies, based on 31P nuclear magnetic resonance (NMR) spectroscopy, eventually to investigate how pharmacological and/or immunological manipulations can affect the pathological and psychomotor abnormalities in humans infected with HIV-1. We will also correlate such brain metabolic changes with the degree of dementia in HAD patients. This will be accomplished through he neuropsychological assessment of participants. Thus, a sophisticated array of experimental approaches will be used to define molecular mechanisms underlying the pathophysiology of HAD, which ultimately will be critical for the development and assessment of new therapeutic strategies. There is one specific aim: 1) to test the hypothesis that cerebrospinal fluid (CSF) viral load, CD4+ cells, and/or cytokine content correlates with increases in pH in various regions of the brain, specifically the basal ganglia and cerebellum. In addition, neuropsychological testing will be performed on all subjects enrolled in this study in an effort to a) assess subject neurocognitive/motor status and b) to link the clinical developmental stage of dementia with CSF viral load and brain pH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AUGMENTATION NEUROSURGERY
OF
ACCURACY
FOR
IMAGE-GUIDED
Principal Investigator & Institution: Skrinjar, Oskar; Biomedical Engineering; Georgia Institute of Technology 505 10Th St Nw Atlanta, Ga 303320420 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): The ultimate goal of this work is to increase the success rate of the microelectrode-guided surgery and consequently improve the quality
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of life of patients suffering from movement disorders. To achieve this goal, methods are proposed to augment the navigational accuracy of the surgery without interfering with standard portions of the procedure. To successfully target a specific brain location (e.g. the best location for implantation of a permanent stimulating electrode), one needs to accurately know the boundaries of the neighboring structures of interest (in this case: Basal Ganglia, Thalamus, Sub-thalamus, optic tract). In the standard procedure, these boundaries are obtained from a brain atlas. However, the accuracy of the 3rocedure is adversely affected by: the shape and size difference in anatomy of the brain atlas and of the 3atient, and by intraoperative brain deformation. To address these problems the following aims are proposed: AIM 1. Available brain atlases will be explored and the highest-resolution one will be selected. A method for building 3D surface models of the structures of interest from the atlas images will be designed. The atlas will be represented by its images stacked into a 3D image volume and by a collection of 3D surface models. AIM 2. A highly accurate method for nonrigid alignment of the atlas 3D image and the patient's preoperative MR scan will be developed. This alignment will be applied to the atlas models to adjust their position, shape, and size. This will bring the models into registration with the patient MR scan making them patient specific. AIM 3. The locations of boundaries between structures of interest along the microelectrode tracks are recorded intraoperatively. This information will be used to fine-tune the patient specific models in order to make them more accurate. AIM 4. The intraoperative brain deformation will be analyzed, its affect on the accuracy of the microelectrodeguided surgery will be investigated, and methods for its compensation will be explored. AIM 5. The proposed methods will be clinically tested on 50 cases of microelectrodeguided surgery. Although the proposed methods will be applied to the microelectrodeguided surgery, they can be extended to other image-guided neurosurgical procedures, including tumor removal and epilepsy surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASAL GANGLIA CIRCUITRY IMMEDIATE EARLY GENE EXPRESSION Principal Investigator & Institution: Wirtshafter, Robert D.; Psychology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-DEC-1998; Project End 31-DEC-2003 Summary: (from Abstract) The long term objective of the current proposal is the attainment of a greater understanding of the functional organization of the basal ganglia. Substantial evidence suggests that many neurological and psychiatric disorders, including Parkinson's disease, Huntington's disease, Sydenham's chorea, torsion dystonia, Tourette's syndrome and schizophrenia, may result from abnormalities in the activity of these nuclei. Progress in understanding the etiology of these disorders, and in developing treatments for them, is largely dependent on advances in understanding the basic nature of basal ganglia functioning. The proposed experiments are designed to examine basal ganglia by using the immunocytochemical detection of immediate early genes (IEGs) as markers for neurons affected by various behavioral or pharmacological manipulations. The striatum is the largest nucleus within the basal ganglia and is the primary terminus of input into this system. The first set of studies will examine the pharmacological and behavioral control of IEG expression within this structure with emphasis on the patterning of IEG expression with respect to the striosome/matrix compartmentation of the striatum. The striatum contains a number of neuroactive compounds including dopamine, serotonin, adenosine, acetylcholine and substance P and the role played by these substances in controlling striatal IEG
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expression will be examined. The applicants will also examine the role of dopamine in IEG expression induced by shuttling behavior and characterize the cells that express IEGs under these conditions. Events occurring within the striatum can only influence behavior by affecting the activity of neurons within other parts of the brain. The second group of studies will therefore use IEG expression as a tool to investigate the basic organization of extrastriatal circuitry related to the basal ganglia. Experiments will examine the ability drugs microinjected directly into the striatum, or other basal ganglia nuclei, to influence IEG expression at extrastriatal sites. Other studies will examine the effects of lesions within the basal ganglia on the IEG expression induced by systemic administration of dopaminergic drugs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASAL GANGLIA DISCHARGE PATTERNS IN PARKINSONISM Principal Investigator & Institution: Wichmann, Thomas N.; Associate Professor; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 15-JUN-2001; Project End 31-MAY-2006 Summary: (Verbatim from the Applicant's Abstract) The basal ganglia are part of larger circuit that involves thalamus and cortex. Cortical inputs reach striatum and subthalamic nucleus (STN), and are transmitted via internal pallidal segment (GPi) and substantia nigra pars reticulata (SNr) to influence the activity of thalamocortical neurons. The function of this circuitry is disturbed in Parkinson's disease because of loss of dopamine in the basal ganglia. Besides changes in discharge rates, basal ganglia neurons also develop significant abnormalities in their discharge patterns in parkinsonism. One of the most salient abnormalities is the appearance of synchronized oscillatory discharge in STN, the external pallidum (GPe), GPi/SNr, and frontal cortex (detected by EEG). Available data suggest that this may result from altered activity along the cortex-STN-GPi/SNrthalamocortical route. With a combination of extracellular basal ganglia recordings and EEG, the proposed primate experiments explore the relationship between oscillatory activity in cortex and basal ganglia and will test the hypothesis that oscillatory discharge in the cortex-basal ganglia circuitry contributes to parkinsonism. The correlation studies under specific aim (S.A.) 1 assess the link between neuronal discharge in the basal ganglia (GPe, STN GPi, SNr) and EEG with simultaneous recordings in both brain regions. The importance of striatal or extrastriatal dopamine loss for the development of oscillatory discharge in parkinsonism will be tested under S.A. 2 by studying changes in oscillatory activity in basal ganglia and cortex induced by microinjections of the dopamine receptor agonist apomorphine at striatal and extrastriatal basal ganglia sites in parkinsonian animals. The experiments under S.A. 3 will test whether blockade of glutamate receptors in STN (blocking corticosubthalamic inputs) reduces oscillatory activity in basal ganglia and cortex. Finally (S.A. 4), the hypothesis will be tested that synchronized oscillatory discharge in the basal ganglia, induced by electrical stimulation of STN with bursts of stimulation pulses at burst rates between 2 and 30 Hz, disrupts motor performance and induces parkinsonian motor abnormalities in normal monkeys. These studies will help to understand the significance of oscillatory discharge in the basal ganglia and cortex in parkinsonism. This may provide guidance in the development of drug treatments directed at normalizing abnormal discharge patterns, and may help to understand the mechanism of action of existing treatments for Parkinson's disease, including dopamine receptor agonists, glutamate receptor antagonists, and deep brain stimulators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BASAL GANGLIA EXPRESSION OF TORSINA IN TRANSGENIC MICE Principal Investigator & Institution: Ehrlich, Michelle E.; Professor of Neurology; Neurology; Thomas Jefferson University Office of Research Administration Philadelphia, Pa 191075587 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): Early-onset dystonia (DYT1) is caused by an autosomal dominant mutation in the torsinA protein. Dystonia is manifested by sustained muscle contractions, appearing as movements or abnormal postures, which may be focal or diffuse. TorsinA expression is diffuse within both the central nervous system and peripheral organs. Therefore, similar to many other neurologic diseases, it is important to determine how a diffusely expressed protein can cause localized disease. In the case ofdystonia, extensive evidence points to a key, although not necessarily unique, dysfunction within the basal ganglia. With recent progress in this laboratory in the identification ofa striatal specific promoter active in transgenic mice, along with the expertise of collaborators, this group of investigators is in a unique position to test hypotheses regarding the role of the basal ganglia in dystonia. Simultaneously, testing of these hypotheses may lead to valuable animal models of the disease. This is an R21 proposal to create these transgenic models. Specific Aim 1 is to create transgenic mice expressing mutated human torsin A in the l) substantia nigra, under the direction of the human tyrosine hydroxylase promoter and 2) in the striatum, under the direction of the mouse DARPP-32 promoter. SPECIFIC AIM 2 is to initiate the analysis of these mice, and to determine whether selective expression of torsinA in the substantia nigra and/or striatum results in 1) a movement disorder in transgenic mice, as determined by rotarod testing and/or 2) abnormalities ofdopaminergic neurotransmission in the striatum, as determined by induction of c-los expression following administration ofa psycho stimulant, i.e. a dopamine agonist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BASAL GANGLIA FUNCTION IN OBSESSIVE COMPULSIVE DISORDER Principal Investigator & Institution: Rauch, Scott L.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: The goals of this project are to test specific hypotheses about the pathophysiology of obsessive compulsive disorder (OCD) using functional MRI (fMRI) and cognitive neuroscience methods. The basal ganglia have been implicated in the pathophysiology of OCD and also in the normal mediating anatomy of implicit (i.e., nonconscious) learning. We have developed an fMRI paradigm to measure activity within components of the basal ganglia during the performance of an implicit learning task. In preliminary functional imaging studies, we have observed an abnormal activation profile in medication-free subjects with current OCD. Specifically, in comparison to normal control subjects, patients with OCD exhibit a failure to activate right striatum, and an absence of thalamic deactivation, as well as aberrent medial temporal activation (i.e., not found in normal subjects). These results are consistent with evolving neurobiological models of OCD and basal ganglia function. The current proposal aims to: 1) use this fMRI paradigm to replicate and elaborate upon the above findings in a larger cohort of medication-free patients with active OCD and matched normal comparison subjects; 2) determine the specificity of the findings in OCD by
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studying psychiatric comparison subjects; and 3) further investigate the neuropsychological consequences of the abnormal activation profile observed in OCD. It is anticipated that this approach will yield new information regarding the pathophysiology of OCD and related disorders, while providing new insights about the normal function of the basal ganglia and the mediating anatomy of normal learning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BASAL GANGLIA FUNCTION--BASIC MECHANISMS AND EFFECTS Principal Investigator & Institution: Assad, John A.; Assistant Professor; Neurobiology; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: The basal ganglia (BG) are a set of subcortical nuclei that play a crucial role in the control of voluntary movements. Their importance is underscored by diseases of the BG, such as Parkinson's disease, which compromise the initiation and execution of voluntary movements. While much is known about the general organization of the BG, fundamental questions remain about their role in the normal control of movement. These questions are particularly relevant given the renewed interest in restorative neurosurgical procedures, such as chronic electrical stimulation. that target the BG to relieve Parkinsonian symptoms. The main goal of this is to understand the role of the BG in the normal control of movement, using the awake behaving macaque monkey as an experimental system. The first aim addresses an intriguing paradox about the BG: while diseases affecting the BG cause problems with initiating voluntary movements, most neurophysiological studies have found that neuronal activity in the BG occurs too late to play a role in movement initiation. However, in most of these studies the movements were in response to an external sensory stimulus. There is evidence from Parkinsonian patients that stimulus-cued movements are less severely affected than selfinitiated movements. We will thus examine whether the BG play a special role in selfinitiated movements - self-initiated with respect to either when a movement is made or which movement is made. The second aim addresses the roles of the direct and indirect BG pathways. The output of the BG is influenced by two distinct pathways with opposing effects on movement: a direct pathway from the striatum which facilitates movement, and an indirect pathway via the subthalamic nucleus (STN) which inhibits movement. While the identification of these pathways has provided a useful framework for understanding movement disorders, many questions remain about their roles in normal movement. We will test one hypothesis, that the two pathways may act in concert to "select" a specific movement among competing possibilities of movement, by examining how neurons in the output nuclei of the BG are affected by electrical inactivation of the STN. For this purpose, it will be necessary to examine the neuronal effects of electrical stimulation in the STN. Little is known about the neuronal effects, even though STN stimulation is now being used to treat Parkinsonian symptoms in human patients. We will directly measure the neuronal effects of electrical stimulation in the STN, and examine how these effects vary with the parameters of stimulation. For this we will develop and test new multielectrode techniques for recording from and electrically stimulating multiple deep brain sites simultaneously. The combined basic studies and technical innovations will increase our understanding of the role of the BG in normal movement and movement disorders, and will hopefully provide new approaches for treating Parkinsonian conditions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BASAL GANGLIA NEUROPHYSIOLOGY DURING DBS IN RATS Principal Investigator & Institution: Chang, Jing-Yu; Assistant Professor; Physiology and Pharmacology; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-JUL-2007 Summary: (provided by applicant): Parkinson's disease (PD) is a degenerative neurological disorder affecting millions of patients all around the world. Renewed use of the deep brain stimulation (DBS) method provides a new opportunity for treating PD. A key issue to improve the treatment is to fully understand the neural mechanisms underlying the therapeutic effects of DBS. In this proposed study, two unique techniques developed in our laboratory: the chronic multiple-channel single unit recording and rat model of DBS, will be employed to study the neural responses in multiple basal ganglia regions during behaviorally effective DBS in rat model of Parkinsonism. A first objective is to establish a rodent model of DBS in Parkinsonian conditions. The effects of DBS will be evaluated in dopamine lesioned rats performing treadmill locomotion and limb use asymmetry tests. Locomotor d deficits during treadmill walking and imbalance usage of forelimb in vertical exploratory behaviors will develop after unilateral dopamine lesion. High frequency stimulation (HFS) of the subthalamic nucleus (STN) and the substantia nigra pars reticulata (SNr) will then be applied to alleviate these motor abnormalities. The degree of dopamine depletion in the basal ganglia will be detected by immunohistochemical staining of dopamine marker and this result will be correlated with the severity of motor deficits and DBS effects. Second, the basal ganglia neural responses following a dopamine lesion and during behaviorally effective HFS will be examined. Single neural activity and local field potential in the striatum globus pallidus, STN and SNr will be recorded simultaneously in a 64 channel recording system in the rat performing these behavioral tests. Neural responses following dopamine lesion will help us to understand the pathophysiologic process of developing Parkinsonian syndromes while the neural responses during behaviorally effective HFS will shed light on how DBS can restore normal information processing in the basal ganglia neural circuits that are disrupted following dopamine lesion. Several important improvements on recording and stimulation techniques will be made in cooperation with Biographic Inc. to achieve optimal conditions for high frequency stimulation and artifact free recording. The goal of this study is to explore the basic neural mechanism underlying the therapeutic effects of DBS and the knowledge obtained form this study will help us to improve the clinical treatment of PD with DBS method. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BLOOD FLOW CHANGES AND ANTIPSYCHOTIC DRUG ACTION Principal Investigator & Institution: Lahti, a C.; Psychiatry; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2002; Project Start 01-MAY-1999; Project End 31-JAN-2003 Summary: (adapted from applicant's abstract): Antipsychotic drugs reduce psychosis, induce motor effects, and have miscellaneous other actions. The brain substrates of these effects, beyond actions on receptor populations are poorly understood. The investigator proposes to determine the dynamic time course of the effects of antipsychotics on regional cerebral blood flow (rCBF) using PET and 15OH2 in drug-free schizophrenia patients as a direct pharmacodynamic assessment of drug action in the human brain. rCBF measurements would span the pharmacokinetic time course. The investigator proposes to characterize the dynamic time course of rCBF alterations following the acute
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and six days of administration of two different antipsychotic drugs, the traditional antipsychotic haloperidol and the newer antipsychotic olanzapine. The ability of the changes in rCBF following acute and subacute antipsychotic administration to predict subsequent treatment response would also be evaluated. Based on their preliminary findings, the investigators hypothesize that acute and subacute drug-induced rCBF changes in selected regions will predict treatment response for positive symptoms (anterior cingulate and medial frontal cortex), for negative symptoms (middle frontal cortex and inferior parietal cortex), and motor side effects (basal ganglia). The proposed subacute drug administration regimen would approximate a pharmacokinetic steady state for both antipsychotics. An additional aim of the proposal is to compare the rCBF changes induced by haloperidol versus olanzapine during the scanning sessions obtained with acute and subacute (steady state) antipsychotic administration. The investigator proposes that the pattern of activation in the basal ganglia will best discriminate the two antipsychotic agents. These studies will hopefully provide rCBF correlates of antipsychotic activity. This information will allow the development of hypotheses related to drug mechanism of action, as well as potential surrogate markers of drug action. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHEMOTHERAPY FOR HUNTINGTON'S DISEASE Principal Investigator & Institution: Hersch, Steven M.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2003; Project Start 15-APR-2003; Project End 31-MAR-2008 Summary: Transcriptional modulation is a promising approach to neuroprotection in Huntington's disease (HD). Our preliminary data indicates that transcriptionally active compounds like histone deacetylase (HDAC) inhibitors and aureolic acid antibiotics including mithramycin are among the most promising potential treatments available for HD. Phenylbutyrate is the HDAC inhibitor most developed for human use and with the best evidence for brain bioavailability. Mithramycin is used to treat Paget's disease, several types of malignancy, and hypercalcemia of malignancy and has the greatest efficacy in HD transgenic mice to date. The safety, tolerability, and efficacy of these agents is completely unknown in HD or other neuro-degenerative disorders. This project will test the feasibility of these medications in HD in large scale trials of efficacy. In aim one, we will examine whether phenylbutyrate is safe and tolerable for use in HD patients and whether it can improve any symptoms or biological markers of HD. A randomized double-blind placebo-controlled long-term safety and tolerability trial of phenylbutyrate in HD patients will be performed. We will assess the impact of phenylbutyrate treatment on: standardized clinical ratings of motor function, cognition, behavior, and functional capacity. We will also examine In vivo markers of neurodegeneration and transcriptional modulation including proton magnetic resonance spectroscopy for lactate and NAA, and peripheral markers of transcriptional modulation, histone acetylation, and phenylbutyrate activity. In aim two, we will examine whether mithramycin is safe and tolerable in long-term use in HD patients and whether it can improve any symptoms or biological markers of HD. Following an open label dose-ranging trial in which a maximally tolerated dose will be determined, subjects will be randomized into a double-blind placebo controlled safety and tolerability trial of mithramycin using intermittent infusion. We will also assess the impact of mithramycin treatment on; standardized clinical ratings of motor function, cognition, behavior, and functional capacity. We will examine In vivo markers of
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neurodegeneration including proton magnetic resonance spectroscopy of the basal ganglia and cortex, and peripheral markers of mithramycin activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHRONIC ALTERATIONS IN RESPONSE TO GLUTAMATE,GABA, DOPAMINE
ELECTROPHYSIOLOGICAL
Principal Investigator & Institution: Levine, Michael S.; Professor; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2003 Summary: The hypothesis to be examined in this project is that loss of nigrostriatal dopamine (DA) neurons in Parkinson's disease (PD) and in animal models of PD1 as well as the pharmacological and surgical treatments of PD alter the functional characteristics of glutamate, Y-amino butyric acid (GABA) and DA receptors in subthalamic nucleus (STN) neurons. The STN has become important for understanding changes in basal ganglia function in PD since it is clear that one outcome in PD is a marked change in the activity of STN neurons. The current model of why STN neuronal activity changes is based on the hypothesis that DA loss in PD leads to a release of the STN from tonic inhibition by the extemal pallidurn. Increased activity of the STN, the only excitatory projection nucleus in this systern1 then provides the major excitatory drive onto basal ganglia outputs. There is a growing consensus that this model of PD is unsatisfactory. Thus, this project is aimed at examining other alternatives. We will use in vifm electrophysiology in STN slices to examine changes in receptor function after unilateral DA depletion and after three treatment paradigms, the classic, chronic LDOPA treatment, the recent approach of deep brain stimulation of the STN, and a novel approach of implanting GABA-producing cells into the STN. There are four aims that will test our central hypothesis. Aim I will determine if DA depletion alters responses mediated by activation of specific glutamate receptor subtypes and GABA receptors in STN neurons. Aim II will determine if DA depletion alters subsequent DA modulation of responses mediated by activation of specific glutamate receptor subtypes and GABA receptors in STN neurons. Aim III will test the hypothesis that treatment with L-DOPA after DA depletion restores normal responses to the activation of glutamate, GABA/A and DA receptors in the STN. Aim IV will test the hypothesis that implantation of cells that produce excess GABA in STN or deep brain stimulation of STN after DA depletion (two procedures that silence STN neurons) alter abnormal responses induced by activation of glutamate, GABA/A, and DA receptors in either the entopeduncular nucleus (homologue of the internal pallidal segment of primates) and/or the substantia nigra pars reticulata. The results from this project, combined with those from Projects 1 and 3, will provide a more complete understanding of the mechanisms underlying changes in STN neural activity to design new, rational pharmacotherapies for PD that can use the STh as a therapeutic target. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITIVE SEQUELAE OF METHAMPHETAMINE ABUSE Principal Investigator & Institution: Salo, Ruth E.; Psychiatry & Behavioral Sciences; University of California Davis Sponsored Programs, 118 Everson Hall Davis, Ca 956165200 Timing: Fiscal Year 2003; Project Start 15-SEP-2003; Project End 31-MAY-2006 Summary: (provided by applicant): This application is to support a period of advanced training in multidisciplinary approaches to the study of substance abuse with a focus on
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methamphetamine [MA]. The candidate will acquire new knowledge in the fields of addiction psychiatry, pharmacology, neuroanatomy and neuropsychological assessment, providing the foundation to develop an independent research program that will examine the cognitive and neural sequelae of stimulant abuse. Additional training is needed to achieve this goal, as the study of substance abuse is new to the candidate and requires specialized knowledge related to the substances themselves as well as the behavioral results of long-term abuse. The candidate will work with a small group of talented mentors who will provide a solid background in addiction medicine, neurological research and cognitive assessment of substance abusers. The candidate will attend advanced courses in pharmacology, neuroanatomy, and participate in clinical rotations at substance abuse clinics (yrs 1-3) and neurobehavioral clinics (4-5). UC Davis is uniquely suited for the training and research goals of the candidate. The UC Davis School of Medicine offers advanced courses in pharmacology, neuroanatomy and clinical rotations, and staffs an ongoing program of neurobehavioral rounds and MRI/CT scan reading. The candidate's immediate goal is to assess cognitive performance in a group of MA dependent subjects, substance abusing controls, and focal lesion patients compared to healthy controls and to correlate the cognitive data with clinical symptomatology associated with substance abuse. The candidate will employ a focused battery of cognitive tasks that have been validated as measures of frontostriatal functioning and are believed to recruit the anterior cingulate [ACC], prefrontal cortex [PFC] and the basal ganglia, brain regions noted to be damaged following long-term MA abuse. This project will complement ongoing imaging studies of neural damage in stimulant abusers at UC Davis. The specific aims of the research proposed in this project are to measure: 1) the ability to suppress response conflict; 2) cognitive flexibility; 3) explicit and implicit memory processes; and 4) to correlate the cognitive findings with clinical symptomatology associated with stimulant abuse. The candidate's long-term career goal is to use the experience gained during this award to develop an independent research program that applies the approaches of cognitive neuroscience and clinical neuropsychiatry to the study of substance abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTINUITY OF LIMBIC CIRCUIT THROUGH THE BASAL GANGLIA Principal Investigator & Institution: Haber, Suzanne N.; Anatomy and Neurobiology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-1989; Project End 31-MAR-2008 Summary: (provided by applicant): Mental disorders, including schizophrenia, obsessive compulsive disorder (OCD) and drug addiction are linked to pathology in the prefrontal cortico-ventral striatal-thalamic circuit by imaging studies, post mortem anatomical studies, and basic research. Not only do these illnesses have a common circuitry, but they all emerge relatively early in life, primarily during adolescence or young adulthood. Anatomical, physiological and pharmacological studies in this circuit have been central in gaining insight into the mechanisms underlying mental health disorders. The structures involved include the prefrontal cortex, the ventral striatum (VS), the ventral pallidum/substantia nigra, pars reticulata (VP/SNr), and the medial dorsal N. of the thalamus (MD), which links the circuit back to cortex. During the previous funding period we: 1. defined the territory of the VS in primates, 2. identified important and unique cellular features of the VS, including BCL-2 positive cells and newly formed cells from the subventricular zone, and 3. identified the afferent connections to the midbrain dopamine. We also demonstrated a mechanism by which
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the limbic component of the basal ganglia impacts on other basal ganglia circuits through striato-nigro-striatal pathways. Finally, place of the thalamus in cortical regulation emphasizes newer concepts in control of cortico-cortical activity through its complex connections. We showed that an integrative network exists for the dorsal basal ganglia through its thalamic projections to different cortical layers and through a nonreciprocal cortico-thalamic projection. The general hypothesis of this proposal is that the combination of the impact of the ventral BG thalamocortico-thalamic network several cortical areas along with the unique cellular features of the ventral striaturn place this circuit in a position to be particularly vulnerable during adolescence. The experiments proposed here will test this hypothesis by: 1. delineating the thalamo-cortical network to determine how pathways through the ventral BG circuit can both reinforce its own loop and also impact on other cortical areas and BG circuits; 2. characterize bcl-2-positive neurons and newly formed cells and determine whether the unique cellular characteristics of the VS differ during adolescence, and whether they are particularly vulnerable to stimulation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTRIBUTION OF NEURAL MEMORY CIRCUITS TO LANGUAGE Principal Investigator & Institution: Ullman, Michael T.; Associate Professor; None; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-MAY-2005 Summary: The long-term objective of this project is to understand the brain bases of the mental lexicon, which contains memorized words, and the mental grammar, which contains rules that combine lexical forms into larger words, phrases, and sentences. We propose that the memorization and use of words is subserved by temporal-lobe circuits previously implicated in the learning and use of fact knowledge, whereas the acquisition and use of grammatical rules is subserved by frontal/basal-ganglia circuits previously implicated in the learning and expression of motor, perceptual, and cognitive "skills," such as riding a bicycle. Thus we posit that lexicon and grammar are linked to distinct brain systems, each of which is domain-general in that it subserves nonlanguage as well as language domains. This novel view contrasts with the two main competing theoretical frameworks. Although we share the perspective of traditional dual-system theories in positing that lexicon and grammar are subserved by distinct systems, we diverge from these theories where they assume components dedicated (domain-specific) to each of the two capacities. Conversely, while we share with singlesystem theories the view that the two capacities are subserved by domain-general circuitry, we diverge from them where they link both capacities to a single system with broad anatomic distribution. To distinguish our theory from the other two, we will probe the brain bases of irregular and regular word transformations, in which lexicon and grammar can be contrasted, while other factors are held constant. Irregular forms (e.g., dig-dug) are retrieved from memory, whereas regular forms (e.g., look-looked) require a suffixation rule. We predict, and have found in our preliminary studies, links among irregulars (lexicon), facts, and temporal- lobe circuits, and among regulars (grammar), skills, and frontal/basal-ganglia circuits. Single-system models do not make this set of predictions, and traditional dual-system theories do not predict the links with fact and skill use. Patients with either temporal-lobe or frontal/basal-ganglia damage will be given tasks probing the production and judgment of irregular and regular past tense inflection, plural inflection (mice, bees), and derivational morphology (solemnity, awkwardness), as well as measures of fact and skill use. Our specific aims are to test three hypotheses by probing for double dissociations between irregulars and regulars,
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and between facts and skills: (1) Lexicon is linked to temporal-lobe circuits, and grammar to frontal/basal-ganglia circuits. (2) These circuits also subserve fact and skill use, respectively. (3) The basal ganglia play a similar role in motor activity and grammatical rule use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROL OF SPIKING IN BASAL GANGLIA OUTPUT NEURONS Principal Investigator & Institution: Jaeger, Dieter; Assistant Professor; Biology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 10-APR-2000; Project End 31-MAR-2005 Summary: (Adapted from the Investigator's Abstract): The objective of the proposed research is to determine how the activity of neurons in the substantia nigra pars reticulata (SNr), one of the major output nuclei of the basal ganglia, is controlled by synaptic input. Simple network models of basal ganglia function and disorders assume that the activity of output neurons is determined by summing the amount of inhibitory and excitatory inputs received. It is clear, however, that single neurons have active intrinsic mechanisms by which synaptic inputs may be integrated in a highly complex non-linear fashion. These complex properties of synaptic integration will be examined in SNr neurons by combining in vitro whole cell recording, extracellular recording and computational modeling. First the passive and then the active properties of these neurons will be catalogued using whole-cell recordings in rat brain slices. These experiments will use current and voltage-clamping in conjunction with pharmacological blockade of various voltage- and ligand gated channels to isolate and characterize purely passive membrane properties and specific voltage-dependent conductances. Recorded neurons will be intracellularly stained and reconstructed histologically with Neurolucida, and the quantitative morphometric data obtained will be used along with the electrophysiological data to construct a compartmental model of SNr neurons. The model will be adjusted and fine tuned by comparing the behavior of the model to that of SNr neurons in whole cell recordings in vitro and in extracellular single unit recordings in vivo, while constraining the parameters to those obtained in the recording experiments. To study the mechanisms by which synaptic input controls activity, the parameters of synaptic inputs including the time courses and amplitudes of excitatory and inhibitory inputs will be measured and used in the model. Finally, realistic sequences of synaptic input, inferred from in vivo and in vitro recordings of SNr neurons will be input to the model to determine the input-output function of SNr neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DECREASED MOTOR THRESHOLDS IN DYSTONIA Principal Investigator & Institution: Blood, Anne J.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 05-APR-2004; Project End 31-MAR-2006 Summary: (provided by applicant): This is an application for an NINDS Exploratory / Developmental Grant (R21), entitled "Decreased Motor Thresholds in Dystonia." The goal of this project is to begin comparing the relative contributions of the motor and somatosensory systems to dystonic pathology by measuring brain activity in focal hand dystonic patients during motor and somatosensory tasks, working toward a hypothesis that the motor system plays a more primary role than the somatosensory system in dystonia. Specifically, we will make precise anatomical distinctions between motor and
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somatosensory cortical regions in our analysis of brain activity measured in dystonic patients during simple finger-tapping and finger-stimulation tasks (Aim 1). We will also use perfusion MRI and hemodynamic response timecourses to address some basic questions about "resting" activity in focal hand dystonic patients, both to guide our experimental design, and to potentially demonstrate how motor task repetition may lead to increased resting activity in dystonia (Aim 2). Finally, we will begin to develop tasks that engage the motor and somatosensory systems near activity threshold, with an overall aim of finding new ways of detecting patient/control differences in motor and somatosensory activity, and with a specific hypothesis that motor activity thresholds may be decreased in focal hand dystonia (Aim 3). In the future, we will use these tools to assess how botulinum toxin and other treatments of the disorder influence brain motor and somatosensory abnormalities, both in the short- and long-term. The proposed studies are expected to generate novel insights into neural mechanisms of dystonia, and eventually lead to significant improvements in the treatment of this debilitating disorder. The motor/somatosensory comparisons and "resting" activity measurements will allow us to gain new information about the relative roles of motor and sensory systems in dystonia, and increase the precision and accuracy of information gained from this and future brain imaging studies of this disorder. The "motor threshold" tasks are expected to provide evidence for decreased motor thresholds in dystonia that extend beyond primary motor cortex. Understanding the relative roles of motor and somatosensory systems in dystonic pathology will be a crucial step in determining which of the existing treatments for the disorder are most successful, and will allow us to better target new treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEEP BRAIN STIMULATION IN PARKINSON'S MODELS Principal Investigator & Institution: Anderson, Marjorie E.; Professor; Rehabilitation Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Although high-frequency deep brain stimulation (HF-DBS) in the globus pallidus or subthalamic nucleus has become a common technique used to treat drug-resistant symptoms of Parkinson's disease, the mechanisms by which HF-DBS exerts its effects are unknown. In the proposed studies, the ability of chronic administration of the insecticide rotenone, to produce an animal model of Parkinson's disease will first be tested in monkeys. Using PET imaging now available in the University of Washington Regional Primate Research Center, changes in dopamine innervation after administration of rotenone will be measured using a marker of the monoamine vescicular transporter that is present in dopaminergic nerve terminals. These changes will then be correlated, over time, with changes in behavior and with electrophysiological changes in the rate and pattern of discharge of neurons in basal ganglia-receiving areas of the thalamus. This model will then be used to couple the electrophysiological effects of HF-DBS, which can be recorded from basal gangliareceiving neurons of the thalamus, to the stimulation-induced changes in regional metabolism in the cortex and thalamus. PET imaging with the metabolic marker, [8-F] flurodeoxyglucose (FDG), will be used to measure metabolism. This technique has generally shown a relative hypermetabolism in the globus pallidus and thalamus of humans with Parkinson's disease and a relative hypometabolism in areas of the frontal cortex. Changes reported to be induced by HF-DBS have been mixed however. The combination of electrophysiology and metabolic imaging will allow us to address some of the discrepancies from the human literature. Special attention will be paid to the
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development of abnormal patterns of bursting behavior in the thalamus of monkeys treated with rotenone, as well as the effect of HF-DBS on burst behavior. This will test the hypothesis that some of the symptomatology of Parkinson's disease, and its relief using HF-DBS, is a consequence of abnormal patterns of activity in basal gangliathalamic-cortical circuits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINE D2 AND ADENOSINE A2A ROLES:TREMULOUS MOVEMENTS Principal Investigator & Institution: Salamone, John D.; Professor; Psychology; University of Connecticut Storrs Unit 1133 Storrs-Mansfield, Ct 06269 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Symptoms of parkinsonism, such as akinesia, bradykinesia, and tremor, can be caused by degeneration of dopamine (DA) neurons, or by administration of DA antagonist drugs. Parkinsonism is characterized by a cascade of neurochemical events that reflect interactions between several neurotransmitters in the circuitry of the basal ganglia, including DA, acetylcholine, serotonin, GABA and adenosine. Within the last few years, increasing evidence has accumulated indicating that central adenosine neurons play an important role in modulating the functional circuitry of the basal ganglia. Several subtypes of adenosine receptors are involved in motor function, and anatomical studies have demonstrated that the adensonine A2A receptor subtype has a relatively high degree of expression within the striatum. Although several types of striatal cells contain some adensonine A2A receptors, these receptors are present in very high densities on striatopallidal neurons, which also tend to co-express DA D2 receptors and enkephalin. It has been suggested that antagonists of adenosine A2A receptors could have some potential utility as antiparkinsonian drugs. In a recent study from our laboratory, it was demonstrated that IP injections of the adenosine A2A antagonist, KF17837, also suppressed haloperidol-induced tremulous jaw movements, and reversed the locomotor suppression induced by this D2 antagonist. This profile of activity is consistent with the hypothesis that antagonism of adenosine A2A receptors can result in antiparkinsonian effects in animal models. The proposed experiments are designed to investigate the role of the striatopallidal GABAergic pathway as a possible mediator of the putative antiparkinsonian effects of adenosine A2A antagonists. These proposed studies will focus on the tremulous jaw movement model, which is related to parkinsonian tremor. It is hypothesized that adenosine A2A antagonists are acting on striatopallidal GABAergic neurons that also express DA D2 receptors. In view of research showing that haloperidol increases extracellular GABA in globus pallidus, and that haloperidol-induced tremulous jaw movements are reduced by pallidal injections of bicuculline, it is hypothesized that doses of adenosine A2A antagonists that reduce jaw movement activity also will reduce haloperidol-induced increases in GABA release in globus pallidus. In addition, it is hypothesized that adenosine agonists and antagonists will interact to regulate the behavioral and neurochemical effects of haloperidol. These hypotheses will be investigated using studies that involve both systemic and intrastriatal injections of drugs that act upon A2A receptors, and the proposed work will involve a combination of behavioral pharmacology and microdialysis methods. This research is designed to enhance our understanding of the neurotransmitter interactions that are involved in the generation of tremulous movements, and to foster the development of new drugs for the treatment of parkinsonism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE MODULATION OF LIMBIC CORTICOACCUMBENS SYSTEM Principal Investigator & Institution: Onn, Shao-Pii; Neurobiology and Anatomy; Drexel University College of Medicine 245 N 15Th St Philadelphia, Pa 19102 Timing: Fiscal Year 2002; Project Start 09-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's Abstract) Psychostimulant abuse in humans is known to produce states similar to both positive and negative symptoms of schizophrenia. Studies in rats have suggested that hyper-dopaminergic activity in subcortical structures such as nucleus accumbens leads to behavioral abnormality that may have relevance to positive symptoms. Emotional and cognitive deficits that characterize negative symptoms have been recently demonstrated in monkeys similarly treated with low doses of amphetamine and that in many ways resemble those identified in human amphetamine abusers. These cognitive deficits are believed to result from a dysfunction in the prefrontal cortex, thus linking to a clinical state of hypofrontality. A basic dysfunction of prefrontal-accumbens circuits is thought to be critical to the cognitive dysfunction, negative affect and abnormal reward-related behavior that is characteristic of schizophrenia and drug abuse. My working hypotheses is that in amphetamine treated rats there exists deficits in the excitatory drive from the limbic afferents from the entorhinal cortex and the mediodorsal thalamus to the prefrontal cortex and/or deficits in the dopamine modulation of these excitatory afferents. Thus the proposed experiments using in vivo intracellular recording and labeling techniques will compare and contrast information arising intracortically (eg entorhinal cortex; aim 1) and subcortically (eg mediodorsal thalamus; aim 2), the latter of which transmits basal ganglia outflow back to the prefrontal cortex. Lastly cortical processing in influencing basal ganglia outflow from the nucleus accumbens. I predict attenuated intracortical processing (aim 1) to occur in conjunction with an augmented basal ganglia feedback circuit, as marked by increases in both mediodorsal thalamusevoked activity in prefrontal cortex neurons (aim 2) and prefrontal cortex-evoked activity in nucleus accumbens neurons (aim 3), in amphetamine treated rats. The proposed study is of particular interest with respect to the deficit syndrome in schizophrenia and possibly other mental disorders such as drug addiction associated with negative affect and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOPAMINE REGULATION IN PARKINSONIAN RAT BY GENE THERAPY Principal Investigator & Institution: Kang, Un Jung.; Associate Professor; Neurology; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2002; Project Start 01-AUG-1993; Project End 31-MAR-2007 Summary: (provided by applicant): L-3,4-dihydroxyphenylalanine (L-DOPA) is the mainstay of therapy for Parkinson's disease (PD). Chronic L-DOPA therapy is limited, however, by the development of motor response complications, such as progressively shorter duration of improvement in akinesia (wearing-off) and the appearance of LDOPA-induced abnormal involuntary movements. Innovative methods of sustained and localized central nervous system (CNS) dopamine delivery may further optimize LDOPA therapy. Such methods are being explored clinically by CNS transplantation studies with fetal dopaminergic neurons and experimentally by neuronal stem cell implants and gene therapy. Our studies during the past funding cycles have defined optimal sets of genes necessary for dopamine replacement using ex vivo gene therapy
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using genetically modified fibroblasts. We also developed rat behavioral models that are relevant to the akinesia of PD patients. Using akinesia behaviors, we have noted that lesion severity has a major influence on the shortening of the response duration with minor contribution by the chronic intermittent L-DOPA therapy. Therefore, studies proposed in this continuing renewal application will determine the optimal parameters of gene therapy to improve akinesia and minimize and prevent motor response complications. We will use adeno-associated virus vectors to deliver tyrosine hydroxylase and guanosine triphosphate (GTP) cyclohydrolase 1 genes. The optimal combination of anatomical targets for gene therapy to improve akinesia will be defined by examining the effects of gene therapy delivered to basal ganglia structures, such as subthalamic nucleus, substantia nigra par reticulata, that receive dopaminergic inputs, in addition to the striatum. The optimal timing to initiate dopamine replacement gene therapy to forestall development of motor response complications will also be examined. These results will have significant implications beyond dopamine replacement gene therapy proposed here and guide other therapies such as fetal dopaminergic cell transplantation, neurotrophic factor therapy, stem cell therapy, and other CNS targeted delivery systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINERGIC AND BASAL GANGLIA PLASTICITY IN AGING Principal Investigator & Institution: Mcneill, Thomas H.; Professor; Neurogerontology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-JUN-1991; Project End 31-MAY-2003 Summary: A basic knowledge of how we age is essential for our understanding of agerelated impairments in brain function that lead to major personal and economic problems for older citizens. In addition, changes in the brain considered part of normal aging may contribute to the onset and progression of age-related neurodegenerative diseases of the central nervous system (CNS), the classic examples of which are Alzheimer's, Huntington's and Parkinson's diseases. However, while many of the neurodegenerative diseases of the CNS have a characteristic age of onset after midlife, it is unclear what role age-related changes in the morphological, biochemical and electrophysiological properties of CNS neurons play in the onset and progression of a disease process. The proposed program project targets this gap in our knowledge of the aging brain by testing hypotheses about mechanisms of age-related changes in brain function. We propose an integrated program of basic research to examine the cellular and molecular mechanisms involved in brain aging, with particular emphasis on the substantia nigra and striatum, structures especially vulnerable in Parkinson's and Huntington's diseases. The study of reactive synaptogenesis, neuron death and functional adaptability to aging and injury represent the main areas of focus on our renewal application. Furthermore, we propose to manipulate age-related changes in dopaminergic function using chronic dietary restriction or treatment with the dopamine agonist pergolide. These studies will investigate the cellular and molecular events associated with oxidative stress in aging, with an emphasis on GFAP expression and other glial responses that we have documented in response to neurodegeneration. In addition, we will analyze the expression of several recently discovered genes, including apoJ, SCG-10, BDNF, GDNF, which seem to play key roles in processes determining cell survival and plasticity. The proposed experiments will help to understand the cellular and molecular mechanisms that lead to cell death in some regions of the aged brain and will provide the basis for the development of future therapeutic strategies aimed at the treatment of age-related neurodegenerative diseases of the CNS.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOPAMINERGIC MODULATION OF WORKING MEMORY IN PD Principal Investigator & Institution: Hershey, Tamara G.; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 31-MAY-2006 Summary: (provided by applicant): The applicant is a clinical neuropsychologist with graduate training in neuropsychology and postdoctoral training in neuropharmacology and positron emission tomography (PET). The goal of this career development award is to integrate and advance these two areas of interest to answer questions about the neuropharmacological and neurophysiological basis of cognitive dysfunction in movement disorders such as Parkinson's disease (PD). This award will provide the applicant with training in the technical and theoretical issues related to using cognitive and pharmacological activation techniques in functional magnetic resonance imaging (fMRI). Long-term objectives are to address questions about the neural basis of cognitive dysfunction in movement disorders related to dopaminergic and/or basal ganglia dysfunction, such as PD, Tourette's syndrome and Huntington's disease. In addition, questions about the effects of dopaminergic treatments for these and other disorders (e.g. dystonia) on cognitive and neurophysiological functioning are also of interest. Cognitive dysfunction in these diseases, either due to the disease process itself or its treatments, can be limiting and disabling. Understanding the neurophysiologic basis for these symptoms may aid in assessing the effectiveness of current treatments or in developing better treatments. During the award period, the applicant will develop expertise in the use of fMRI, cognitive and neuropharmacological techniques to study these disorders, and will continue to hone her clinical skills in the neuropsychological assessment of movement disorders. The applicant will apply these new techniques to investigate the role of dopamine in working memory. The specific aims of the proposed studies are to test the hypothesis that 1) PD affects prefrontal cortex involvement in working memory and 2) dopaminergic modulation of working memory primarily occurs due to changes in lateral prefrontal cortical activity. To test these hypotheses, the applicant will first perform a behavioral study examining the effects of a steady-state infusion of levodopa, a dopamine precursor, on verbal and spatial working memory in PD patients and controls. The results of this study will then guide the choices of working memory tasks for an fMRl study. Subjects will be asked to perform working memory tasks before and during a steady-state infusion of levodopa. Modulation of the lateral prefrontal cortex is predicted during levodopa infusion. The degree of modulation is predicted to depend on baseline dopaminergic status (PD vs control) and the degree of memory load (low vs high). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DYNAMIC MACAQUE BASAL GANGLIA SACCADE NETWORKS Principal Investigator & Institution: Graybiel, Ann M.; Professor; Brain and Cognitive Sciences; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 04-AUG-2000; Project End 31-MAY-2005 Summary: (Adapted from applicant's abstract): The basal ganglia have been strongly implicated in the control of saccadic eye movements on the basis of clinical and experimental studies. Oculomotor defects occur in patients with extrapyramidal disorders such as Parkinson's and Huntington's disease, and lesions or inactivation of the striatum and other basal ganglia nuclei can produce such defects experimentally.
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The oculomotor zone of the striatum is centered in the caudate nucleus. This nucleus projects to the substantia nigra, pars reticulata (SNr), which in turn projects to the superior colliculus. Evidence suggests that this circuit is a release circuit for saccades. The oculomotor zone has been investigated intensively with conventional single unit recording methods in highly over-trained macaques. The results of these experiments suggest that single units in the oculomotor zone of the caudate nucleus have response properties that resemble those in saccade-related regions of the frontal cortex, including the frontal eye field (FEF), the supplementary eye field (SEF) and the dorsolateral prefrontal cortex (DLPFC). These include responses in visually guided and memoryguided tasks and in sequential saccade tasks. Nothing is yet known, however, about the ensemble activity of saccade-related neurons in the oculomotor zone of the striatum (OMZ-S), or its cortico-basal ganglia loops with the FEF, SEF and DLPFC. Nor is it known how activity is modulated in the oculomotor zone and its associated cortical loops as monkeys acquire procedural learning tasks, behavior thought to be a core function of the basal ganglia. We hypothesize that during learning neurons in the oculomotor zone of the striatum will show progressively more task-related activity and that during the overtraining period population-level coding will emerge in this oculomotor zone. We further hypothesize that temporally coordinated patterns of activity will emerge in cortico-basal ganglia loops during learning and that these will be detectable using chronic multi-unit recording methods. We propose experiments based on preliminary studies to record chronically in 1-2 week bouts from initially naive macaques as they learn procedural saccade tasks. Using multiple tetrodes, stereotrodes and conventional electrodes, we Propose to study multi-unit neural activity in the oculomotor zone of the striatum during acquisition (Aim 1), to study the functional local network architecture of the oculomotor zone during performance (Aim 2), and to study activity in cortico-basal ganglia loops with simultaneous ensemble recordings in the oculomotor zone of the striatum together with the FEF, SEF and DLPFC (Aim 3). The results obtained will have significance for understanding forebrain oculomotor control circuits and for understanding oculomotor defects in extrapyramidal disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF DBS ON POSTURE AND OROMOTOR CONTROL Principal Investigator & Institution: Horak, Fay B.; Senior Scientist and Professor; None; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-MAR-2001; Project End 31-DEC-2005 Summary: (Adapted from the Applicant's Abstract): Balance, gait, speech, and swallowing deficits are major causes of disability in patients with Parkinson's disease (PD). In many patients, these "axial symptoms" are resistant to levodopa therapy. A potential advantage of deep brain stimulation (DBS) of globus pallidus internal (GPi) and the subthalamic nucleus (STN) could be improvement of these axial motor symptoms. Our long-term goal is to determine the effects off DBS on axial motor control in order to understand the role of the basal ganglia in centrally (voluntarily) and peripherally (automatically) initiated axial movements. We hypothesize that there are multiple motor outputs from the basal ganglia with differing sensitivity to dopamine and DBS. The goal of this project is to distinguish functionally different basal ganglia control mechanisms for the axial motor system by their unique patterns of response to DBS and levodopa when used separately and when used in combination. We hypothesize that DBS will he more effective than levodopa and that STN stimulation will be more effective than GPi stimulation for axial parkinsonian symptoms. This project will take advantage of a unique opportunity to rigorously quantify the effects of
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chronic DBS in radiologically-identified human basal ganglia in a randomized, doubleblind study. These studies will quantify forces and movements in two types of postural and oromotor tasks: peripherally triggered, automatic responses to external cues and centrally-initiated voluntary movements. The specific aims are: (1) To determine how DBS affects centrally-initiated and peripherally-triggered postural control. (2) To determine how DBS affects centrally-initiated and peripherally-triggered oromotor control. (3) To investigate the interactions of DBS and levodopa treatment on postural and oromotor control. (4) To determine effects of the site (GPi versus STN) of DBS on postural and oromotor control. These experiments will quantify the efficacy of DBS and levodopa both separately and when combined for balance and oromotor deficits in patients with PD. Quantifying two types of postural and oromotor control in the same subjects will also substantially increase our understanding of the role of the basal ganglia in axial motor control. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL MAGNETIC RESONANCE IMAGING OF THE BRAIN Principal Investigator & Institution: Hyde, James S.; Professor; Biophysics; Medical College of Wisconsin Po Box26509 Milwaukee, Wi 532260509 Timing: Fiscal Year 2002; Project Start 01-JUL-1995; Project End 31-MAR-2003 Summary: The central theme of this Program Project competitive renewal proposal is the fundamental development of functional magnetic resonance imaging (fMRI) into a quantitative basis of mental health. Project I proposes a testable model of fMRI contrast expressed in terms of cerebral blood flow, blood volume and metabolism. It uses a rat fMRI model as well as human subjects to probe issues of fMRI spatial resolution and temporal response and of spontaneous fluctuations in these physiological parameters. Project II addresses polymodal sensory and attentional interactions. It seeks to determine rules governing polymodal interactions using visual and auditory motion processing paradigms as an essential step in understanding sensory and attentional deficits caused by brain pathology. Project II is designed to understand how temporal information is represented in the brain. Using pharmacological probes of normal subjects and studies of patients with basal ganglia disease, this project will test the hypothesis that a unified neural system mediates both perceptual and motor timing. Project IV is built on the experimental observation that "negative" fMRI responses are most frequently seen in brain areas that have also been implicated in semantic processing. It tests the hypothesis that non-semantic tasks produce decreases in neural activity in regions normally engaged in semantic processing. If true, novel research approaches to several neuropsychiatric diseases become available. Core A, Administration, in addition to normal activities, places emphasis on coordinating development of local brain gradient and RF coil technology. Core B focuses on fMRI technology development including interactive real time fMRI at 1/5 and 3 Tesla and extension of the integrated software system AFNI developed in the previous funding period. Core C provides stimulus delivery and subject monitoring capabilities and will continue to refine the Mock scanner for acquiring behavioral and psychophysical data in a simulated MRI environment. These closely integrated initiatives seek to extend fMRI beyond simple mapping into a technique for probing the integration of diverse brain systems in order to make further progress towards the long-term goal of application of fMRI to neuropsychiatric disease and mental health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GABA-MEDIATED ANTICONVULSANT ACTIONS AND BASAL GANGLIA Principal Investigator & Institution: Gale, Karen N.; Associate Professor; Pharmacology; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2002; Project Start 01-MAR-1984; Project End 31-AUG-2005 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENE EXPRESSION IN HIV ASSOCIATED DEMENTIA BRAIN Principal Investigator & Institution: Shapshak, Paul; Research Professor; Psychiatry and Behavioral Scis; University of Miami-Medical Box 248293 Coral Gables, Fl 33124 Timing: Fiscal Year 2002; Project Start 15-JUL-2001; Project End 31-MAR-2005 Summary: (provided by applicant): HIV-1 infection of the brain can result in HIV-1 associated dementia (HAD) and HIV encephalitis (HIVE). HIV-infected cells release viral proteins such as envelope and tat that have direct toxic effects in the brain. Indirect effects include gene expression induced in infected and uninfected cells such as production and release of toxic molecules. The host genes that produce these toxic molecules may be placed in functional groups that include NMDA receptors, chemokines, cytokines, growth factors, their receptors, apoptosis genes, nitric oxide synthases, cell surface markers, adhesion molecules, and toxic glutamic, arachidonic, and quinolinic acid pathways. We will focus on the basal ganglia since this is a region where effects of infection have been demonstrated using brain imaging, clinical, and molecular analyses. AIDS brain tissue diagnosed with and without HAD and HIVE will be provided by the National NeuroAlDS Tissue Consortium. We will micro-dissect individual macrophage-lineage cells, astrocytes, and neurons from tissue sections using LCM to attain specificity. We will use Affymetrix High Density Gene Chip HU 95A Arrays with 12,000 human genes and ESTs to identify changed expression profile of these genes related to HIVE and HAD. Prior techniques such as Northern blots or gel shift assays were more limited in their approach. Affymetrix GeneChip Analysis Suite and GeneCluster will be used for data analysis and we will assess the statistical significance of changes in gene expression observed in each cell type by comparing the results to those obtained from random permutations of the data. We will also confirm gene expression changes using Real Time RT-PCR. In situ hybridization and immunohistochemistry will be used to determine cell specificity of target gene detection to determine the pathological significance of these genes. This exploratory R21 proposal will obtain the preliminary information needed for a larger-scale R0l study to increase the number of cases, refine and increase the number of genes analyzed, and more specifically study those genes whose expression significantly changes as a result of HAD and HIVE. Gene targeting for therapeutic intervention of HAD and HIVE will be feasible. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC ABBERATIONS IN HPRT DEFICIENCY Principal Investigator & Institution: Friedmann, Theodore; Professor; Pediatrics; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Lesch Nyhan disease (LND) is a complex neurobehavioral disease caused by deficiency of the X-linked purine salvage pathway
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enzyme hypoxanthine guanine phosphoribosyl transferase (HPRT). The abnormal neurological phenotype includes retardation, choreoathetosis and self-injurious behavior. The CNS defects are associated with a basal ganglia deficiency of dopamine (DA). A mouse HPRT knockout model displays a relatively normal neurological phenotype but also shows a deficiency of dopamine in the striatum. Primary cultures of midbrain neurons from HPRT-deficient mice demonstrate a reduction of dopamine levels and dopamine uptake. However, to date there has been relatively little progress toward an understanding of the mechanisms by which HPRT deficiency leads to dopamine deficiency. To identify the potential intermediary role of secondary genes functionally downstream of HPRT activity, we have used microarray gene expression analysis on commercially available MU74 oligonucleotide mouse genome chips that interrogate approximately 12,000 known genes and ESTs. In preliminary comparisons of gene expression in dissected striata from wild type and HPRT-deficient mice, we have detected reproducible changes in the expression of a small number of genes and ESTs, including those encoding translation initiation factors IF2s3 and IF3s1, genes associated with striatal dopaminergic neuron function such as sepiapterin reductase that regulates expression of the tetrahydrobiopterin co-factor of tyrosine hydroxylase, and casein kinase I-epsilon that phosphorylates DARPP-32, the principal striatal target for dopamine function. We have also found preliminary evidence for dysregulation of a number of other cDNAs and ESTs of still uncertain relevance to HPRT deficiency. We propose now to complete a more thorough genome characterization of normal and HPRT-deficient mice, to examine the functional effects of aberrant expression of these genes in cultured midbrain and striatal DA neurons and in transgenic and knockout mice. We also plan to determine the biochemical and neurotransmitter effects of genetic correction of these functions by gene transfer techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC REGULATION OF TELENCEPHALON DEVELOPMENT Principal Investigator & Institution: Rubenstein, John L.; Professor; Langley Porter Psychiatric Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): The central tenet of this proposal is that the Dlx family of homeobox genes is essential for regulating the differentiation and function of forebrain GABAergic neurons. Accordingly, I suggest that the Dlx genes are required for controlling the development, and perhaps the function, of intemeurons in the cerebral cortex, and projection neurons in the basal ganglia. Therefore, understanding the functions of the Dlx genes should yield insights into the roles of GABAergic neurons in forebrain neural systems, and may provide insights into disorders of the forebrain due to defects in GABAergic neurons. The experiments described herein use standard and conditional genetic methods to alter the expression of the Dlx genes in developing mice. These methods will allow us to study the effects of deleting individual and/or multiple Dlx genes on the development and function of forebrain GABAergic neurons. In addition, we will investigate the effects of ectopically expressing the Dlx genes. These studies have implications for understanding the genetic pathways that regulate the specification, differentiation and function of forebrain GABAergic neurons, and have implications for understanding the molecular bases of human disorders of GABAergic neurotransmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GLUTAMATE IN PARKINSON'S DISEASE Principal Investigator & Institution: Greenamyre, John T.; Professor; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-JAN-1995; Project End 31-MAY-2004 Summary: (Verbatim from the applicant's abstract) Loss of striatal dopaminergic innervation in Parkinson's disease (PD) is associated with complex changes in the functional and neurochemical anatomy of the basal ganglia. Prominent among the neurotransmitters; altered in PD is the glutamatergic system. For example, the glutamatergic pathways from subthalamic nucleus to the internal segment of globus pallidus and the substantia nigra pars reticulata become overactive after nigrostriatal dopamine depletion. Moreover, there is increasing evidence that corticostriatal projections also become overactive in models of PD. Our laboratory and others have shown that this glutamatergic overactivity has clinically relevant functional consequences and contributes importantly to the pathophysiology of parkinsonian signs and symptoms. Stereotactic or systemic blockade of glutamate receptors has remarkable antiparkinsonian and antidyskinetic effects in experimental animals and in patients with PD. We propose to continue to study in a systematic fashion the effects of various classes of glutamate antagonists in MPTP-treated parkinsonian monkeys, and to examine functional changes in the glutamatergic system in this model of PD. In so doing, we expect to identify viable pharmacological targets for therapeutic intervention in PD. Specifically we propose to: 1. Continue to examine the antiparkinsonian efficacy of a wide range of glutamate antagonists in MPTP-treated parkinsonian monkeys 2. Use various combinations of glutamate antagonists, individually demonstrated in Specific Aim 1 to be efficacious, and test for additive or synergistic actions. 3. Compare the development and severity of dyskinesias in de novo parkinsonian monkeys treated chronically with (1) levodopa alone, or (2) a combination of levodopa and an NMDA antagonist. 4. Examine the antidyskinetic efficacy of NMDA and AMPA receptor antagonists and glutamate release inhibitors in monkeys with established levodopainduced dyskinesias. 5. Use immunocytochemistry and immunoautoradiography to map changes in basal ganglia glutamate receptors in MPTP-treated monkeys, and to use in vivo [3CH]dihydrorotenone binding to map metabolic changes in these brains. By using techniques ranging from measurement of receptor subunit protein levels to preclinical testing of drugs in parkinsonian monkeys, we plan to take a comprehensive approach to the study of glutamate in Parkinson s disease. It is anticipated that our studies will result in an improved understanding of the pathophysiology of this disorder and lead directly to improved therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GP120-MEDIATED CELL DEATH IN THE BASAL GANGLIA Principal Investigator & Institution: Nosheny, Rachel L.; Neuroscience; Georgetown University Washington, Dc 20057 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2006 Summary: (provided by applicant): More than 50% of human immunodeficiency virus type 1 (HIV-1) infected individuals experience neurological and psychiatric problems that are collectively termed the AIDS Dementia Complex (ADC). The current global AIDS crisis highlights the need for therapeutic strategies to treat ADC. A wealth of experimental data has implicated glycoprotein gpl20, an HIV-derived envelope protein that facilitates viral entry into cells, in the cell death associated with ADC. Clinical observations of ADC patients, in vitro characterization of cell types vulnerable to gp 120
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neurotoxicity, and preliminary in vivo data in our laboratory suggest that basal ganglia dysfunction, especially of the nigro-striatal pathway, is integral to the neurological manifestations in ADC. Neurotrophic factors are naturally occurring proteins that are essential for brain development and maintenance of neuronal populations affected in ADC. The proposed experiments will examine the hypothesis that gp 120 causes cell death in the basal ganglia and that neurotrophic factors can protect against gp 120mediated cell death. This neuroprotection in turn may limit neurological complications associated with HIV infection in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HEMISPHERIC SPECIALIZATION AND COMMUNICATION Principal Investigator & Institution: Hopkins, Williams D.; None; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2005 Summary: (provided by applicant): The long-term objectives of the proposed studies are to understand the role that early environment plays in the development of asymmetries in manual gestures and facial expressions and their relationship to different structures of the brain. In the proposed research, behavioral studies on functional asymmetries in hand use for gestural communication and facial expressions used with referential vocalizations will be correlated with neuroanatomical asymmetries as assessed by magnetic resonance imaging (MRI). Specifically, whether hand use for gestures represents a unique functional asymmetry or whether it reflects a general asymmetry for all motor functions will be assessed by comparing handedness indices for gestures compared to motor tasks with similar situational demands. In another series of experiments, the influence on vocal communication on the expression of hand use for referential gestures will be assessed to determine whether the vocal signals enhances or inhibits the magnitude of asymmetries in communicative behavior. In a third set of experiments, asymmetries in facial expressions that made by chimpanzees that have a referential function will be compared to asymmetries in facial expressions that are not accompanied by the use of a referential vocalization. Finally, asymmetries in gestural communication and facial expressions will be correlated with asymmetries in the brain from specific regions of interest including the planum temporale, Brodmann's area 44, the motor/hand area of the precentral gyrus, cingulate gyrus and basal ganglia. Of specific interest in all analyses will be, the comparison of chimpanzee subjects that have been reared by human compared to those reared by chimpanzees. This comparison will allow for determination of how human environments and communication systems alter the development of communicative behavior and the cerebral organization of chimpanzees. Overall, the proposed research will lead to a better understanding of factors which influence the development of laterality in the central nervous systems and behavioral and communicative correlates of these asymmetries. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HEPATIC NEUROCHEMISTRY
ENCEPHALOPATHY--NEUROPSYCHOLOGY
&
Principal Investigator & Institution: Thomas, Michael A.; Associate Professor; Radiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 05-AUG-1999; Project End 31-JUL-2004
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Summary: (Verbatim from the Applicant's Abstract) Hepatic Encephalopathy (HE) is a well-recognized complication of cirrhosis. These patients display a variety of neuropsychological deficits as well as clinical and serum ammonia abnormalities. Subclinical hepatic Encephalopathy (SHE) is a subtler accompaniment of cirrhosis that is associated with neuropsychological abnormalities without significant neurologic findings such as asterixis. Although neuropsychological tests are the current standard for diagnosing SHE, the results are non-specific and reveal little about the underlying neurochemical processes. Cerebral Magnetic Resonance Spectroscopic (MRS) metabolic alterations and MRI signal abnormalities in the basal ganglia reveal a relationship between neuropsychological functioning and biochemical abnormalities found in patients with SHE. This study will involve collaboration among hematologists, radiologists, psychiatrists, MR physicists and neuropsychologists. We will identify a total of 60 liver failure patietns who have SHE and compare them to 60 healthy control subjects. These patients and healthy controls will undergo clinical assessment by hepatologists and neuropsychiatric evaluation by psychiatrists. Subsequently, they will undergo a comprehensive series of neuropsychological tests to characterize the nature of their neurocognitive deficits. Following these tests, all subjects will undergo MR Imaging and Spectroscopic (MRI/MRS) examinations. We aim to use 1H MRS to meare and compare absolute cerebral metabolite levels of myo-inositol, choline, and glutamine/glutamate in the frontal lobe, parietal lobe and basal ganglia of a matched group of SHE patients and healthy controls. The resulting MRS and MRI data will be quantitatively analyzed and correlated with the results of neuropsychological testing and clinical examination. Multivariate methods and correlational analysis will be used to test hypotheses regarding differences between SHE patients and controls. We hypothesize that myo-inositol will be decreased, glutamine/glutamate will be increased and choline will be decreased in patietns with SHE. We propose that these underlying biochemical abnormalities will be correlated with clinical, neuropsychiatric and neuropsychological aspects of SHE. If these relationships are found, they will provide an improved biochemical understanding of the underlined aspects of SHE as characterized y clinical and neuropsychological testing. This enhanced understanding of pathophysiology will improve our ability to diagnose and treat this condition, resulting in improved patient outcomes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INFLUENCE OF THE BASAL GANGLIA ON CEREBELLAR ACTION Principal Investigator & Institution: Gibson, Alan R.; Staff Scientist; St. Joseph's Hospital and Medical Center 350 W Thomas Rd Phoenix, Az 850134409 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): Diseases affecting the basal ganglia produce a variety of movement deficits, and these deficits are often totally disabling. Parkinson's disease, which affects about 1.5 million Americans, is a basal gangliar disease that leads to tremor, decreased spontaneous movement and slowness of voluntary movement. Drug treatment of Parkinson's disease with L-DOPA is only partially effective in relieving the motor symptoms of the disease, and prolonged drug treatment leads to severe side effects such as uncontrollable involuntary movements. Deep brain stimulation at specific sites in the basal ganglia can provide effective relief of Parkinson symptoms. Neither drug treatment nor deep brain stimulation restores damaged neural circuitry in the basal ganglia. Therefore, it is likely that these therapies prevent abnormal basal gangliar output from disrupting processing in other structures related to movement control. One major neural structure related to movement control is the
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cerebellum, but there are no direct connections between the cerebellum and the basal ganglia. We have discovered that disrupting activity in the cat red nucleus, which connects cerebellar output to the spinal cord, can produce motor symptoms that are strikingly similar to those of Parkinson's disease. The general hypothesis underlying this proposal is that motor deficits produced by basal gangliar disease are mediated by pathways that allow basal gangliar output to disturb processing in structures related to the cerebellum. Specifically, we hypothesize that basal gangliar output from the cat entopeduncular nucleus affects activity of cells in zona incerta, which affects activity of cells in the red nucleus. Our experiments will: 1. Identify regions in the related nuclei that contain cells related to forelimb movement. 2. Determine how these forelimb regions affect movement with activation and inactivation by injection of receptor antagonists. 3. Develop an acute and chronic cat model of basal gangliar disease to test critical aspects of the hypothesis. 4. Identify additional brainstem pathways that allow basal gangliar output to influence cerebellar circuits. The results will provide a deeper understanding of how the basal ganglia and cerebellum interact to control limb movements and will lead to new approaches for the treatment of movement disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTEGRATIVE FUNCTIONS OF PRIMATE PREFRONTAL CORTEX Principal Investigator & Institution: Miller, Earl K.; Picower Professor of Neuroscience; Brain and Cognitive Sciences; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 01-JAN-1997; Project End 31-JAN-2007 Summary: "Divide and conquer" seems to dominate many neural analyses: There are specialized systems for analyzing different types of information. Cognition requires synthesizing their results. To plan and execute complex, goal-directed behaviors we must learn "the rules of the game": predictive relationships between disparate sensory events, environmental context, the possible actions and consequences. This depends on brain systems specialized for learning and memory: the prefrontal cortex (PFC), basal ganglia (BG) and hippocampal systems (HS). Damage to any of these systems, or their disconnection, impairs rule learning. Previous studies have shown that neural correlates of acquisition and/or representation of concrete (specific) rules and higher-level abstract rules (general principles) are prevalent in the PFC, a brain region central to rule-based behaviors. But our understanding is limited by our lack of knowledge about the respective contributions of, and PFC interactions with, the other critical systems: the BG and HS. The main goal of this project is to provide that knowledge. We plan to simultaneously study neural activity from up to 28 electrodes implanted these systems while monkeys larn and follow concrete rules )conditional visuomoter associations between an object and a saccade direction) and follow abstract rules (matching and nonmatching rules applied to new stimuli). This will afford a precise assessment of the respective contributions of the PFC, BG, and GS to complex goal-directed behaviors and insight into the underlying neural circuitry. Our specific aims are: 1. To compare and contrast the neural representation of concrete rules in the PFC with anatomically and functionally-related systems (BG and HS). 2. To assess the relative contributions of PFC, BG and HS to rule acquisition by comparing neural correlates of their learning. 3. To compare and contrast the neural representation of abstract rules in the PFC with the BG, and HS. As rule learning is fundamental to all higher-order behavior, data from this project has the potential to impact on our understanding of a wide range of behaviors and human and human disorders. The ability to glean rules and principles from experience is disrupted in a variety of neuropsychiatric disorders such as autism and
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schizophrenia. By identifying brain structures important for these abilities, discerning their relative roles, and uncovering their neural mechanisms, we can open a path to drug therapies designed to alleviate their dysfunction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LEARNING IN THE HUMAN MOTOR CORTEX Principal Investigator & Institution: Ashe, James; Associate Professor; Neuroscience; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2004; Project Start 20-APR-2000; Project End 31-MAR-2008 Summary: (provided by applicant): The long-term objective of this proposal is to understand how the brain learns and control movement sequences. As Lashley recognized more than half a century ago, much of our behavior, from the performance of organized movements to the ability to use language, is based on our capacity to detect, learn, and produce sequences. In the current proposal, we use variants of the serial reaction time (SRT) task and functional imaging in human subjects to examine the neural substrates responsible for learning the fundamental structure of movement sequences, the brain areas responsible for modulating learning through reward and punishment, and the extent to which the brain uses similar strategies for learning temporal and spatial sequences. We will test the following hypotheses. (1) During sequence learning cortical motor areas detect and learn transitions from one element to the next, while the basal ganglia encode the whole structure of sequenced movements. (2) Reward and punishment have direct but differential effects on motor sequence learning and this will be reflected by proportional changes in the activity of the basal ganglia. (3) Learning sequences of temporal intervals will engage a similar set of brain areas to those involved in learning spatial sequences and will not involve the cerebellum. Impairment in the ability to produce sequences is an important component of the disability experienced by patients with Parkinson's disease. The work outlined here will provide a fundamental understanding of these disabilities and may lead to the development of strategies for rehabilitation and treatment of these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISM OF SENSITIZATION TO COCAINE Principal Investigator & Institution: Angulo, Jesus A.; Hunter College Room E1424 New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF ADULT SONG PLASTICITY IN BENGALESE FINCHES Principal Investigator & Institution: Brome, Clinton R.; Physiology; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-OCT-2005 Summary: (provided by applicant): Vocal learning and control in songbirds, a system with many striking parallels to human speech, is used here as a model system to address general issues in the sensorimotor learning and control of complex behaviors. These issues include the production of sequences of stereotyped motor acts, the adaptive correction of errors in a motor plan, and the role of a basal ganglia circuit in adult motor
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control and plasticity. In the first part of this work, altered auditory feedback will be used to probe how this feedback is involved in both the on-line control of song production and in longer-term adaptive corrections to motor output. Specifically, mechanisms involved in the deterioration of song sequence under conditions of disrupted feedback will be investigated, as will the mechanisms involved in the active maintenance of adult song. In the second part, lesions in the "anterior forebrain pathway" (AFP), a basal ganglia-forebrain circuit strongly implicated in juvenile song learning, will be used to investigate the role of this circuit in adult song plasticity and production. These experiments will further our understanding of the avian song system and of the role of sensory feedback in motor learning and control, both generally and with particular relevance to human speech. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: METHAMPHETAMINE NEUROTOXICITY
AND
HIV
PROTEIN-INDUCED
Principal Investigator & Institution: Maragos, William F.; Associate Professor; Neurology; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2002; Project Start 15-FEB-2001; Project End 31-DEC-2005 Summary: Several lines of evidence indicate that the basal ganglia are highly susceptible to infection with the human immunodeficiency virus (HIV). However, the pathogenesis of basal ganglia dysfunction is not well understood. Patients with HIV infection often abuse drugs such as methamphetamine, a drug that is well known to also cause long-term structural and functional changes to the basal ganglia. There is now mounting evidence that "virotoxins" (viral products released from infected cells) and methamphetamine share a common mechanism, which leads to neuronal damage. Two such products are the HIV proteins gp120 and Tat. In this proposal, we will examine the degree of synergy between these virotoxins and methamphetamine by determining the severity of damage they cause to the dopaminergic system in vivo and to human cortical neurons in vitro. To identify common mechanisms that lead to neuronal dysfunction and ultimately, to cell death, we will also examine two pathophysiological processes that contribute independently to virotoxin and MA toxicity, namely reactive oxygen species and the cytokine TNF-alpha. In studying these two processes, we will 2) measure production of compounds of interest (e.g. reactive oxygen species and TNFalpha) and determine the efficacy of a variety of inhibitors on neurotoxicity. To accomplish these goals, we will assess the effects of intrastriatal injections of virotoxins in animals treated with methamphetamine and in vitro in human cortical neurons where cell types can be manipulated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RECEPTORS
METHAMPHETAMINE
TOXICITY
AND
STRIATAL
NMDA
Principal Investigator & Institution: Chapman, David E.; Pharmacology and Toxicology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 01-OCT-2002; Project End 31-JUL-2003 Summary: (provided by applicant) Substituted amphetamines, such as methamphetamine (METH), produce long-lasting, partial loss of central monoamine systems. The postsynaptic consequences of the such loss on basal ganglia function, however, are less well known. Preliminary data from our laboratory suggest that the expression of the NR2A subunit of the NMDA receptor (NMDAR) is increased
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throughout the striaturn 3 weeks following a neurotoxic regimen of METH. The NMDAR is comprised of an NR1 subunit and any of four NR2 subunits (NR2A-D), which confer different properties to the receptor. Whereas the NR2B subunit is expressed at uniform levels throughout striaturn the NR2A subunit, displays greater expression laterally. We have shown that the greater NR2A subunit expression in lateral striatum is associated with NMDAR-mediated excitatory postsynaptic currents (EPSCs) with faster kinetics than those in medial striatum. Others have demonstrated and inability to induce NMDAR-dependent long-term porentiation (LTP) in dorsolateral, but not dorsomedial, striatum. Thus, the level of expression of the NR2A subunit determines NMDAR function in striatum. Thus, this proposal will test the hypothesis that increases in NR2A subunit expression induced by a neurotoxic regimen of METH will alter NMDAR function. This will be accomplished by completing the following specific aims: A) Determine the functional impact of METH-induced changes in NR2A subunit expression on NMDAR-mediated EPSCs in dorsolateral and ventromedial striatum. B) Examine the functional consequences of METH-induced changes in the monoamines and NR2A subunit expression on striatal LTP. The results of these studies will further elucidate postsynaptic changes associated with METH neurotoxicity, and will provide molecular insight into the behavioral and cognitive alterations which ensue a neurotoxic insult induced by METH. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR BASIS OF SYNDROMIC RETINITIS PIGMENTOSA Principal Investigator & Institution: Hayflick, Susan J.; Associate Professor; Molecular and Medical Genetics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: The goal of this project is to isolate and characterize the gene for a form of syndromic retinitis pigmentosa (RP), called Hallervorden-Spatz syndrome (HSS) and characterized by abnormal electroretinogram, lipofuscin accumulation in the retinal pigment epithelium, and early, rapidly progressive pigmentary retinopathy. This autosomal recessive disorder of childhood includes extrapyramidal dysfunction with iron accumulation in the basal ganglia. Though lipid peroxidation is an hypothesized mechanism leading to the HSS phenotype, no knowledge exists of the molecular or biochemical defect. We propose a molecular genetic approach to understanding this syndromic form of RP. Our specific aims are to 1) identify the gene for HSS, designated NBIA1 (Neurodegeneration with Brain Iron Accumulation, type 1) by completing the physical map of the critical region, identifying and screening candidate genes, and demonstrating deleterious mutations; 2) develop the molecular diagnosis of HSS using mutation studies and genotype-phenotype correlation; 3) characterize the HSS gene and its protein product at the tissue, cellular, subcellular and molecular levels using homology to model organisms, sequence analysis, histopathology, immunohistochemistry and studies of tissue expression patterns; and 4) isolate the murine homolog of the HSS gene and develop a mouse model for HSS in order to study its pathophysiology. Knowledge about the HSS gene will allow molecular diagnosis in individuals suspected to have this disease. As well, prenatal diagnosis of this fatal condition will be feasible. By delineating the pathophysiologic process in HSS, we may begin to develop rational therapies, which may be of benefit in treating other forms of RP, as well. Rare diseases often illuminate the mechanisms at work in common, related disorders. An advantage to studying syndromic RP is that the pleiotropic manifestations provide a context to help delineate the mechanism of retinopathy. The HSS gene is not retina-specific, and a defect in it must account for rod photoreceptor degeneration as
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well as regional brain iron accumulation. Furthermore, since defects in this non-retinaspecific process may cause other forms of syndromic and isolated RP and may be integral in disorders of lipofuscin accumulation, including aging macular degeneration, identification of the HSS gene may lead to greater understanding of RP as well as the macular dystrophies associated with senescence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR ETIOLOGY OF EARLY ONSET TORSION DYSTONIA Principal Investigator & Institution: Breakefield, Xandra O.; Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 15-JAN-1999; Project End 31-DEC-2002 Summary: Torsion dystonia is one of the most common and least well understood of movement disorders in humans. Affected individuals manifest contracted, twisting postures due to abnormal neurotransmission of the basal ganglia. This Program is directed towards elucidation of neuronal dysfunction in the early onset form of dystonia, which commences in childhood and can be completely disabling. The DYTl gene responsible for this condition is inherited in an autosomal dominant manner with low penetrance and has been recently cloned by our group. Most cases of this disease are caused by loss of a glutamic acid residue in the carboxy terminus of a novel ATPbinding protein termed torsinA. This gene is expressed selectively and at high levels in dopaminergic neurons in the substantia nigra. TorsinA defines a new gene family with distant relationship to the heat shock/Clp proteins. Our hypothesis is that defects in this protein underlie susceptibility which can lead to diminished release of dopamine into the striatum and, in turn, to altered modeling of neuronal circuitry in the basal ganglia during childhood development. The resulting imbalance in neurotransmission would then affect processing of motor information in this critical region of the brain. Studies are designed to elucidate the role of members of the torsin gene family in this and other forms of dystonia, and to identify other genes which may affect penetrance by linkage and mutational analysis. Brain tissue from human controls and affected individuals, as well as transgenic knock-in mice, will be examined by immunocytochemistry and in situ hybridization to elucidate changes in the distribution and density of proteins involved in neurotransmission, including D1 and D2 receptors. The transgenic mice will also be evaluated for alterations in the development of neuronal connections in the basal ganglia, in behavior and in response to stress. The intracellular distribution of torsinA and the functional effects of the mutant protein will be assessed in cultured dopaminergic neurons and model neural system using immunocytochemistry and a helper virus-free amplicon vector delivery of normal and mutant genes. Cells will be evaluated for functions related to other members of the heat shock/Clp family, including response to heat shock, uptake and release of dopamine, and mitochondrial function. These studies capitalize on the recent identification of the DYTl gene to understand the molecular etiology of early onset torsion dystonia, to elucidate developmental and stress- related plasticity in the basal ganglia, and to provide insights into therapeutic intervention. Given the apparent involvement of dopaminergic neurons in dystonia and Parkinson's disease, these studies should also provide insight into the latter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOTOR ACTIONS OF CANNABINOIDS IN A PARKINSONS MODEL Principal Investigator & Institution: Sanudo-Pena, Clara M.; Psychology; Brown University Box 1929 Providence, Ri 02912 Timing: Fiscal Year 2002; Project Start 01-JAN-2000; Project End 31-MAR-2002 Summary: The hallmark of Parkinson s disease is a dopamine deficiency in the basal ganglia due to degeneration of dopaminergic neurons in the substantia nigra pars compacta. Because of this, the physiology of the neurotransmitter dopamine in the basal ganglia has been extensively studied. However, none of the current models of basal ganglia function includes the novel cannabinergic neurotransmitter system. The recent cloning and mapping of a nervous cannabinoid receptor unveiled high levels of cannabinoid receptors in the basal ganglia where they are as abundant as the receptors for dopamine. Furthermore, cannabinoid receptor levels in the output nuclei of the basal ganglia, the globus pallidus and the substantia nigra pars reticulata, are the highest in the brain. In recent studies we have described a major modulatory role of cannabinoids in the basal ganglia where they act on both major excitatory (subthalamic) and major inhibitory (striatal) inputs to basal ganglia output nuclei. Cannabinoids block the activation of either input, and the effect observed would be to return the system to basal levels of activity. A complex interaction between the cannabinoid and the dopaminergie system was also observed, blocking each others effects in intact animals and synergizing in the 6-OHDA model. The major modulatory action of cannabinoids in the basal ganglia counteracting both the major source of excitation and the major source of inhibition depending on their level of activity is relevant to Parkinson s disease where the subthalamic nucleus becomes hyperactive. This proposal aims to determine wether cannabinoids could be used alone or in conjunctive therapy with ineffective levels or low doses of dopaminergic drugs to counteract the motor impairments induced by degeneration of the dopaminergic innervation of the basal ganglia. Behavioral, biochemical, and physiological studies will be conducted in parallel to test this possibility. It will also help integrate the cannabinergic system with the current knowledge of basal ganglia physiology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOTOR LEARNING IN PARKINSON'S DISEASE Principal Investigator & Institution: Ghilardi, Maria-Felice M.; Ctr for Neurobiology Behavior; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 30-SEP-1997; Project End 31-JAN-2003 Summary: (provided by applicant): The specific aims of the original proposal were: 1. To determine the effect of Parkinson's disease (PD) on the learning of spatial and temporal features of motor learning tasks, compared to a normally aging population. 2. To test the hypothesis that the deficits in motor learning in PD result from the altered function of specific cortical and subcortical networks whose expression correlates with task performance in age-matched controls. 3. To assess the effect on motor learning of new therapies, such as pallidal ablation and pallidal stimulation. Over the past two and a half year, we have made extensive progress in accomplishing these aims, as described in Progress Report and in the publication track record. In this competing continuation application, we plan to complete the initial research and educational aims and to extend our work. Specifically, we will pursue the following aims: 1. To study the effects of DBS and levodopa administration on motor learning in PD. We have shown that aspects of motor learning are defective in the earliest stages of PD and are associated with
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abnormal brain organization. Preliminary data indicate that these abnormalities are not rectified by levodopa, but, GPi DBS can improve sequence learning and increase activity in brain regions normally involved in this process. Here we ask if STN DBS (which drives GPi and other structures mediating simple and complex motor behavior) can improve performance in PD by modulating the brain circuits involved in sequence learning, similarly to GPi DBS. PET recordings during motor tasks will be conducted in a group of PD patients with STN DBS, a group with GPi DBS, and a group treated with levodopa infusion in on and off conditions. Brain network expression and performance will be compared across groups and conditions. 2. To characterize the progression of motor and cognitive dysfunction in PD. We found that PD patients in stage I and 11 require longer time and need to recruit more brain areas to learn a motor sequence. Here we ask how performance and brain network activation change in relation to disease progression. In this longitudinal study, we will also evaluate changes in acquisition of motor skills other than sequence learning, such as adaptation to new reference frames or novel inertial configuration. We will use tasks we have recently developed and tested in a population of young normal subjects. We will ask the following questions: Which are the normal brain networks involved in the different types of learning? Are they independent or share some common bases? Does their expression change in PD patients in early stages? Does brain network expression in PD change with disease progression? These studies psychophysical and imaging studies will be conducted in the group of PD patients and age-matched controls we have tested in the previous grant period. 3. To study motor learning and execution in hyperkinetic basal ganglia disorders. Studies with "F-fluoro-deoxyglucose (FDG) and PET have demonstrated an abnormal metabolic network in clinically non-manifesting carriers of Idiopathic Torsion Dystonia (ITD) DYT I gene. In preliminary studies, we have found that motor sequence learning may be impaired in these same gene carriers. We plan to complete the psychophysical studies in non-manifesting DYTI carriers and to assess the effect of GPiDBS on rcbf in affected DYTI patients. Specifically, we will ask the following questions: Will non-manifesting DYTI carriers show motor learning and network activation abnormalities that parallel their resting metabolic abnormalities? Will non-manifesting DYT I carriers and dystonic patients show differences in motor learning and network activation? By comparing rcbf before and during pallidal stimulation, we will determine how altering pallidal function affects the expression of activation patterns subserving motor learning in ITD. Overall, these studies will provide the bases for a comprehensive understanding of basal ganglia and related cicuitry in motor learning and execution, as well as for the development of new therapeutical strategies for basal ganglia disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MRSI OF FRONTOSUBCORTICAL CIRCUITS IN BIPOLAR DISORDER Principal Investigator & Institution: Deicken, Raymond F.; Associate Professor; Northern California Institute Res & Educ 4150 Clement Street (151-Nc) San Francisco, Ca 941211545 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (provided by applicant) Developing evidence strongly suggests that bipolar disorder involves localized abnormalities in specific brain structures that participate in fronto-limbic-subcortical circuits regulating mood. The specific structures include the prefrontal cortex, anterior cingulate cortex, thalamus, basal ganglia, amygdala hippocampus, and cerebellum. There is clearly a need for systematic study of these structures in bipolar disorder to determine the magnitude and extent of regional
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neuropathology, which may be too subtle to reliably detect by present quantitative MRI measurements of tissue volume alterations. Subtle neuronal loss or damage has been shown to be readily detectable by proton magnetic resonance spectroscopy (1 H MRS I) measures of N-acetylaspartate (NAA), a neuronal and axonal marker and a reliable indicator of neuronal integrity. Therefore, this proposal will utilize high resolution MRI together with 'H MRSI to determine if there is reduced NAA, with or without tissue volume loss, in the dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, caudate, putamen, hippocampus, and cerebellar vermis in bipolar disorder. MRI derived tissue volumes will be utilized together with NAA and choline measures to make preliminary inferences about regional neuropathologic changes such as neuronal dysfunction, neuronal loss (with or without gliosis), developmental hypoplasia, and synaptic/dendritic pruning failure. Second, this proposal will examine NAA measures in normal appearing white matter (NAWM) and white matter signal hyperintensities (WMSH) of the prefrontal white, subcortical, and periventricular white matter regions. White matter NAA reductions will be interpreted as evidence for axonal loss or dysfunction and evidence for compromised integrity of white matter pathways. Third, this proposal will determine if there is increased NAA. with or without increased tissue volumes, in the thalamus and amygdala in bipolar disorder. Increased NAA and/or increased tissue volumes will be interpreted as evidence for possible increased neuronal number or interneuronal neuropil. Fourth, this proposal will determine if the magnitude and/or extent of regionally specific NAA alterations is different in bipolar I compared to bipolar II disorder. Finally, this proposal will determine if longer illness duration and greater illness severity (defined as a greater number of lifetime hospitalizations for mania or depression) result in more severe brain pathology as measured by the magnitude of regionally specific NAA alterations. Determining whether the neuropathology in different brain regions is a result of progressive damage to the brain over time will have important implications for treatment interventions in binpolar disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL BASIS OF DEPRESSION VULNERABILITY Principal Investigator & Institution: Shumake, Jason D.; Zoology; University of Texas Austin 101 E. 27Th/Po Box 7726 Austin, Tx 78712 Timing: Fiscal Year 2002; Project Start 01-JAN-2003; Project End 31-DEC-2004 Summary: (provided by applicant): The proposed studies will investigate the neural substrates mediating susceptibility to depression in a genetic rat model. Our recent work with the congenitally helpless rat has revealed a pattern of metabolic abnormality in prefrontal cortex (PFC) and anterior cingulate cortex (ACg) that strongly parallels PET and fMRI findings from depressed humans. These rats also appear to have another, much larger, abnormality localized to the paraventricular hypothalamic nucleus (PVH). Based on these results, we seek to further investigate the role of brain regions related to the hypothalamic-pituitary-adrenal axis in congenitally helpless rats. Four specific aims are proposed: 1) Extend metabolic mapping of the congenitally helpless rat brain to regions that provide regulatory input to the PVH (hippocampus, septal area, bed nucleus of the stria terminalis), regions related to monoaminergic function (ventral tegmental area, raphe nuclei, habenula), and other regions implicated in emotional behavior (amygdala, basal ganglia, periacqueductal gray). 2) Test the hypothesis that the PVH metabolic abnormality is related to increased production of corticotropinreleasing hormone (CRH) by performing in situ hybridization for CRH mRNA. 3) Test the hypothesis that elevated CRH secretion will cause metabolic abnormalities in PFC,
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ACg, and other regions similar to those identified in the congenitally helpless rat by chronically administering CRH to normal rats, followed by metabolic brain mapping. 4) Identify brain regions linked to depression remission by administering an antidepressant (fluoxetine) to congenitally helpless rats and determining its effect on regional brain metabolism, CRH mRNA, and behavioral outcome measures. The collective results should help to integrate the roles of the hypothalamus, frontal cortex, and serotonin system in depression and its treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL BASIS OF VOCAL LEARNING Principal Investigator & Institution: Doupe, Allison J.; Professor; Laboratory Medicine; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 01-JAN-2001; Project End 31-DEC-2005 Summary: The long-term goal of this research is to understand the neural basis of learning and memory, especially how the brain learns complex motor behaviors, guided by sensory information. Vocal learning in songbirds provides a useful model system for this purpose, with special relevance to human speech learning. Songbirds learn to produce a copy of a previously memorized tutor song during a period of "sensorimotoi" learning, in which they use auditory feedback of their own voice to refine their vocal output until it matches the memorized song. The work proposed here focusses on a particular part of the system of brain areas devoted to song learning and production, a specialized cortical-basal ganglia circuit known as the anterior forebrain pathway (AFP), because it plays a crucial but illunderstood role both in song learning and in adult vocal plasticity. Moreover, cortical-basal ganglia circuits, which are well conserved evolutionarily, are thought to function in motor and reinforcement learning in many vertebrates, and to be one critical site of dysfunction in a number of neuropsychiatric disorders. Because the songbird AFP is a discrete cortical-basal ganglia circuit controlling a specific behavior, it may prove a particularly tractable system for elucidating the very general functions of such pathways. both normally and in disease. The AFP develops song-selective auditory responses that could participate in the auditory evaluation of song during learning, and shows motor-related activity during singing, but how these sensory and motor responses relate to each other is not clear. Activity in this circuit is also extremely variable from trial to trial, raising the question of how it could reliably encode information or guide song. With simultaneous recordings from multiple neurons in the output nucleus of the AFP, LMAN, during both singing and song playback, the first aim will test the hypothesis that the AFP encodes relevant song- and singing-related information in the form of a distributed, "population" code. A further hypothesis is that specific patterns of AFP neural activity are critical for normal song development, perhaps guiding the formation of connections in the vocal motor nucleus RA. This will be tested with simultaneous recordings of neurons in both LMAN and RA, so that the covariance of their activity and how it relates to vocal output can be analyzed. LMAN-RA interactions will be studied first in normal birds at different stages of learning, and then after experimental disruptions of the pattern of activity in the AFP, in ways that will shed light both on normal synaptic processing within this circuit as well as on how it influences the song motor pathway. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL CONTROL OF TRAINED MOVEMENT Principal Investigator & Institution: Thach, W Thomas.; Professor of Neurobiology & Neurology; Anatomy and Neurobiology; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2003; Project Start 01-SEP-1977; Project End 31-MAY-2008 Summary: (provided by applicant): MAJOR GOALS are to study the roles of the cerebellum and basal ganglia in adapting, learning and storing adjustments of eye-hand coordination. Gaze will be perturbed with laterally displacing prisms (project #1) and with shift of the visual target (project #2 ) to see how monkeys adjust their reaching to visual targets. Two types of adjustment are distinguished, leaming and adaptation. In leaning, a monkey stores two gaze-reach calibrations, and can call each up immediately if it knows each condition. In adaptation, there is only one stored gaze-reach calibration, which must be adjusted back and forth by practice. Project # 1 examines whether the cerebellum and basal ganglia are both necessary for storing learned gaze-reach calibrations. Monkeys will have two gaze-reach calibrations: 1) reaching to and touching a visual target without prisms, in which eyes and reach are aligned, and 2) learned reaching to and touching a visual target with prisms, in which eyes and reach are divergent. Neurons in cerebellar cortex, deep nuclei, and globus pallidus pars interna will be recorded from then inactivated to see if the learned gaze-reach adjustment is abolished. Project # 2 asks how the cerebellar cortex, inferior olive, and parvocellular red nucleus are involved in adapting and learning to touch a visual target that has shifted in mid-reach. At the start of each block of adaptation shift trials, the visual target will shift mid-reach in a novel direction, and continue each trial to shift in that direction for the rest of the block. The monkey must adapt in order to touch the target at its shifted novel location. Then the monkey will have a block of no-shift trials, and must then dis-adapt in order to hit the target where it initially appears. During learning shift trials, the target will shift in a direction that is fixed and therefore predictable throughout the block and all such blocks of trials. The monkey will be informed that this is the learned shift condition and thus can learn it, in addition to the no-shift condition. This project focuses on the problem of how subjects adapt and learn when knowledge of results is delayed after the movement. Recording Purkinje cell firing and recording from and inactivating neurons of the parvocellular red nucleus will help to understand their involvement. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEURAL MODELING AND IMAGING OF SPEECH Principal Investigator & Institution: Guenther, Frank H.; Associate Professor; Cognitive and Neural Systems; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-FEB-1996; Project End 31-JAN-2006 Summary: The primary goal of this research project is the continued development, testing, and refinement of a comprehensive computational modeling framework addressing the neural processes underlying speech perception and production. This framework is defined using adaptive neural networks, allowing comparisons with data from imaging studies of brain function. The proposed research includes five modeling studies and nine closely related functional magnetic resonance imaging (fMRI) experiments to test model predictions. These studies constitute five subprojects to flesh out different aspects of the investigators' modeling framework. The first subproject, modeling and imaging studies of neural map formation in the auditory cortical areas,
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will extend their earlier studies into the nature of sound categories in the auditory system (e.g., phonemic categories) and the warping of auditory perceptual space evident from phenomena such as categorical perception and the perceptual magnet effect. The second subproject, modeling and imaging studies of visual influences on speech perception, will extend the investigators' earlier work studying the nature of visual influences on speech perception as evidenced by the McGurk effect, and will address learning processes hypothesized to underlie visual-auditory associations. The third subproject, modeling and imaging studies of central aspects of the DIVA model, will address the neural processes underlying the control of speech articulations, including the involvement of the cerebellum in normal subjects and subjects with cerebellar damage, and the effects of auditory and somatosensory feedback perturbations to activations in different brain areas. The fourth subproject, modeling and imaging studies of movement selection, initiation, and sequencing, will address the involvement of the supplementary motor area, anterior cingulate area, and basal ganglia in speech production. In the fifth subproject, a distributed model of cortical and subcortical interactions in speech, the results of earlier projects will be combined into a comprehensive model of the neural processes underlying speech perception and production. The modeling hypotheses have been specifically designed to be testable with existing or easily attainable fMRI techniques. Several new imaging and data analysis techniques will also be investigated to stay abreast of the most effective methods for testing the hypotheses. When appropriate, these techniques will be utilized to improve the experiments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPATHOLOGY SCHIZOPHRENIA
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Principal Investigator & Institution: Roberts, Rosalinda C.; Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, Md 21201 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Schizophrenia is a devastating illness, with unknown pathophysiology, that affects 1% of the world's population. The experiments in the following revised proposal will focus on the basal ganglia and dopamine (DA) pathology in schizophrenia (SA1) and relate these changes to those occurring in rats treated with antipsychotic drugs (APDs) (SA2). Our preliminary data shows abnormalities in morphology of DAergic neurons in the substantia nigra (SN) and in the number of TH+ striatal synapses in electron microscopic (EM) studies of postmortem tissue from subjects with schizophrenia (SZ), similar structural changes and a decrease in number of TH+ cells in rats treated with APD. SA1 tests the hypothesis that the DA system is perturbed in the basal ganglia of SZ, using tissue from normal controls, SZ treated with typical or atypical APDs or off-drug. SA2 tests the hypothesis that anatomical changes observed in SN and ventral tegmental area (VTA) of SZ are the results, in part, of APDs, and will determine the contributing physiological mechanisms. In both aims, we will determine if the morphological alterations seen will show regional variations that are consistent with the differential effects of typical and atypical APDs on the activity of midbrain DA neurons. In this revision, we have modified the EM analysis of the SN and added 3 parallel experiments in both the human tissue and rats (treated with haloperidol or clozapine or controls). In SA1a the synaptic organization of DA labeled profiles will be analyzed in the human striatum at the EM level. In SA1b & SA2a, the number and size of Nissl stained, and TH+ cells double labeled with the DA transporter (DAT), or a selective marker of DA cells, SK3, will be determined using
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stereological methods in the SN/VTA. In SA1c & SA2b at the EM level, the integrity of subcellular organelles and the synaptic organization to the TH+ neurons (also labeled with DAT or SK3) will be studied. Using in situ hybridization SA1d & SA2e will determine if TH synthesis is affected at the level of transcription. SA1c & SA2d will determine if cytoskeletal proteins are upregulated. SA1f & SA2e will determine if the loss of TH in neurons is due to changes at the translational level by using Western blot analysis. SA2f will study the time course of the anatomical changes observed during APD treatment and relate these changes to the development of depolarization (DP) block. SA2g tests the hypothesis that morphological alterations in SN/VTA neurons will not occur in rats treated with APD if DP block is prevented (with a unilateral striatal lesion). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPHARMACOLOGY OF DRUGS OF ABUSE--AMPHETAMINE Principal Investigator & Institution: Rebec, George V.; Chancellors' Professor of Psychology And; Psychology; Indiana University Bloomington P.O. Box 1847 Bloomington, in 47402 Timing: Fiscal Year 2002; Project Start 01-AUG-1986; Project End 31-DEC-2003 Summary: (Adapted From The Applicant's Abstract) Amphetamine and related drugs of abuse elicit species-specific motor responses characterized by repetitive or stereotyped patterns. Research on animals, typically rodents, as models of the human response, has implicated the striatum and related basal ganglia circuitry in the motor-activating effects of these drugs. Critical elements of this circuitry include both dopamine- and glutamate-containing fibers that contact neurons in dorsal striatum. During amphetamine-induced motor activation, these neurons establish a pattern of discharge activity mediated, at least in part, by a complex interaction between dopamine and glutamate inputs. Research in this application extends this line of work on behaving animals in two directions. One involves characterization of the neuronal response pattern to amphetamine in substantia nigra pars reticulata, a major target of striatal neurons and an important output nucleus of the basal ganglia. After basic neurobehavioral correlations are established, further studies will examine the extent to which amphetamine-induced changes in reticulata neurons are mediated by the striatum via descending GABA-containing projections. The aim is to determine how amphetamine-induced neuronal response patterns established in striatum are represented in reticulata neurons. A second focus of the proposed research is to examine at the single-neuron level how the major transmitters altered by amphetamine-dopamine and glutamate--interact with each other and with GABA to influence the activity of striatal neurons in an intact, normally functioning animal. Dopamine, glutamate, and GABA will be applied directly by iontophoresis to electrophysiologically isolated single units in awake, unrestrained rats. Attention will center on the mechanisms by which synaptic dopamine modulates glutamate- and GABA- mediated responses. A major component of this work also involved iontophoresis of amphetamine and other indirect dopamine agonists in striatum to determine how local changes in dopamine transmission modulate striatal activity and to reveal the synaptic action of these drugs unaccompanied by concomitant activation of other neuronal pathways. Collectively, these lines of research will provide important new information on the neurochemical systems and processes by which amphetamine alters neuronal function and motor behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROPHYSIOLOGY OF BASAL GANGLIA SYSTEM Principal Investigator & Institution: Grace, Anthony A.; Professor; Neuroscience; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-1993; Project End 31-MAR-2003 Summary: (adapted from candidate's abstract): This is a competitive renewal of an RSDA that proposes to use in vivo and in vitro electrophysiological recordings to examine the functional interactions among cortical afferents and the DA system within the NAC of rats. Studies into the etiology of schizophrenia have recently focused on a cortical locus of pathology with emphasis on the prefrontal cortex and the hippocampus. Moreover, owing to the genetic linkage schizophrenia, the impact of developmental disruption has gained prominence in this field. As an extension of our studies demonstrating a gating role for hippocampal input into the NAC, we propose to evaluate the functional interaction NAC afferents and how it may selectively altered by neonatal disruption according to the following specific aims: (1) To characterize the physiology and pharmacology of the responses evoked in NAC neurons in vitro by stimulation of prefrontal cortical, hippocampal, and amygdalar afferents. (2) To examine the pharmacology of DA actions on each of these afferent systems in vitro. (3) to characterize the response properties and types of interaction between pairs of afferents to NAC neurons recorded in vivo. (4) To examine how the DA system affects the afferent-evoked responses and their interactions in vivo, and how these interactions may be altered by psychotropic drugs. This comprehensive characterization of afferent interactions will provide the necessary baseline data for the last specific aim: 5) To compare the effects of developmental disruption in neonates on the interaction between excitatory afferents to the NAC neurons and their regulation by DA in adults. In this way we will gain a better understanding of the nature of these cortical interactions within the NAC, how these systems are modulated by DA, and how they may undergo a compensatory reorganization as a consequence of neonatal damage. In addition to the research plan, an outline for scientific growth over the next five years is presented. This consists of: (1)expanding my participation in basic and clinical research and training; (2) increasing involvement in scientific organizations; (3) taking a leadership role in organizing program project-based research; and (4) expanding the breadth and depth of my laboratory research. This latter goal will be achieved through combination of collaborative ventures using ultrastructural and viral tract tracing techniques, as well as implementing new technologies into my laboratory, including developmental studies and visual patch recordings. Each technique is advanced to address specific research questions rather than simply expanding my technical base. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROPHYSIOLOGY OF WORKING MEMORY IN BIPOLAR DISORDER Principal Investigator & Institution: Adler, Caleb M.; Psychiatry; University of Cincinnati 2624 Clifton Ave Cincinnati, Oh 45221 Timing: Fiscal Year 2003; Project Start 01-JAN-2003; Project End 31-DEC-2007 Summary: (provided by applicant): This NIMH Mentored Patient-Oriented Career Development (K23) Award application is to support Dr. Caleb M. Adler's developing expertise in neuroimaging and bipolar disorder. Bipolar disorder is a common psychiatric illness accompanied by severe morbidity and mortality. Traditionally viewed as a cyclic illness with a return to baseline function between affective episodes, evidence suggests that bipolar disorder is associated with significant deficits in specific
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cognitive domains, particularly working memory. Neuroimaging studies in bipolar patients suggest dysfunction of structures associated with the "network" of brain regions involved in working memory. Consistent with these observations, working memory deficits are observed in bipolar patients across the affective spectrum, suggesting that these deficits represent a "core symptom" of bipolar disorder, rising out of the neurophysiology of the illness. The specific research supported by this award will involve studying neuronal activity associated with working memory inpatients with bipolar disorder and healthy volunteers. The candidate will use fMRI to study patterns of activation in bipolar patients and healthy volunteers while they are performing a series of working memory tasks increasing parametrically in difficulty. Both medicated and unmedicated bipolar patients will be enrolled. In addition to increasing understanding of the neurophysiology underlying working memory deficits in bipolar patients, the candidate seeks to improve our understanding of the effects of medication on activation patterns. A better understanding of this "core symptom" may help clarify the underlying neurophysiologic substrates of bipolar disorder, ultimately suggesting future treatment directions. As a follow-up protocol, the candidate will compare working memory-induced activation in bipolar patients during acute mood states with the previously obtained euthymic data. Working memory deficits are exacerbated in depression and mania; these comparisons may clarify changes in the neurophysiology of bipolar disorder during acute affective episodes. During the course of this K23 award, the candidate will obtain additional training in bipolar psychopathology, functional imaging techniques, cognitive testing and statistical analysis, as well as research ethics. The candidate will integrate these skills with previous training and experience in other areas of functional imaging and clinical psychiatry in order to develop expertise in the investigation of the neurophysiology of bipolar disorder. At the conclusion of this award, the candidate will be well positioned to function as an independent investigator extending this work using other cognitive paradigms and to further examine staterelated cognitive deficits in bipolar disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NIGROSTRIATAL DOPAMINE FUNCTION Principal Investigator & Institution: Tepper, James M.; Professor; None; Rutgers the State Univ of Nj Newark Blumenthal Hall, Suite 206 Newark, Nj 07102 Timing: Fiscal Year 2003; Project Start 01-FEB-1997; Project End 31-MAR-2008 Summary: (provided by applicant): The basal ganglia, and especially the dopaminergic components of this system, are well known to play a central role in the role in the etiology and pathophysiology of several neurological and psychiatric disorders including Parkinson's disease and schizophrenia. More recently, however, mesotelencephalic dopaminergic systems have also been viewed as integral to certain types of learning and memory, affective responses and perception, and several types of higher cognitive function. In vivo, dopaminergic neurons fire spontaneously at low rates. This activity exists along a continuum of firing pattern from a regular pacemakerlike pattern on one end, to an irregular or random pattern to a slow bursty pattern on the other end. Dopaminergic neurons in vivo typically respond to behaviorally relevant environmental stimuli with an increase in firing rate in the form of a low frequency burst that usually lasts for a few hundred milliseconds. The timing of the dopaminergic signal is crucial for many of the functions ascribed to the dopaminergic system in signaling stimulus characteristics, reward salience or predictive error. Although it is clear that switches to the different patterns of activity are triggered by afferent activity, the afferents responsible and in particular the mechanisms of the burst or burst initiation
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are not clear. It is the overall goal of this competing renewal to extend observations made in the last Brant cycle by concentrating on GABAergic mechanisms in the afferent control of substantia nigra dopaminergic neurons studied by in vivo and in vitro neurophysiology, light and electron microscopy and in vivo microdialysis. There are 5 specific aims that will test the following hypotheses: (1) GABA-A receptors on dopaminergic neurons re predominantly or exclusively activated by GABAergic inputs in vivo under typical experimental conditions and activation of GABA-B receptors only occurs when the GABA transporter is saturated by excessive or high frequency Input and/or pharmacological blockade, (2) Most postsynaptic GABA-B receptors on substantia nigra dopaminergic neurons are located perisynaptically, (3) Afferent induced alterations in the pattern of activity of DAergic neurons lead to significant changes in extracellular levels of DA in striatum and substantia nigra, (4) Nigral GABAergic interneurons ore a source of afferent input to DAergic neurons, and (5) The difference in sensitivity to GABA-A receptor agonists between DAergic and GABAergic neurons in substantia nigra is due to a differential GABA-A subunit composition and/or a difference in the density of GABA-A receptors. These data should provide answers to several important questions about the afferent control of nigral dopaminergic neurons which are essential for understanding the normal function of the basal ganglia and which may also point the way toward improved pharmacotherapies for disorders involving the dopamine system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NITRIC OXIDE CONTROL OF CGRP IN TRIGEMINAL NEURONS Principal Investigator & Institution: Durham, Paul L.; Biology; Southwest Missouri State University 901 S National St Springfield, Mo 65802 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The objective of the proposed research is to understand the mechanisms by which nitric oxide (NO) regulates calcitonin generelated peptide (CGRP) gene expression in trigeminal neurons. Serum levels of CGRP are elevated in alt forms of vascular headaches, including migraine. The neuropeptide CGRP is known to play a critical role in the underlying pathology of migraine due to its ability to regulate cerebral blood flow, mediate neurogenic inflammation, and relay nociceptive information to the CNS. Another agent implicated in migraine pathology is nitric oxide (NO). Glyceryl trinitrate, an exogenous NO donor, triggers migraine attacks, while blockade of NO synthesis aborts acute migraine attacks. The cerebrovascular affect of NO is thought to be mediated by the local release of neuropeptides from trigeminal neurons. In this proposal, I will test the hypothesis that NO directly stimulates CGRP gene expression and determine whether serotonergic anti-migraine drugs can repress the effect of NO. Studies proposed in the first specific aim will determine the effect of NO alone or in combination with other inflammatory mediators on CGRP release from trigeminal neurons and whether the anti-migraine drug sumatriptan can repress this effect. The second aim will focus on identifying the basal and NO-responsive regulatory sites in the CGRP promoter. Primary trigeminal ganglia cultures will be transiently transfected with CGRP-luciferase reporter DNA and reporter activity measured. The effect of sumatriptan on basal and NO-stimulated CGRP promoter activity will be determined. The third aim will elucidate the pathways involved in NO signaling in trigeminal neurons. Initially, specific cyclase and kinase inhibitors and activators will be used to identify the major pathway(s) involved in regulating the synthesis and release of CGRP. Further studies of individual pathways will utilize phosphospecific antibodies and signaling pathway detection kits. The effect
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of sumatriptan on NO-activated pathways will be determined. The overall goal of these studies is to gain insight into basal and NO regulation of CGRP gene expression in trigeminal neurons that may lead to the development of novel therapeutic strategies for migraine and other diseases involving neurogenic inflammation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPERATIONAL NETWORKS IN THE AMYGDALA Principal Investigator & Institution: Cassell, Martin D.; Anatomy and Cell Biology; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2005 Summary: (provided by applicant): The amygdala is widely recognized as playing a critical role at the interface between emotion and behavior. Much of the interpretation of functional imaging, neuropsychological and pathological studies of the amygdala in anxiety, phobias, depression and drug and alcohol addiction, and the results of a large number of animal experiments, are framed in the context of a linear model of amygdala organization. In this model, inputs from the cortex and thalamus converge on the lateral and basolateral nuclei where learned associations are generated and expressed as autonomic and endocrine changes through the connections of the central, nucleus, the "output" nucleus of the amygdala. However, more and more clinical and experimental findings are becoming difficult to reconcile with this model. The experiments in this proposal are directed at the P.I.'s long term goal of developing a network-based model of amygdala organization with greater interpretative and predictive value. The experiments focus on the central extended amygdala (CEA) not as connecting the rest of the amygdala with autonomic/endocrine areas but as a basal ganglia-like structure involved in re-entrant circuits with the insular cortex, another area increasingly being associated with appetitive drives, emotion and psychiatric disorders. First, combinations of axon tracers will be used to identify the key nodes in re-entrant circuits through the CEA, including a possible "indirect" pathway involving the lateral hypothalamus. Second, immunochemical methods will be used to identify neurochemical compartments in the CEA and determine whether they are organized on the same lines as the nucleus accumbens. Finally, the reconstruction of axons derived from cortical and CEA neurons will be undertaken to examine the likely sequential processing of information by the amygdala network. Preliminary data indicate that the CEA, a socalled "output" structure may receive cortical/thalamic input before the lateral and basolateral nuclei. The experimental results should provide a strong basis for developing a second generation model of amygdala organization offering much greater interpretive value for experimental and clinical studies of psychiatric disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ORGANOCHLORINE EXPOSURE, GENETIC POLYMORPHISM AND PARKINSON'S DISEASE Principal Investigator & Institution: Berkowitz, Gertrud S.; Professor; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: (Taken from application) Parkinson?s disease (PD) is a progressive, disabling disorder of the central nervous system characterized by tremors at rest, muscle rigidity, slowness, imbalance and, in later stages, often dementia. It is caused by loss of neurons in the substantial nigra that produce dopamine. Approximately half a million Americans are estimated to be affected by PD. Recent data suggest that environmental
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exposure, possibly in concert with genetically determined vulnerabilities, contribute to causation of PD; particularly in patients with onset of disease above age 50. The study will examine 300 cases of PD whose diagnoses have been confirmed by strict, standardized criteria and 300 controls with "minor" neurologic disorders not involving the basal ganglia. A blood sample will be obtained and a detailed questionnaire will be administered to each case and control. The groups will be half male, half female. All eligible minority patients will be enrolled. Cases and controls will be matched on age, gender, and race. This proposal has two inter-related biomedically based, epidemiologic objectives. We propose to determine: 1) whether serum organochlorine levels and/or a past history of exposure to pesticides are elevated in patients with Parkinson s disease; 2) whether polymorphisms in specific enzymes related to pesticide metabolism are more common in patients with PD; and 3) whether there is evidence for a gene-environment interaction. A more exploratory objective is to evaluate whether diet, particularly intake of antioxidants, may protect against development of PD. To test the hypothesis that organochlorine levels, the most common type of chemical pesticide used between 1940 and 1970, are increased in PD patients, DDT, DDE, Dieldrin, and oxychlordane will be determined and compared between cases and controls. PCB, its congeners and transnonachlor will also be measured since these are organochlorine compounds as well. The gene polymorphism hypotheses will focus specifically on CYP2D6, GSTP1, and PON1. To evaluate the possible protective role of antioxidants, a detailed dietary history will be taken to obtain extensive information on usual antioxidant intake before diagnosis, including Vitamins A, C and E, carotenoids, lycopene, tocopherol and polyphenols (phytoestrogens). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOPHYSIOLOGY OF CHOREA Principal Investigator & Institution: Mink, Jonathan W.; Associate Professor; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 19-JUN-2000; Project End 31-MAY-2005 Summary: Chorea is a movement disorder that results from basal ganglia injury due to a variety of causes in children. Chorea is characterized by sudden, brief, involuntary muscle contractions causing movements that appear to flow from body part to body part in an unpredictable manner. Disorders associated with chorea include CNS infections, post-infectious and other autoimmune diseases, ischemia during cardiopulmonary bypass, 'extrapyramidal' cerebral palsy, a variety of toxic and acute metabolic processes, degenerative conditions, and inborn errors of metabolism. In many cases the cause is unknown. In diseases with well defined neuropathology, chorea has been associated with abnormalities in the striatum (caudate and putamen) and the subthalamic nucleus (STN). However, the fundamental pathophysiology of chorea is not known. This is due in part to the lack of non-primate models and in part to the difficulty of measuring involuntary movements in the primate models that do exist. Current medical treatment options for chorea are few, may have significant side effects, and are often ineffective. The proposed experiments will develop quantitative 3-dimensional kinematic measures of chorea and use them measure spatial and temporal properties of chorea in adults and children with different disorders. Focal pharmacologic manipulation of basal ganglia nuclei will be used in monkeys to produce chorea. The resulting chorea will be measured in the monkeys and compared to human chorea in order to validate the monkey models, especially with respect to childhood chorea. The monkey models will then be used to investigate the fundamental pathophysiology of chorea by recording the activity of individual globus pallidus internal segment neurons
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before and during chorea. Through a combination of neurophysiologic and kinematic techniques to study experimentally produced chorea, the prevailing hypotheses of chorea pathophysiology can be tested rigorously. There is strong potential to identify the fundamental mechanisms of chorea. Development of a non-invasive method to quantify chorea in children and in monkeys will be an important advance toward better characterization of the pathophysiology of involuntary movements and development of more effective medical therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHARMACOLOGY AND TOXICOLOGY OF METHAMPHETAMINE ABUSE Principal Investigator & Institution: Hanson, Glen R.; Acting Director; Pharmacology and Toxicology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2003; Project Start 01-AUG-1998; Project End 31-AUG-2006 Summary: (Applicant's Abstract) This is a Senior Scientist Award proposal for Dr. Glen R. Hanson. Dr. Hanson is a tenured professor in the Department of Pharmacology and Toxicology at the University of Utah. He has been active in drug abuse research for over 15 years and has made important contributions to elucidating: (a) the role of dopamine systems in neurotoxicity caused by amphetamine analogs; (b) the role of reactive oxygen species in mediating monoaminergic changes caused by amphetamine analogs; (c) the influence of the stimulants of abuse on neuropeptide systems; (d) the role of dopamine receptor subtypes in the regulation of extrapyrarnidal and limbic neuropeptide systems. Dr. Hanson currently devotes 40-50% of his time to research and student mentoring while 50-60% of his effort is occupied by teaching, departmental and college responsibilities. This Senior Scientist Award will allow Dr. Hanson to increase his research effort to approximately 80%. During the time of support by this award, he will direct research which tests the following principal hypotheses: (a) the generation of dopamine-related reactive oxygen species is a major contributor to the neurochemical deficits occurring in the striatal monoaminergic systems after high doses of methamphetamine (METH); (b) methcathinone, a relatively new designer amphetamine, exerts profound short-and long-term effects on extrapyramidal and limbic monoaminergic systems and has significant neurotoxic potential; (c) METH acutely and selectively alters the nature and function of the dopamine transporter in a reversible manner; (d) low and high doses of METH preferentially influence the indirect (striatalpallidal) and direct (striatal-nigral) efferent pathways to the basal ganglia output nuclei, respectively; (e) changes in neuropeptide systems occur in humans exposed to the potent stimulants of abuse much like that observed in rats after treatment with these same drugs. The increase in research time resulting from a Senior Scientist Award will allow Dr. Hanson to develop expertise in technologies new to his laboratory required to test these hypotheses, such as: (a) free radical analysis; (b) transporter function and ligand assays; (c) in situ hybridization for neuropeptide precursor mRNA. This award will help Dr. Hanson to mentor more effectively inexperienced researchers at the undergraduate, graduate, postdoctoral and young faculty levels as these developing scientists mature and establish themselves in neuroscience research in general, and drug abuse research in particular. In addition, as a mentor Dr. Hanson will be especially supportive of the involvement of underrepresented minorities in drug abuse research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PHYSIOLOGY OF ATP RELEASE IN CHRONIC PAIN Principal Investigator & Institution: Matsuka, Yoshizo; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2006 Summary: (provided by applicant) Chronic inflammatory and neuropathic pain is a problem of considerable clinical relevance. Understanding the mechanisms underlying development and maintenance of chronic pain would be a major step towards rational treatment of such pain conditions. Considerable evidence links chronic pain of neuropathic origin with increased excitability and abnormal signal generation in primary afferent neurons within sensory ganglia. Chemically-mediated cross-excitation between neurons in sensory ganglia has been proposed as one major mechanism by which abnormal discharges can be generated in pathological pain states. However, the identity of the chemical mediator of cross-excitation is unknown. Adenosine triphosphate (ATP) is released within sensory ganglia following neuronal activation and was shown to activate receptors on somata of sensory neurons. The overall goal of this proposal is to directly test the hypothesis that ATP is the chemical mediator of crossexcitation and to determine how release of ATP changes in pathological pain states. The specific aims are to: 1) determine the involvement of released ATP in cross-excitation of neurons within sensory ganglia, 2) determine the changes in basal and stimulus-evoked ATP release after peripheral inflammation, 3) determine the changes in basal and evoked ATP release after induction of sciatic neuropathy, 4) compare ATP release from different types of isolated and labeled DRG neurons. Cross-depolarization evoked by peripheral nerve stimulation will be measured during intracellular recordings from neurons in dorsal root ganglia (DRG). ATP receptors on sensory neurons will be manipulated by application of selective agonists and antagonists to influence evoked cross-depolarization. ATP release will be measured by the luciferin-luciferase assay in DRG perfusates. ATP release from acutely isolated DRG neurons will be measured using detector patches. These studies will be carried out first under normal conditions and then compared to results obtained after induction of a) peripheral inflammation, and b) peripheral neuropathy in rats. The acquired knowledge may lead to the development of novel therapeutics targeting abnormal excitability changes in sensory neurons. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PRESYNAPTIC NEUROCHEMICAL MARKERS Principal Investigator & Institution: Frey, Kirk A.; Professor of Radiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2003 Summary: Some markers of presynaptic cholinergic nerve terminals such as the enzyme choline acetyltransferase (ChAT) are reduced in the cortex of Alzheimer's disease (AD) patients. Similarly, reductions in dopaminergic indices in the basal ganglia are recognized in Parkinson's disease (PD). These neurochemical changes correlate with the severity of cognitive impairment in AD and with extrapyramidal features in PD. Such marker losses are widely assumed to reflect losses of basal forebrain cholinergic neurons and their terminal projects in AD and of substantial nigra dopaminergic neurons and their striatal terminals in PD. Results obtained in our laboratories indicate that a relatively new class of synaptic markers, vesicular neurotransmitter transporters, are quantitative markers of synaptic terminal losses in neuropathological conditions and are not affected by regulatory changes in response to altered synaptic activity or drug
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treatments. These transporters can now be measured in vitro with ligand binding and immunohistochemistry and in vivo with positron- or single photon emission computer tomography. We recently determined that the vesicular acetylcholine transporter (VAChT) in differentially preserved in AD cortex and hippocampus in comparison to reductions in ChAT activity. This contrasts with results in experimental animals where septo-hippocampal axotomy results in a complete loss of VAChT from the hippocampal formation. Combined, these results suggest that basal forebrain cholinergic neurons in AD are not as depleted as ChAT measures suggest, and that cortical cholinergic innervation may be better structural preserved than previously appreciated. Experiments in the current proposal will characterize further the postmortem neurochemical phenotypes of subcortical cholinergic and dopaminergic projection system in neurodegenerative dementing disorders. We will determine the relationships between cell body and nerve terminal losses in the basal forebrain-to-cerebral cortex cholinergic system and in the midbrain-to-striatum dopaminergic system, employing a combination of histological, ligand binding, immunohistochemical, and mRNA hybridization techniques. We anticipate that distinct, specific and inter-related patterns of cholinergic and dopaminergic pathologies will be found in AD, Lewy body dementias, and PD. These patterns may account for some apparent discrepancies among prior reports of neurochemical pathology in AD and related dementias, and may provide important insights into possible common versus differing pathophysiological mechanisms of dementing diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROTEOMICS OF MORPHINE RESPONSES OF THE BASAL GANGLIA Principal Investigator & Institution: Eberwine, James H.; Professor; Pharmacology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2006 Summary: The overall goal of this proposal is to advance a new and powerful paradigm in pulmonary physiology; one we call Image-Functional Modeling (IFM). Conceptually, IFM synthesizes imaging data and mechanical and ventilation function data taken in the same subject with anatomically specific three-dimensional models of the lung. Boston University, as the lead institution will partner with the Massachusetts General Hospital, Brigham and Women's Hospital, Tufts University School of Veterinary Medicine, and the University of Aukland to exploit IFM via the following imaging modalities: Positive Emission Tomography (PET), High Resolution Computer Tomography (HRCT), and Hyperpolarized Helium Magnetic Resonance Imaging (Hyp 3/He MRI). The IFM will be applied to asthma and to respiratory distress syndrome (RDS). Our specific aims are to:. Advance a 3D anatomically specific computational model of the lung that can predict overall and dynamic lung mechanical and ventilation function while permitting the imposition of a heterogeneous insult to explicit anatomic locations. This model will consist of a scaffold of modules across multiple biological scales resulting in an open source simulation resource for the general respiratory structure-function community. Synthesize our computational models with imaging and mechanical functional data taken simultaneously in the same subjects. The imaging data will quantify ventilation distribution and/or airway geometry while the mechanical function data will include standard clinical lung function indices (eg., spirometry) and dynamic lung function. Applications of IFM to asthma and RDS will quantify the likelihood of two hypotheses: a) The primary cause of functional degradation in both ventilation and mechanics during asthma lies within the smafl airways (d<2mm), namely, their constriction
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pattern; and b) During mechanical ventilation, setting the level of positive endexpiratory pressure to reduce dynamic heterogeneity will minimize risk of lung injury' while optimizing ventilation distribution. Perform a rigorous sensitivity analysis to a) examine the impact of local and distributed disease induced changes in geometry and the biomaterial properties on function; and b) predict the likely impact and outcome of specific clinical interventions or therapies on total and local lung function. The IFM paradigm represents a breakthrough in quantitative image interpretation and in model based understanding of lung function. Comprehensive and integrative new hypotheses and insights into lung pathophysiology and in medical practice will evolve in ways unachievable by considering any of these domains alone. The long term goal is to provide guidance on interventions such as pharmaceutics and mechanical ventilation, and to do so on a personalized basis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PSYCHOSTIMULANTS AND LENTIVIRAL INFECTION OF NEURAL CELL Principal Investigator & Institution: Mathes, Lawrence E.; Professor; Veterinary Clinical Sciences; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-MAY-2005 Summary: Methamphetamne (METH) is a mood-elevating, positively reinforcing drug of high abuse potential in humans. Continuous use of METH can lead to a number of adverse psychological, immunological, and permanent neurotoxicological effects. Species sensitivity to the neurotoxicological effects vary, but are uniform in creating degeneration of serotonergic and dopaminergic nerve terminals of subcortical structures. Increasingly greater numbers of HIV-1 infected individuals are known METH abusers throughout the world. The synergistic effects of chronic METH abuse and HIV-1 infection are presently poorly understood. Both conditions have detrimental affects on the immune system and cause a progressive, subcortical mediated neurodegeneration. The cat is a well-suited animal model to study the synergistic effects of chronic METH abuse and HIV-1 infection. Cats exhibit a similar metabolism of and sensitivity to METH as humans. Moreover, a feline model of neuroAIDS is welldocumented, resulting in a progressive, subcortical mediated neurodegeneration associated with immunodeficiency, behavioral disturbances, and neuronal loss after feline immunodeficiency virus (FIV) infection. Thus, the overall objective of this study is to evaluate the synergistic effects of FIV infection and chronic METH with acute "binges" on immune function and viral interaction, neurobehavior and neurophysiology, and neurodegeneration. The overall hypothesis is that FIV and METH are synergistic in enhancing viral load, immunosuppression, altered behavior, and subsequent neurodegeneration. Three specific aims will be studied: 1. Determine the pharmacokinetics patterns, immune function and viral load prior to and after METH administration to FIV infected cats over a 6 month period; 2. Determine the behavioral, physiologic, and neurochemical neurotoxicity of chronic METH administration in uninfected and FIV infected cats over a 2 year period; and 3. Determine the interaction of METH and FIV on glutamate uptake, release, and glutatmate metabolism as related to excitotoxic neuronal loss in the basal ganglia. The goal is to elucidate on the effects and mechanisms of METH and HIV-1 interaction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGIONAL PATTERNING IN THE VENTRAL TELENCEPHALON Principal Investigator & Institution: Fishell, Gordon J.; Associate Professor; Cell Biology; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 01-APR-2000; Project End 31-MAR-2004 Summary: Applicant's abstract reproduced verbatim): Subsequent to the end of gastrulation a series of developmental steps transform the anterior most neural plate from an apparently unpatterned sheet of neural epithelium into the highly order structure that gives rise to the mature telencephalon. These patterning events result in the telencephalon being divided into three major domains from dorsal to ventral, the cortex, the LGE (which gives rise to the striatum) and the MGE (which gives rise to the globus pallidus). Studies by a number of groups, including our own, have begun to shed light on the molecular and cellular mechanisms underlying how these regions are established. Analysis of Shh mutant embryos has demonstrated that this gene is essential for the formation of the basal ganglia. Less clear is the mechanism by which this is mediated. Insight into this process has come from in vitro studies in my laboratory that suggest that Shh requires the addition of acyl groups for activity within the telencephalon but not in the spinal cord. In this application we propose to test the region specific requirement for the acylation of Shh in vivo, through gain of function and loss of function analysis. We have also shown that the telencephalon undergoes a progressive change in its competence to respond to Shh and that these changes in competence play a key role in dorsoventral patterning within the telencephalon. Specifically, early exposure of naive telencephalon to Shh results in Nkx2.1 induction, later exposure to Shh induces Gsh-2 expression. We will use both genetics and ectopic expression to study the role of these genes. In the proposed studies, we will also determine whether these changes in Shh responsiveness are mediated by an extrinsic or cell-autonomous mechanism, as well as examine the possible roles of factors that may cooperate with Shh, such as BMP, Wnt and FGF proteins. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RNAI TARGETING OF KV3 CHANNELS IN BASAL GANGLIA DISEASE Principal Investigator & Institution: Tkatch, Tatiana; Physiology; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2006 Summary: (provided by applicant): Parkinson's disease (PD) is a neurodegenerative disorder characterized by impairment of motor function. It affects about 1 in 1000 adults, rising exponentially after the age of fifty. At present there is no treatment for PD shown to definitively attenuate disease progression. Even temporal correction of symptoms extending the period of physical mobility is considered valuable. We suggest to test a new strategy to relieve motor symptoms of the Parkinson's disease. The abnormal correlated rhythmic activity in the globus pallidus (GP) and subthalamic nucleus (STN) are believed to underlie bradykinesia and tremor of PD patients. A specific set of membrane conductances in GP and STN neurons enable such activity. Recent work by our group has shown that high frequency burst discharge in GP and STN neurons is dependent upon their expression of a combination of voltage-dependent Kv3 K+ channel subunits. These neurons form heteromeric channels containing Kv3.1 and Kv3.4 subunits. These heteromeric channels are very efficient at repolarizing spikes - keeping them very brief - and then deactivating after the spike to allow the next spike to occur quickly. Eliminating the Kv3.4 subunit from these channels diminishes the
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repolarizing efficiency of the channels, resulting in lower maximal discharge rates. Thus our goal is to test the hypothesis that the suppression of Kv3.4 subunit in GP/STN neurons will dramatically reduce pathological, high frequency burst discharge leading to symptomatic relief in PD models and patients. Kv3.4 is an excellent target for gene therapy approaches since its expression is highly specific for fast spiking neurons and the firing of non-targeted neurons in GP/STN surrounding areas should not be affected. We propose to use lentivirus vector to deliver small interfering RNA (siRNA) designed to trigger the degradation of Kv3.4 mRNA in GP and STN neurons. The proposed specific aims will allow development of the technology that is necessary for testing of our hypothesis in the animal models of PD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE NEUROTOXICITY
OF
INFLAMMATION
IN
MANGANESE-INDUCED
Principal Investigator & Institution: Filipov, Nikolay M.; Assistant Professor; Ctr for Environmental Hlth Sci; Mississippi State University P. O. Box 6156 Mississippi State, Ms 39762 Timing: Fiscal Year 2002; Project Start 27-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant) Studies suggest that environmental contaminants, include manganese (Mn), may contribute to Idiopathic Parkinson?s Disease (IPD), but the etiology of this disease still remains elusive. Two major sources of Mn pollution in the United States arise from the reintroduction of the fuel additive methylcyclopentadienyl manganese tricarbonyl and the widespread use of Mncontaining fungicides (maneb). Recently, the investigators obtained evidence that Mn, a neurotokicant causing Parkinson?s Disease-like symptoms, increases proinflammatory cytokines and nitric oxide production by activated microglia in vitro. These findings suggest that (i) inflammation plays a role in Mn-induced neurotoxicity, and (ii) Mn exposure may be a contributing factor (via enhanced production of inflammatory mediators) to IPD. The research proposed here will explore these possibilities utilizing both in vitro and in vivo approaches. Additional studies will begin to delineate the mechanism(s) by, which Mn enhances the inflammatory response in the brain. It is hypothesized that exposure to Mn, enhances activation of microglia which are disproportionately distributed in the brain and as a result, over-production of proinflammatory cytokines and nitric oxide occurs with the final outcome being selective neuronal loss in the basal ganglia. Furthermore, exposure to Mn in the context of an inflammatory stimulus would potentiate the dopaminergic neuronal damage in the 1-methyl-4-phenyl-1,2,3,4- tetrahydropyridline (MPTP) mouse model of PD. Microglial cell line (N9), as well as primary microglia, will be used to determine whether Mn speciation plays a role in the increased inflammatory response. Microglial (N9)dopaminergic (PC 12) cell line co-cultures, as well as mesencephalic primary cultures will be used in vitro studies and the effects of Mn in the presence of a microglial activator (endotoxin, LPS) on neuronal cell death will be assessed. Additionally, Mn influence on the sensitivity of the dopaminergic neurons to MPTP under the same in vitro conditions will be evaluated. C57BL/6 (MPTP-sensitive) and CD-1 (MPTPresistant) mice will be used for in vivo studies and animals will be treated similarly to the cell cultures in the in vitro studies. After short (14 days) exposure to Mn, some animals will be challenged with MPTP, and the degree of basal ganglia damage, as well as microglial activation will be assessed. Successful completion of the proposed research will help revealing the role of inflammation in Mn neurotoxicity and, more importantly, establish a mechanism by which environmental contaminants may contribute to the
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etiology of IPD. The long-term goal of the proposed studies is to understand the role of microglia and environmental contaminants in neurodegenerative diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE OF MANGANESE IN NEURODEGENRATIVE DISEASE Principal Investigator & Institution: Smith, Donald R.; Associate Professor; Environmental Studies; University of California Santa Cruz 1156 High St Santa Cruz, Ca 95064 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): Recent studies have shown that chronic exposures to manganese (Mn) are associated with an increased risk for the development of neurodegenerative diseases, such as Parkinsonism. Concern over the potential neurotoxicity of low but chronic Mn exposure has increased in light of the incorporation of MMT into gasoline. The effects of Mn exposure in in vivo rodent models has focused on Mn-induced depletion of striatal dopamine, whereas non-human primate studies have more commonly shown gliosis in the globus pallidus. Also, most studies have utilized relatively high Mn exposures, while only a few have investigated the effects of chronic low-level Mn exposures. Here we are proposing that the locus of Mn toxicity may depend on the total cumulative Mn dose, such that more sensitive GABAergic systems of the globus pallidus are targeted at lower relative doses, while dopaminergic systems of the nigro-striatal pathway become involved at higher doses. To validate this, there is a need to investigate the effects of Mn on specific brain nuclei and neurotransmitter systems as a function of Mn exposure regimens in order to better characterize the overall susceptibility of the basal ganglia to Mn effects. Moreover, there is justified concern that increased chronic low-level Mn exposure may further undermine the functionality of the basal ganglia in susceptible populations in the early stages of neurodegenerative disease, and accelerate the emergence of neuromotor dysfunction. The specific aims of this study are to: (1) Determine the progression of Mn effects on brain regional Mn distribution, and neurochemical and neuromotor function, across different durations and low level doses of Mn exposures in a whole animal rodent model. And (2) Determine the effect(s) and underlying interaction(s) of Mn exposure on neurotoxicity and neuromotor performance in a rodent model of asymptomatic Parkinsonism, as a model of a susceptible population. These Aims will be pursued through several sub-aims focusing on the following major outcomes: (i) A Functional Observational Battery (FOB) of neuromotor performance; (ii) Particle induced X-ray emission (PIXE) analyses of in situ brain regional Mn levels; (iii) Neurochemical measures of GABAergic and dopaminergic metabolism/status in specific brain regions, and; (iv) Investigation of specific mechanisms underlying the Mn - GABAergic effect using cell culture models. These proposed studies will significantly extend our knowledge of chronic low level Mn neurotoxicity, by pursuing a unifying hypothesis of action of low-level chronic Mn exposure, and by investigating neurochemical and neuromotor outcomes of Mn exposure in conjunction with a moderate degree of sub-threshold Parkinsonism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SEROTONIN CONTROL MECHANISMS OF BASAL GANGLIA FUNCTION Principal Investigator & Institution: Walker, Paul D.; Associate Professor; Anatomy and Cell Biology; Wayne State University 656 W. Kirby Detroit, Mi 48202
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Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (Verbatim from the Applicant's Abstract) Attempts to develop new and effective treatments for movement disorders such as Parkinson's disease have been hampered by an insufficient knowledge of how basal ganglia receptor systems adapt to the consequences of dopamine depletion. This research focuses on determining the role of upregulated serotonin 2A receptors, which we hypothesize provide a mechanism for serotonin to exert greater control over basal ganglia transmission and locomotor function under conditions of dopamine depletion. Our preliminary studies indicate that the target of the serotonin 2A receptor mechanism is the DIRECT striatonigral pathway which utilizes tachykinin neuropeptides colocalized with GABA. New experiments of this application will test the central hypothesis that: upregulated serotonin 2A receptor signaling provides a mechanism for serotonin to enhance striatonigral transmission under conditions of dopamine depletion which influences basal ganglia function and animal behavior. In Specific Aim 1, we will determine the functional consequences of an upregulated serotonin 2A receptor system on serotonin signal transduction within the dopamine depleted striatum by measuring serotonin 2A receptor binding, its linkage to phosphoinositol hydrolysis, its modulation of striatal membrane excitability, and its ability to trans-synaptically regulate striatal tachykinin and GABA expression. In Specific Aim 2, we will determine if tachykinin striatonigral neurons react to the stimulation of upregulated serotonin 2A receptors in the dopamine depleted animal by increasing tachykinin and GABA transmission in the substantia nigra. We will also study the impact of this regulation on locomotor behavior. Finally, in Specific Aim 3, we will determine how an upregulated serotonin 2A receptor system influences the ability of the striatonigral system to regulate basal ganglia dopamine and GABA metabolism, and how these systems influence behavioral recovery of the dopamine depleted animal. Information obtained from these studies will contribute to a better understanding of basal ganglia function and may change how serotonin pathways are considered when designing new pharmacological strategies for diseases which affect dopamine transmission. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP DEPRIVATION, EEG, & FUNCTIONAL MRI IN DEPRESSION Principal Investigator & Institution: Clark, Camellia P.; Psychiatry; University of California San Diego La Jolla, Ca 920930934 Timing: Fiscal Year 2002; Project Start 20-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from applicant's abstract): The objective of this 5-year Mentored Clinical Scientist Development Award for Cametlia Clark, M.D. is to develop the candidate's expertise in functional magnetic resonance imaging (MRI) while building on her previous skills in neuroimaging and sleep research. This goal will be accomplished through a carefully designed training plan involving didactic courses and mentorship by experts (at and outside UCSD) in basic neuroscience, structural MRI, functional MRI (fMRI) physics, sleep and affective disorders research, and statistics as well as intensive instruction in fMRI research in a setting featuring state-of-the-art scanners, innovative pulse sequences (particularly perfusion-weighted), and the first fMRI studies utilizing sleep deprivation (SD) to study cognitive function in normal subjects (published recently in Nature and NeuroReport. This training program will enable Dr. Clark to complete the transition to independent investigator and provide the foundation for a long-term research program utilizing fMRI and polysomnography to investigate brain function in affective disorders. The research plan utilizes one night of partial SD (PSD), an excellent model of antidepressant treatment which is fast-acting, and does not require
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medications. The applicants hypothesize: I) depressed responders' baseline perfusion signal intensity in the ventral anterior cingulate (BA 25 and ventral 24) / medial prefrontal cortical (BA 32) areas will be greater than that of nonresponders and controls; 2) following PSD, perfusion in the ventral anterior cingulate (BA 25 and ventral 24) / medial prefrontal cortical (BA 32 and 10) areas will significantly decrease in responders only. The applicants will also look for between-groups and within-groups differences in other regions where functional abnormalities have been reported in depression, including (but not limited to) dorsal anterior cingulate, dorsolateral prefrontal cortices, medial frontal cortices, amygdala, hippocampus, thalamus, and basal ganglia. Finally, the applicants will look for possible between-groups structural MRJ differences, which could potentially confound fMRI analyses. FMRI perfusion data will be analyzed by the analysis of variance algorithm in AFNI (Analysis of Functional Neural Images) software. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STN STIMULATION--NEURAL CONTROL OF MOVEMENT AND POSTURE Principal Investigator & Institution: Corcos, Daniel M.; Professor; School of Kinesiology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Applicant's Abstract): High frequency stimulation of the subthalamic nucleus (STN) dramatically improves all of the clinical motor symptoms of Parkinson's Disease (PD). However, there are limited objective data available to determine which characteristics of movement and posture are affected by STN stimulation, and by what neural mechanisms this is accomplished. The long-term objective of this application is to obtain objective neurophysiological data relating to the mechanisms by which effective STN stimulation alters the spatial and temporal patterns of activity mediating planned movement and posture in humans. Patients in whom STN surgery is successful, as defined by a 30% reduction in the motor score of the Unified Parkinson's Disease Rating Scale, will take part in a series of experiments designed to investigate the neural control of movement and posture. The experiments in Aim I will use electromyographic (EMG) and motion analysis techniques to identify which aspects of strength, movement and standing balance are improved, worsened or unchanged by STN stimulation. The effects of STN stimulation will also be compared with the effects of medication on the control of strength and movement. The hypothesis is that neither STN stimulation nor medication normalizes the control of movement, and STN stimulation does not normalize the control of standing balance. Aim 2 will use electroencephalographic (EEG) techniques to test whether STN stimulation-induced changes in movement and gait initiation are accompanied by changes in the spatial and temporal patterns of cortical activity in response to both internally and externally generated cues to move. The hypothesis is that STN stimulation does not normalize the pathways that are normally influenced by the STN but does allow other pathways to compensate better. Aim 3 will combine EEG techniques with stimulation through the quadripolar electrodes implanted in the region of the STN to examine the pathways activated by effective STN stimulation. The findings of the proposed experiments will advance our understanding of the role of the STN in motor function, assist in the development of improved models of the role of the basal ganglia in the control of movement and posture, and thereby contribute to improved treatments for Parkinson's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE BASAL GANGLIA SYSTEM IN VOCAL COMMUNICATION Principal Investigator & Institution: Jarvis, Erich D.; Assistant Professor; Neurobiology; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 22-JAN-2002; Project End 31-DEC-2004 Summary: provided by applicant) In the past several years, songbirds have increasingly become a useful model system for studying the functional role of the basal ganglia pathway loop in complex behaviors such as learned vocal communication. In young birds, the vocal part of the basal ganglia pathway is required for song learning. In adults who have learned their songs, it is not necessary for production of learned vocalizations, but shows dramatic changes in gene activation depending upon the social context in which vocalizing occurs. This context-dependent vocal gene activation lead to a number of intriguing testable hypotheses of the basal ganglia's functional role in adult vocal communication. These ranged from 1) regulating gene expression and activity of the vocal motor pathway to 2) generating on-line complexity of the singer's vocalizations. The goals of the experiments in this proposal are to test these hypotheses and, in doing so, to determine the basic function of the vocal basal ganglia loop in learned vocal communication. Since the loop is built within a circuit that is conserved in the vertebrate brain, it is believed that the underlying mechanisms discovered will generally apply to complex social behaviors such as learned vocal communication in humans. However, since vocal learning is a very rare trait, as it is only found in 3 groups of mammals (humans, dolphins, and bats) and 3 groups of birds (songbirds, hummingbirds and parrots), with songbirds being the most studied animal model, the results of this proposal are expected to generate unique insight into higher order brain function, and insight into diseases that affect speech, language, and cognitive processes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE CALCIFICATION
GENETICS
OF
IDIOPATHIC
BASAL
GANGLIA
Principal Investigator & Institution: Geschwind, Daniel H.; Director, Neurogenetics Program; Neurology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 05-FEB-2001; Project End 31-JAN-2005 Summary: (adapted from applicant's abstract):The core features of idiopathic basal ganglia calcifications (IBGC) or Fahr's disease are dystonia, parkinsonism and neurobehavioral abnormalities that are associated with calcifications visible on CT scan of the brain. Familial IBGC shows mostly an autosomal dominant mode of inheritance. The investigators have mapped a locus on chr.14q in one large multiplex family. In two other families linkage to chr.14 has been excluded, demonstrating genetic heterogeneity. The minimal critical region (MCR) on chr.14 is 15 or probably 10cM. The investigators propose to narrow down the MCR by collecting additional family members of the original pedigree as well as other families. Physical mapping and candidate screening for mutations will be pursued as the region is narrowed to identify the IBGC gene. A genome scan will be performed in families who are not linked to the chr.14 locus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE NEURAL BASIS OF INSTRUMENTAL ACTION Principal Investigator & Institution: Balleine, Bernard W.; Assistant Professor; Psychology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024
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Timing: Fiscal Year 2003; Project Start 15-JAN-1997; Project End 31-MAY-2008 Summary: (provided by applicant): The organization of goal-directed action is influenced significantly by the agent's ability to inhibit or gate responses to sensory, motor and cognitive information. Deficits in these central inhibitory mechanisms are manifest in a number of neuropsychiatric syndromes characterized by disorders of 'voluntary' movement, e.g. Parkinson's disease, and intrusive involuntary movement, e.g. Tourette's syndrome and Huntingdon's disease. These cases make it clear that the capacity for goal-directed action is highly adaptive, indeed it is this capacity that allows us and other animals to control the environment in the service of our needs and desires. Nevertheless, although research into the physiological systems that subserve learning processes in humans and other animals has been of ongoing concern to the neuroscience research community, the neural basis of instrumental action is very poorly understood. The broad, long term objective of the current project is, therefore, to understand the neural mechanisms that control the learning and performance of goal directed or instrumental actions. Over the last decade striking advances have been achieved in our understanding of the behavioral determinants of instrumental conditioning in animals. Specifically, instrumental performance has been found to reflect the integration of (i) representations of the relations between an action and its consequences; with (ii) representations of the incentive value of those consequences. Powerful behavioral procedures will be used to focus on the role of cortico-striatal interactions and feedback to cortex via pallidal and limbic structures in processes involved in the representation of the relation between an action and its consequences. In other experiments, the role of parallel interactions between insular cortex and basal forebrain structures in the representation of the incentive or 'goal' value of the instrumental outcome will be assessed. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOWARD A UNIFIED MODEL OF COGNITIVE CONTROL Principal Investigator & Institution: O'reilly, Randall Charles.; Associate Professor; Psychology; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by applicant): The overarching goal of the proposed research is to understand how the brain performs cognitive control. By cognitive control, we mean the ability of the cognitive system to flexibly control its own behavior in response to task demands or other contingencies, favoring the processing of task-relevant information over other sources of competing information, and mediating task-relevant behavior over habitual or otherwise prepotent responses. There is virtually universal agreement that the prefrontal cortex (PFC) plays a critical role in cognitive control. However, exactly what it does and how it does it, in terms of concrete neural mechanisms, remain considerably more controversial questions. Explicit computational models that incorporate biological mechanisms can provide a powerful means of testing theoretical ideas about the biological basis of cognitive control. However, existing models have each only simulated one or a few phenomena, leaving open questions about their general applicability across the entire domain of cognitive control. We propose to address this limitation by applying a single computational model that includes critical features of the underlying neurobiology (including the basal ganglia (BG) and its interactions with the PFC) to a wide range of benchmark behavioral and neural phenomena. This model includes powerful learning mechanisms that should produce intelligent, controlled behavior without relying on the kind of homunculus that often lies behind theories of cognitive control. Specific Aim 1: Modeling Behavioral and
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Neural Data. We test the sufficiency of our framework by evaluating whether a single instantiation of the model, trained on a single large corpus of tasks, can simulate a wide range of benchmark data in cognitive control, and we use this model to make a number of testable predictions. Specific Aim 2: Nature and Learning of PFC/BG Representations. We address the fundamental question: how can people quickly adapt to performing novel cognitive tasks, when it takes monkeys months of highly-focused training to learn a single new task? We hypothesize that people develop an extensive repertoire of basic cognitive operations throughout the long developmental period into adulthood, and can rapidly and flexibly combine them to solve novel tasks. Demonstrating this principle in an explicit computational model will have important implications for understanding human intelligence, education, and development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISEASE
TRANSGENIC
XENOTRANSPLANTS
FOR
HUNTINGTON'S
Principal Investigator & Institution: Isacson, Ole; Professor; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2002; Project Start 01-JAN-1992; Project End 31-MAR-2004 Summary: (Verbatim from the Applicant's Abstract) Brain cell transplantation research has shown that structural and functional repair of the adult brain is possible. We are testing the functional hypothesis that embryonic striatal neurons can replace neurons lost in adult primate striatum and improve signs of Huntinton's disease (HD). The lack of an optimal human donor cell source in a clinical scenario has led us to utilize zenogeneic (here transgenic pig) embryonic donor cells. Our preliminary in vivo data show that successful xenografts survival in the primate brain requires immunosuppression by cyclosporine, azathiopirne, methylprednisolone and complement inhibition (CD59 transgenic donor tissue and monoclonal antibodies against complement C5). To test the functional hypothesis, we proposed the following experiments: We will transplant CD59 complement aggregation inhibitor expressing transgenic porcine fetal striatal (E35 LGE) cells to the caudate-putamen of non-human primate (Macaca mulatta) with neuronal loss similar to that seen in HD. To determine how functional recovery depends on survival and growth of porcine striatal transplants, we will collect physiological in vivo data by PET/MRI/MRS and behavioral data by examining motor and cognitive function. The physiological analysis of LBE graft function by in vivo imaging and behavioral assays is followed by detailed morphological studies. Combine, these studies will provide essential data on the relationship between structural and functional integration of embryonic neuronal xenografts in a HD primate model. These experiments will improve our knowledge of basal ganglia function and plasticity, as well as determine parameters for optimal cell transplantation in patients with neurological disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: UCLA CENTER FOR THE STUDY OF PARKINSON'S DISEASE Principal Investigator & Institution: Chesselet, Marie-Francoise S.; Charles H. Markham Professor of Neurolog; Brain Research Institute; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-1999; Project End 31-JUL-2004 Summary: The UCLA Center for the Study of Parkinson's Disease will use an integrated multidisciplinary approach to elucidate the effects of nigrostriatal lesions and treatments
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of Parkinson's disease on the molecular and cellular characteristics of the subthalamic nucleus. This region of the basal ganglia has recently emerged as an important focus for the development of novel therapeutic strategies for the disease. The goal of the Center will be to identify new molecular targets for non-invasive pharmacological treatments for Parkinson's disease. The techniques of molecular neuroanatomy, slice electrophysiology, in vivo microdialysis and behavioral analysis will be used in four animal models: I) rats with nigrostriatal lesions; 2) lesioned rats treated with L-DOPA; 3) lesioned rats with chronic deep brain stimulation of the subthalamic nucleus; 4) lesioned rats with implanted OABA producing cells in the subthalamic nucleus. Key findings will be examined with molecular anatomical techniques in post-mortem human brain. Research in the Center will be supported by an Administrative and Communication core. In addition, an Animals and Neuropathology (Core B), Molecular Biology (Core C), and Neuroengineering (Core D) cores will provide standardized research tools for all projects and develop new cutting edge technology to enhance research in the Center. Core B will provide standardized surgical, behavioral, histological and neurochemical procedures for all the animal models examined in the Center, and will collect well characterized brains form patients with Parkinson's disease for study of the subthalamic nucleus. Core C will provide all projects with GABA-producing cells for in vivo transplantation, and will identify changes in gene expression with DNA microarray technology. Core D will develop and manufacture deep brain stimulation probes for rats and develop miniaturized probes for measuring neurotransmitter release. Interactions between the Center and clinical investigators in the Movement Disorder Program at UCLA will provide an ideal conduit for the rapid translation of research findings into clinical applications. The Center will provide a dynamic training environment that will expand the research capabilities of scientists at all career levels and their trainees. The Center will facilitate the participation of new investigators across the UCLA campus in research on Parkinson's disease and will reinforce the existing interactions between basic and clinical research on Parkinson's disease at UCLA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VISUAL TARGET SELECTION FOR SACCADIC EYE MOVEMENTS Principal Investigator & Institution: Basso, Michele A.; Physiology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Natural visual scenes require individual objects to be identified for further processing or to serve as targets for impending movements. Much work in the visual system has shown that competitive mechanisms are involved in the selection of objects of interest and in the filtering out of objects not of interest. Eye movement systems are faced with a similar selection problem since only one eye movement can be made at a time and visual scenes contain many possible targets. My long - term goal is to understand how the brain identifies targets of interest and how or whether this information is passed to motor systems. My objective in this proposal is to determine whether the organization of target selection mechanisms for the saccadic eye movement system, responsible for rapidly realigning the direction of sight, is similar to what appears to be prominent in visual perceptual systems. Specifically, I propose to test three hypotheses; first, that superior colliculus neurons (SC, a structure critically involved in saccadic eye movement generation) show competitive interactions like those seen in visual cortical regions and that these interactions change dynamically as saccade onset approaches (Specific Aim 1). Second, those stimulus-stimulus interactions within the SC are modulated by top-down mechanisms (Specific Aim 2), and third, that
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neurons within the basal ganglia (a set of structures with direct inhibitory inputs to the SC) contain activity reflecting the process of target selection for saccades (Specific Aim 3). The results of the proposed experiments will provide an important framework for understanding volitional movements of the eyes and perhaps other movement systems as well. In addition, by understanding how higher perceptual processes contribute to the production of volitional movements, we will have a more clear understanding of the root of a number of enigmatic symptoms that are not "purely motor." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “basal ganglia” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for basal ganglia in the PubMed Central database: •
Anatomical relationship between the basal ganglia and the basal nucleus of Meynert in human and monkey forebrain. by Haber S.; 1987 Mar; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=304439
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Modeling facilitation and inhibition of competing motor programs in basal ganglia subthalamic nucleus --pallidal circuits. by Rubchinsky LL, Kopell N, Sigvardt KA.; 2003 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=283608
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The Differential Role of Premotor Frontal Cortex and Basal Ganglia in Motor Sequence Learning: Evidence From Focal Basal Ganglia Lesions. by Exner C, Koschack J, Irle E.; 2002 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=187585
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The neostriatal mosaic: compartmental distribution of calcium-binding protein and parvalbumin in the basal ganglia of the rat and monkey. by Gerfen CR, Baimbridge KG, Miller JJ.; 1985 Dec; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=391521
3 4
Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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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 basal ganglia, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “basal ganglia” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for basal ganglia (hyperlinks lead to article summaries): •
A basal ganglia inspired model of action selection evaluated in a robotic survival task. Author(s): Girard B, Cuzin V, Guillot A, Gurney KN, Prescott TJ. Source: J Integr Neurosci. 2003 December; 2(2): 179-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15011270
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A diffusion tensor MRI study of basal ganglia from patients with ADEM. Author(s): Holtmannspotter M, Inglese M, Rovaris M, Rocca MA, Codella M, Filippi M. Source: Journal of the Neurological Sciences. 2003 January 15; 206(1): 27-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12480081
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A possible mechanism for the dopamine-evoked synergistic disinhibition of thalamic neurons via the "direct" and "indirect" pathways in the basal ganglia. Author(s): Sil'kis IG. Source: Neuroscience and Behavioral Physiology. 2002 May-June; 32(3): 205-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12135331
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A role of the basal ganglia in movement: the effect of precues on discrete bidirectional movements in Parkinson's disease. Author(s): Johnson AM, Vernon PA, Almeida QJ, Grantier LL, Jog MS. Source: Motor Control. 2003 January; 7(1): 71-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12536163
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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•
A SEEG study of ERP in motor and premotor cortices and in the basal ganglia. Author(s): Rektor I, Kaiiovsky P, Bares M, Brazdil M, Streitova H, Klajblova H, Kuba R, Daniel P. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 March; 114(3): 463-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12705427
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Action monitoring, error detection, and the basal ganglia: an ERP study. Author(s): Falkenstein M, Hielscher H, Dziobek I, Schwarzenau P, Hoormann J, Sunderman B, Hohnsbein J. Source: Neuroreport. 2001 January 22; 12(1): 157-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11201078
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Activation of basal ganglia loops in idiopathic Parkinson's disease: a PET study. Author(s): Thiel A, Hilker R, Kessler J, Habedank B, Herholz K, Heiss WD. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 November; 110(11): 1289-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628193
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Activation of cerebellum and basal ganglia on volitional swallowing detected by functional magnetic resonance imaging. Author(s): Suzuki M, Asada Y, Ito J, Hayashi K, Inoue H, Kitano H. Source: Dysphagia. 2003 Spring; 18(2): 71-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12825899
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Activity patterns in a model for the subthalamopallidal network of the basal ganglia. Author(s): Terman D, Rubin JE, Yew AC, Wilson CJ. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 April 1; 22(7): 2963-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923461
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Actor-critic models of the basal ganglia: new anatomical and computational perspectives. Author(s): Joel D, Niv Y, Ruppin E. Source: Neural Networks : the Official Journal of the International Neural Network Society. 2002 June-July; 15(4-6): 535-47. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12371510
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Acute necrotizing encephalopathy presenting as a basal ganglia syndrome. Author(s): Ravid S, Topper L, Eviatar L. Source: Journal of Child Neurology. 2001 June; 16(6): 461-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11417619
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Akathisia induced by necrosis of the basal ganglia after carbon monoxide intoxication. Author(s): Stuppaeck CH, Miller CH, Ehrmann H, Fleischhacker WW, Felber S, Poewe W. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1995 March; 10(2): 229-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7753072
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Alterations in m-RNA expression for Cu,Zn-superoxide dismutase and glutathione peroxidase in the basal ganglia of MPTP-treated marmosets and patients with Parkinson's disease. Author(s): Kunikowska G, Jenner P. Source: Brain Research. 2003 April 11; 968(2): 206-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12663090
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An MRI study of basal ganglia volumes in first-episode schizophrenia patients treated with risperidone. Author(s): Lang DJ, Kopala LC, Vandorpe RA, Rui Q, Smith GN, Goghari VM, Honer WG. Source: The American Journal of Psychiatry. 2001 April; 158(4): 625-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11282699
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Anatomical MRI study of basal ganglia in bipolar disorder patients. Author(s): Brambilla P, Harenski K, Nicoletti MA, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC. Source: Psychiatry Research. 2001 April 10; 106(2): 65-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11306247
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Anatomical MRI study of basal ganglia in major depressive disorder. Author(s): Lacerda AL, Nicoletti MA, Brambilla P, Sassi RB, Mallinger AG, Frank E, Kupfer DJ, Keshavan MS, Soares JC. Source: Psychiatry Research. 2003 November 30; 124(3): 129-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14623065
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Apoptosis in the basal ganglia of the developing human nervous system. Author(s): Itoh K, Suzuki K, Bise K, Itoh H, Mehraein P, Weis S. Source: Acta Neuropathologica. 2001 February; 101(2): 92-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11271378
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Arteriovenous malformations in the basal ganglia region: Gamma Knife radiosurgery as first choice treatment in selected cases. Author(s): Crocco A. Source: Journal of Neurosurgical Sciences. 2002 June; 46(2): 43-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12232548
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Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia. Author(s): Okamoto K, Ito J, Ishikawa K, Morii K, Yamada M, Takahashi N, Tokiguchi S, Furusawa T, Sakai K. Source: Neuroradiology. 2002 May; 44(5): 389-94. Epub 2002 February 16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12012122
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Autoimmunity and the basal ganglia: new insights into old diseases. Author(s): Dale RC. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 March; 96(3): 18391. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12615982
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Balance of transmitter activities in the basal ganglia loops. Author(s): Schmidt WJ. Source: Journal of Neural Transmission. Supplementum. 1995; 46: 67-76. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8821042
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Basal ganglia and functions of the autonomic nervous system. Author(s): Pazo JH, Belforte JE. Source: Cellular and Molecular Neurobiology. 2002 December; 22(5-6): 645-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12585684
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Basal ganglia and supplementary motor area subtend duration perception: an fMRI study. Author(s): Ferrandez AM, Hugueville L, Lehericy S, Poline JB, Marsault C, Pouthas V. Source: Neuroimage. 2003 August; 19(4): 1532-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12948709
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Basal ganglia and thalamic tumours: an imaging approximation. Author(s): Garcia-Santos JM, Torres del Rio S, Sanchez A, Martinez-Lage JF. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2002 August; 18(8): 412-25. Epub 2002 June 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12192501
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Basal ganglia calcification and psychotic symptoms in the very old. Author(s): Ostling S, Andreasson LA, Skoog I. Source: International Journal of Geriatric Psychiatry. 2003 November; 18(11): 983-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618548
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Basal ganglia calcifications in childhood. Author(s): Sato Y. Source: Semin Pediatr Neurol. 2003 March; 10(1): 96-102. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12785753
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Basal ganglia hemorrhagic ablation associated with temporary suppression of obsessive-compulsive symptoms. Author(s): Yaryura-Tobias JA, Neziroglu F. Source: Revista Brasileira De Psiquiatria (Sao Paulo, Brazil : 1999). 2003 March; 25(1): 402. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12975678
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Basal ganglia involvement in a child with cat-scratch disease. Author(s): Anbu AT, Foulerton M, McMaster P, Bakalinova D. Source: The Pediatric Infectious Disease Journal. 2003 October; 22(10): 931-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14579820
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Basal ganglia lesions in 'Pick complex': a topographic neuropathological study of 19 autopsy cases. Author(s): Tsuchiya K, Ikeda K. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. 2002 December; 22(4): 323-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12564774
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Basal ganglia N-acetylaspartate correlates with the performance in the procedural task 'Tower of Hanoi' of neuroleptic-naive schizophrenic patients. Author(s): Gimenez M, Junque C, Perez M, Vendrell P, Baeza I, Salamero M, Mercader JM, Bernardo M. Source: Neuroscience Letters. 2003 August 21; 347(2): 97-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12873737
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Basal ganglia network mediates the control of movement amplitude. Author(s): Desmurget M, Grafton ST, Vindras P, Grea H, Turner RS. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2003 November; 153(2): 197-209. Epub 2003 September 06. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680045
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Basal ganglia neuronal discharge in primary and secondary dystonia in patients undergoing pallidotomy. Author(s): Sanghera MK, Grossman RG, Kalhorn CG, Hamilton WJ, Ondo WG, Jankovic J. Source: Neurosurgery. 2003 June; 52(6): 1358-70; Discussion 1370-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12762881
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Basal ganglia neuronal discharge in primary and secondary dystonia. Author(s): Sanghera MK, Grossman RG, Kalhorn CG, Hamilton WJ, Ondo WG, Jankovic J. Source: Adv Neurol. 2004; 94: 29-36. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14509651
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Basal ganglia systems in ritualistic social displays: reptiles and humans; function and illness. Author(s): Baxter LR Jr. Source: Physiology & Behavior. 2003 August; 79(3): 451-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954439
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Basal Ganglia volumes in patients with Gilles de la Tourette syndrome. Author(s): Peterson BS, Thomas P, Kane MJ, Scahill L, Zhang H, Bronen R, King RA, Leckman JF, Staib L. Source: Archives of General Psychiatry. 2003 April; 60(4): 415-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12695320
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Basal ganglia: anatomy, pathology, and imaging characteristics. Author(s): Anderson JC, Costantino MM, Stratford T. Source: Current Problems in Diagnostic Radiology. 2004 January-February; 33(1): 28-41. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14712200
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Behavior and the basal ganglia. Author(s): Saint-Cyr JA, Taylor AE, Nicholson K. Source: Adv Neurol. 1995; 65: 1-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7872134
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Bilateral basal ganglia infarctions in a patient with Streptococcus pneumoniae meningitis. Author(s): Johkura K, Nishiyama T, Kuroiwa Y. Source: European Neurology. 2002; 48(2): 123-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12187007
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Bilateral lesions in the basal ganglia of a patient with acquired immunodeficiency syndrome. Author(s): Ueda A, Gatanaga H, Kikuchi Y, Hasuo K, Kimura S, Oka S. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 2003 October 1; 37(7): 943, 978-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521151
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Calcification of the basal ganglia in chronic hypoparathyroidism. Author(s): Rastogi R, Beauchamp NJ, Ladenson PW. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 1476-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12679425
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Cerebral blood flow in basal ganglia is correlated with clinical signs of hepatic encephalopathy in patients with liver cirrhosis. Author(s): Iwasa M, Kaito M, Adachi Y, Watanabe Y, Matsumura K, Takeda K. Source: The American Journal of Gastroenterology. 2002 March; 97(3): 763-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11922581
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Cerebral vasculitis as the only manifestation of Borrelia burgdorferi infection in a 17year-old patient with basal ganglia infarction. Author(s): Heinrich A, Khaw AV, Ahrens N, Kirsch M, Dressel A. Source: European Neurology. 2003; 50(2): 109-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12944718
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Chemical neuroanatomy of the basal ganglia--normal and in Parkinson's disease. Author(s): Hornykiewicz O. Source: Journal of Chemical Neuroanatomy. 2001 July; 22(1-2): 3-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11470551
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Childhood onset generalised dystonia can be modelled by increased gain in the indirect basal ganglia pathway. Author(s): Sanger TD. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 November; 74(11): 1509-15. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14617707
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Chorea associated with non-ketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI study: a meta-analysis of 53 cases including four present cases. Author(s): Oh SH, Lee KY, Im JH, Lee MS. Source: Journal of the Neurological Sciences. 2002 August 15; 200(1-2): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12127677
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Clinical significance of basal ganglia alterations at brain MRI and 1H MRS in cirrhosis and role in the pathogenesis of hepatic encephalopathy. Author(s): Spahr L, Burkhard PR, Grotzsch H, Hadengue A. Source: Metabolic Brain Disease. 2002 December; 17(4): 399-413. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602516
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Cognitive and behavioral changes in patients with focal lesions of the basal ganglia. Author(s): Dubois B, Defontaines B, Deweer B, Malapani C, Pillon B. Source: Adv Neurol. 1995; 65: 29-41. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7872147
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Cognitive and motor functioning in a patient with selective infarction of the left basal ganglia: evidence for decreased non-routine response selection and performance. Author(s): Troyer AK, Black SE, Armilio ML, Moscovitch M. Source: Neuropsychologia. 2004; 42(7): 902-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14998704
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Comparative cellular distribution of GABAA and GABAB receptors in the human basal ganglia: immunohistochemical colocalization of the alpha 1 subunit of the GABAA receptor, and the GABABR1 and GABABR2 receptor subunits. Author(s): Waldvogel HJ, Billinton A, White JH, Emson PC, Faull RL. Source: The Journal of Comparative Neurology. 2004 March 15; 470(4): 339-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14961561
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Comparison of the basal ganglia in rats, marmosets, macaques, baboons, and humans: volume and neuronal number for the output, internal relay, and striatal modulating nuclei. Author(s): Hardman CD, Henderson JM, Finkelstein DI, Horne MK, Paxinos G, Halliday GM. Source: The Journal of Comparative Neurology. 2002 April 8; 445(3): 238-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11920704
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Complementary roles of basal ganglia and cerebellum in learning and motor control. Author(s): Doya K. Source: Current Opinion in Neurobiology. 2000 December; 10(6): 732-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11240282
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Conditional ablation of striatal neuronal types containing dopamine D2 receptor disturbs coordination of basal ganglia function. Author(s): Sano H, Yasoshima Y, Matsushita N, Kaneko T, Kohno K, Pastan I, Kobayashi K. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 October 8; 23(27): 9078-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14534241
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Congenital fibrosis of the extraocular muscles associated with cortical dysplasia and maldevelopment of the basal ganglia. Author(s): Flaherty MP, Grattan-Smith P, Steinberg A, Jamieson R, Engle EC. Source: Ophthalmology. 2001 July; 108(7): 1313-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11425694
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Contributions of the prefrontal cortex and basal ganglia to set shifting. Author(s): Ravizza SM, Ciranni MA. Source: Journal of Cognitive Neuroscience. 2002 April 1; 14(3): 472-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11970806
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Cooperation of the basal ganglia, cerebellum, sensory cerebrum and hippocampus: possible implications for cognition, consciousness, intelligence and creativity. Author(s): Cotterill RM. Source: Progress in Neurobiology. 2001 May; 64(1): 1-33. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11250060
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Corticobasal degeneration syndrome with basal ganglia calcification: Fahr's disease as a corticobasal look-alike? Author(s): Lang AE. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 March; 18(3): 351-2; Author Reply 352. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12621646
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Corticobasal degeneration syndrome with basal ganglia calcification: Fahr's disease as a corticobasal look-alike? Author(s): Warren JD, Mummery CJ, Al-Din AS, Brown P, Wood NW. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002 May; 17(3): 563-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12112208
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Cysticercosis lesions in basal ganglia are common but clinically silent. Author(s): Cosentino C, Velez M, Torres L, Garcia HH; Cysticercosis Working Group in Peru. Source: Clinical Neurology and Neurosurgery. 2002 January; 104(1): 57-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11792479
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Deep arteriovenous malformations of the basal ganglia and thalamus: natural history. Author(s): Fleetwood IG, Marcellus ML, Levy RP, Marks MP, Steinberg GK. Source: Journal of Neurosurgery. 2003 April; 98(4): 747-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12691399
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Depression does not influence basal ganglia-mediated psychomotor speed in HIV-1 infection. Author(s): von Giesen HJ, Backer R, Hefter H, Arendt G. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2001 Winter; 13(1): 88-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11207334
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Development of the nigrostriatal dopamine neuron and the pathways in the basal ganglia. Author(s): Segawa M. Source: Brain & Development. 2000 September; 22 Suppl 1: S1-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984655
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Developmental and age-related changes of dopamine transporter, and dopamine D1 and D2 receptors in human basal ganglia. Author(s): Meng SZ, Ozawa Y, Itoh M, Takashima S. Source: Brain Research. 1999 October 2; 843(1-2): 136-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10528120
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Differential contributions of motor cortex, basal ganglia, and cerebellum to speech motor control: effects of syllable repetition rate evaluated by fMRI. Author(s): Wildgruber D, Ackermann H, Grodd W. Source: Neuroimage. 2001 January; 13(1): 101-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11133313
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Differential vulnerability of hippocampus, basal ganglia, and prefrontal cortex to long-term NMDA excitotoxicity. Author(s): Bernal F, Saura J, Ojuel J, Mahy N. Source: Experimental Neurology. 2000 February; 161(2): 686-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10686087
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Diffuse central nervous system lupus involving white matter, basal ganglia, thalami and brainstem. Author(s): Shibata M, Kibe T, Fujimoto S, Ishikawa T, Murakami M, Ichiki T, Wada Y. Source: Brain & Development. 1999 July; 21(5): 337-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10413022
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Disorders of the basal ganglia and their modern management. Author(s): Schrag A, Quinn N. Source: Journal of the Royal College of Physicians of London. 1999 July-August; 33(4): 323-7. Review. Erratum In: J R Coll Physicians Lond 1999 September-October; 33(5): 444. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10472019
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Dissociating hippocampal versus basal ganglia contributions to learning and transfer. Author(s): Myers CE, Shohamy D, Gluck MA, Grossman S, Kluger A, Ferris S, Golomb J, Schnirman G, Schwartz R. Source: Journal of Cognitive Neuroscience. 2003 February 15; 15(2): 185-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12676056
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Dissociating medial temporal and basal ganglia memory systems with a latent learning task. Author(s): Myers CE, Shohamy D, Gluck MA, Grossman S, Onlaor S, Kapur N. Source: Neuropsychologia. 2003; 41(14): 1919-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572525
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Distribution and modulation of histamine H(3) receptors in basal ganglia and frontal cortex of healthy controls and patients with Parkinson's disease. Author(s): Anichtchik OV, Peitsaro N, Rinne JO, Kalimo H, Panula P. Source: Neurobiology of Disease. 2001 August; 8(4): 707-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11493035
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Distribution and roles of metabotropic glutamate receptors in the basal ganglia motor circuit: implications for treatment of Parkinson's disease and related disorders. Author(s): Rouse ST, Marino MJ, Bradley SR, Awad H, Wittmann M, Conn PJ. Source: Pharmacology & Therapeutics. 2000 December; 88(3): 427-35. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11337032
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Distribution of basal ganglia lesions in diffuse neurofibrillary tangles with calcification: a clinicopathological study of five autopsy cases. Author(s): Tsuchiya K, Nakayama H, Iritani S, Arai T, Niizato K, Haga C, Matsushita M, Ikeda K. Source: Acta Neuropathologica. 2002 June; 103(6): 555-64. Epub 2002 February 01. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12012087
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Disturbances of learning processes in the basal ganglia in the pathogenesis of Parkinson's disease: a novel theory. Author(s): Baev KV. Source: Neurological Research. 1995 February; 17(1): 38-48. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7746342
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Does asymmetric basal ganglia or thalamic activation aid in seizure foci lateralization on ictal SPECT studies? Author(s): Sojkova J, Lewis PJ, Siegel AH, Siegel AM, Roberts DW, Thadani VM, Williamson PD; SPECT studies. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2003 September; 44(9): 1379-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12960180
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Does imbalance between basal ganglia and cerebellar outputs cause movement disorders? Author(s): Stein JF, Aziz TZ. Source: Current Opinion in Neurology. 1999 December; 12(6): 667-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10676745
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Dopamine D(1) receptor expression in human basal ganglia and changes in Parkinson's disease. Author(s): Hurley MJ, Mash DC, Jenner P. Source: Brain Research. Molecular Brain Research. 2001 March 5; 87(2): 271-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11245931
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Dopamine-dependent changes in the functional connectivity between basal ganglia and cerebral cortex in humans. Author(s): Williams D, Tijssen M, Van Bruggen G, Bosch A, Insola A, Di Lazzaro V, Mazzone P, Oliviero A, Quartarone A, Speelman H, Brown P. Source: Brain; a Journal of Neurology. 2002 July; 125(Pt 7): 1558-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12077005
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Dopaminergic innervation of human basal ganglia. Author(s): Prensa L, Cossette M, Parent A. Source: Journal of Chemical Neuroanatomy. 2000 December; 20(3-4): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11207419
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Dysfunction of the basal ganglia, but not the cerebellum, impairs kinaesthesia. Author(s): Maschke M, Gomez CM, Tuite PJ, Konczak J. Source: Brain; a Journal of Neurology. 2003 October; 126(Pt 10): 2312-22. Epub 2003 June 23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12821507
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Early prediction of aphasia outcome in left basal ganglia hemorrhage. Author(s): Liang CL, Chang HW, Lu K, Lee TC, Liliang PC, Lu CH, Chen HJ. Source: Acta Neurologica Scandinavica. 2001 March; 103(3): 148-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11240561
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Effect of basal ganglia injury on central dopamine activity in Gulf War syndrome: correlation of proton magnetic resonance spectroscopy and plasma homovanillic acid levels. Author(s): Haley RW, Fleckenstein JL, Marshall WW, McDonald GG, Kramer GL, Petty F. Source: Archives of Neurology. 2000 September; 57(9): 1280-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10987894
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Effects of left basal ganglia lesions on language production. Author(s): Fabbro F, Clarici A, Bava A. Source: Percept Mot Skills. 1996 June; 82(3 Pt 2): 1291-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8823893
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Effects of portal-systemic shunt embolization on the basal ganglia: MRI. Author(s): Matsumoto S, Mori H, Yoshioka K, Kiyosue H, Komatsu E. Source: Neuroradiology. 1997 May; 39(5): 326-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9189876
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Effects of systemic 3-nitropropionic acid-induced lesions of the dorsal striatum on cannabinoid and mu-opioid receptor binding in the basal ganglia. Author(s): Page KJ, Besret L, Jain M, Monaghan EM, Dunnett SB, Everitt BJ. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2000 January; 130(2): 142-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10672467
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Eighty-nine-year-old man with generalised chorea and basal ganglia mineralization. Author(s): Warren JD, Kimber TE, Blumbergs PC, Thompson PD. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2001 March; 16(2): 362-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11295798
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Electrical inhibition of basal ganglia nuclei in Parkinson's disease: long-term results. Author(s): Barcia-Salorio JL, Roldan P, Talamantes F, Pascual-Leone A. Source: Stereotactic and Functional Neurosurgery. 1999; 72(2-4): 202-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10853079
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Elevated basal ganglia glucose metabolism in cyclosporine neurotoxicity: a positron emission tomography imaging study. Author(s): Meyer MA. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2002 January; 12(1): 92-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826612
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Embolization of basal ganglia and thalamic arteriovenous malformations. Author(s): Paulsen RD, Steinberg GK, Norbash AM, Marcellus ML, Marks MP. Source: Neurosurgery. 1999 May; 44(5): 991-6; Discussion 996-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10232532
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Encephalitis lethargica syndrome: 20 new cases and evidence of basal ganglia autoimmunity. Author(s): Dale RC, Church AJ, Surtees RA, Lees AJ, Adcock JE, Harding B, Neville BG, Giovannoni G. Source: Brain; a Journal of Neurology. 2004 January; 127(Pt 1): 21-33. Epub 2003 October 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14570817
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Endocannabinoids and basal ganglia functionality. Author(s): Fernandez-Ruiz J, Lastres-Becker I, Cabranes A, Gonzalez S, Ramos JA. Source: Prostaglandins, Leukotrienes, and Essential Fatty Acids. 2002 February-March; 66(2-3): 257-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052041
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Epidemiological, genetic, pharmacological, kinesiological, nuclear medical (IBZMSPECT), standard and functional MRI studies on Parkinson's disease and related disorders and economic evaluation of Parkinson's disease therapy--clinical projects in the BMFT-research program Munich: "Parkinson's disease and other basal ganglia disorders". Author(s): Oertel WH, Trenkwalder C, Gasser T, Schwarz J, Bucher SF, Eichhorn T, Pogarell O, Kunig G, Arnold G, Bandmann O, et al. Source: Journal of Neural Transmission. Supplementum. 1995; 46: 325-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8821069
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Evidence for altered basal ganglia and cortical functions in transient idiopathic dystonia. Author(s): John B, Klemm E, Haverkamp F. Source: Journal of Child Neurology. 2000 December; 15(12): 820-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11198500
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Evolution of high-intensity basal ganglia lesions on T1-weighted MR in neurofibromatosis type 1. Author(s): Terada H, Barkovich AJ, Edwards MS, Ciricillo SM. Source: Ajnr. American Journal of Neuroradiology. 1996 April; 17(4): 755-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8730197
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Evolution of the basal ganglia: new perspectives through a comparative approach. Author(s): Smeets WJ, Marin O, Gonzalez A. Source: Journal of Anatomy. 2000 May; 196 ( Pt 4): 501-17. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923983
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Expression of 10 GABA(A) receptor subunit messenger RNAs in the motor-related thalamic nuclei and basal ganglia of Macaca mulatta studied with in situ hybridization histochemistry. Author(s): Kultas-Ilinsky K, Leontiev V, Whiting PJ. Source: Neuroscience. 1998 July; 85(1): 179-204. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9607711
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Expression of cannabinoid CB1 receptor mRNA in basal ganglia of normal and parkinsonian human brain. Author(s): Hurley MJ, Mash DC, Jenner P. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2003 November; 110(11): 1279-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628192
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Expression of glutamate receptors in the human and rat basal ganglia: effect of the dopaminergic denervation on AMPA receptor gene expression in the striatopallidal complex in Parkinson's disease and rat with 6-OHDA lesion. Author(s): Bernard V, Gardiol A, Faucheux B, Bloch B, Agid Y, Hirsch EC. Source: The Journal of Comparative Neurology. 1996 May 13; 368(4): 553-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8744443
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Extrapontine myelinolysis of the basal ganglia without central pontine myelinolysis. Author(s): Hadfield MG, Kubal WS. Source: Clin Neuropathol. 1996 March-April; 15(2): 96-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8925604
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Extrastriatal dopaminergic innervation of human basal ganglia. Author(s): Cossette M, Levesque M, Parent A. Source: Neuroscience Research. 1999 May; 34(1): 51-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10413327
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Familial idiopathic basal ganglia calcification (Fahr's disease) without neurological, cognitive and psychiatric symptoms is not linked to the IBGC1 locus on chromosome 14q. Author(s): Brodaty H, Mitchell P, Luscombe G, Kwok JJ, Badenhop RF, McKenzie R, Schofield PR. Source: Human Genetics. 2002 January; 110(1): 8-14. Epub 2001 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11810290
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Fatigue and basal ganglia. Author(s): Chaudhuri A, Behan PO. Source: Journal of the Neurological Sciences. 2000 October 1; 179(S 1-2): 34-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11054483
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Flow phenomena in a cystic basal ganglia structure do not rule out a lacunar infarct. Author(s): Moody DM, Challa VR, Mathews VP. Source: Ajnr. American Journal of Neuroradiology. 1995 January; 16(1): 217-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7900598
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Frequency of linear hyperechogenicity over the basal ganglia in young infants with congenital rubella syndrome. Author(s): Chang YC, Huang CC, Liu CC. Source: Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America. 1996 March; 22(3): 569-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8852982
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From experimentation to the surgical treatment of Parkinson's disease: prelude or suite in basal ganglia research? Author(s): Gross CE, Boraud T, Guehl D, Bioulac B, Bezard E. Source: Progress in Neurobiology. 1999 December; 59(5): 509-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10515666
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From single extracellular unit recording in experimental and human Parkinsonism to the development of a functional concept of the role played by the basal ganglia in motor control. Author(s): Boraud T, Bezard E, Bioulac B, Gross CE. Source: Progress in Neurobiology. 2002 March; 66(4): 265-83. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11960681
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Frontal N30 of median nerve SSEPs for evaluation of movement disorders with destructive basal ganglia deficits. Author(s): Fukuda C, Tomita Y, Maegaki Y, Kubota N. Source: Neuropediatrics. 2003 August; 34(4): 205-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12973662
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Function of the 'direct' and 'indirect' pathways of the basal ganglia motor loop: evidence from reciprocal aiming movements in Parkinson's disease. Author(s): Onla-or S, Winstein CJ. Source: Brain Research. Cognitive Brain Research. 2001 January; 10(3): 329-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11167056
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Functional anatomy of thalamus and basal ganglia. Author(s): Herrero MT, Barcia C, Navarro JM. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2002 August; 18(8): 386-404. Epub 2002 July 26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12192499
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Functional anatomy of the basal ganglia. Author(s): Yelnik J. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002; 17 Suppl 3: S15-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11948751
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Functional anatomy of the basal ganglia. Author(s): Aird T. Source: The Journal of Neuroscience Nursing : Journal of the American Association of Neuroscience Nurses. 2000 October; 32(5): 250-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11089195
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Functional and pathophysiological models of the basal ganglia. Author(s): Wichmann T, DeLong MR. Source: Current Opinion in Neurobiology. 1996 December; 6(6): 751-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9000030
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Functional and pathophysiological models of the basal ganglia: therapeutic implications. Author(s): DeLong MR. Source: Rinsho Shinkeigaku. 2000 December; 40(12): 1184. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11464452
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Functional changes of the basal ganglia circuitry in Parkinson's disease. Author(s): Blandini F, Nappi G, Tassorelli C, Martignoni E. Source: Progress in Neurobiology. 2000 September; 62(1): 63-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10821982
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Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry. Author(s): Teicher MH, Anderson CM, Polcari A, Glod CA, Maas LC, Renshaw PF. Source: Nature Medicine. 2000 April; 6(4): 470-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10742158
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Functional magnetic resonance imaging evidence for disrupted basal ganglia function in schizophrenia. Author(s): Menon V, Anagnoson RT, Glover GH, Pfefferbaum A. Source: The American Journal of Psychiatry. 2001 April; 158(4): 646-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11282705
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Functional magnetic resonance imaging of the basal ganglia and cerebellum using a simple motor paradigm. Author(s): Reichenbach JR, Feiwell R, Kuppusamy K, Bahn M, Haacke EM. Source: Magnetic Resonance Imaging. 1998 April; 16(3): 281-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9621969
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Functional MR imaging activation after finger tapping has a shorter duration in the basal ganglia than in the sensorimotor cortex. Author(s): Moritz CH, Meyerand ME, Cordes D, Haughton VM. Source: Ajnr. American Journal of Neuroradiology. 2000 August; 21(7): 1228-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10954273
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Functional neuroanatomy of the basal ganglia in Parkinson's disease. Author(s): Wichmann T, DeLong MR. Source: Adv Neurol. 2003; 91: 9-18. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12442660
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Functional organization of the circuits connecting the cerebral cortex and the basal ganglia: implications for the role of the basal ganglia in epilepsy. Author(s): Slaght SJ, Paz T, Mahon S, Maurice N, Charpier S, Deniau JM. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2002 December; 4 Suppl 3: S9-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495871
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Gait variability and basal ganglia disorders: stride-to-stride variations of gait cycle timing in Parkinson's disease and Huntington's disease. Author(s): Hausdorff JM, Cudkowicz ME, Firtion R, Wei JY, Goldberger AL. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1998 May; 13(3): 428-37. Erratum In: Mov Disord 1998 July; 13(4): 757. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9613733
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Gamma knife radiosurgery in the management of arteriovenous malformations of the Basal Ganglia region of the brain. Author(s): Nicolato A, Foroni R, Crocco A, Zampieri PG, Alessandrini F, Bricolo A, Gerosa MA. Source: Minimally Invasive Neurosurgery : Min. 2002 December; 45(4): 211-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12494356
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Ganglioglioma in the basal ganglia totally resected by a trans-distal Sylvian approach. Author(s): Fujimura M, Kayama T, Kumabe T, Yoshimoto T. Source: The Tohoku Journal of Experimental Medicine. 1995 March; 175(3): 211-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792790
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Generalised dystonia with an abnormal magnetic resonance imaging signal in the basal ganglia: a case of adult-onset GM1 gangliosidosis. Author(s): Campdelacreu J, Munoz E, Gomez B, Pujol T, Chabas A, Tolosa E. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002 September; 17(5): 1095-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12360569
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Generalized chorea due to basal ganglia lacunar infarcts. Author(s): Sethi KD, Nichols FT, Yaghmai F. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1987; 2(1): 61-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3504261
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Germ cell tumor arising in the basal ganglia in a female--case report. Author(s): Kobayashi H, Yamada H, Sakai N, Andoh T, Shinoda J. Source: Neurol Med Chir (Tokyo). 1990 February; 30(2): 123-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1695333
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Germ cell tumor in the basal ganglia: immunohistochemical demonstration of alphafetoprotein, human chorionic gonadotropin, and carcinoembryonic antigen. Author(s): Ono N, Inoue HK, Naganuma H, Misumi S, Tamura M. Source: Surgical Neurology. 1986 May; 25(5): 495-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2421426
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Germ cell tumors of the basal ganglia and thalamus. Author(s): Yasue M, Tanaka H, Nakajima M, Kamio M, Nakamura N, Numoto T, Tanaka J. Source: Pediatric Neurosurgery. 1993 May-June; 19(3): 121-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8499324
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Germ cell tumors of the thalamus and the basal ganglia. Author(s): Tamaki N, Lin T, Shirataki K, Hosoda K, Kurata H, Matsumoto S, Ito H. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1990 January; 6(1): 3-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2178773
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Germinoma arising in the basal ganglia in early stage: CT and MR findings. Author(s): Yamana D, Tohyama J, Mike T, Fukaya N, Okano M, Mimura M, Banno T, Ohba S. Source: Radiat Med. 1995 November-December; 13(6): 305-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8850373
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Germinoma of the basal ganglia and thalamus--CT and MRI findings. Author(s): Wong LW, Jayakumar CR. Source: Singapore Med J. 1997 October; 38(10): 444-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9529959
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Germinoma of the basal ganglia: a case report and review of literature. Author(s): Elizabeth J, Menon G, Bhattacharya RN, Radhakrishnan VV. Source: Neurology India. 2002 March; 50(1): 84-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11965648
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Germinoma originating in the basal ganglia and thalamus: MR and CT evaluation. Author(s): Higano S, Takahashi S, Ishii K, Matsumoto K, Ikeda H, Sakamoto K. Source: Ajnr. American Journal of Neuroradiology. 1994 September; 15(8): 1435-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7985560
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Germinoma originating in the basal ganglia. Report of a case showing unusual appearance on MRI. Author(s): Anno Y, Hori T, Watanabe T, Takenobu A, Takigawa H, Kishimoto M, Tanaka J. Source: Neuroradiology. 1990; 32(6): 529-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2287389
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Germinomas of the basal ganglia and thalamus: MR findings and a comparison between MR and CT. Author(s): Moon WK, Chang KH, Kim IO, Han MH, Choi CG, Suh DC, Yoo SJ, Han MC. Source: Ajr. American Journal of Roentgenology. 1994 June; 162(6): 1413-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8192009
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Glutamate decarboxylase-67 messenger RNA expression in normal human basal ganglia and in Parkinson's disease. Author(s): Nisbet AP, Eve DJ, Kingsbury AE, Daniel SE, Marsden CD, Lees AJ, Foster OJ. Source: Neuroscience. 1996 November; 75(2): 389-406. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8931005
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Glutamate/dopamine D1/D2 balance in the basal ganglia and its relevance to Parkinson's disease. Author(s): Starr MS. Source: Synapse (New York, N.Y.). 1995 April; 19(4): 264-93. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7792721
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Glutamate-dopamine interactions in the basal ganglia: relationship to Parkinson's disease. Author(s): Greenamyre JT. Source: Journal of Neural Transmission. General Section. 1993; 91(2-3): 255-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8099800
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Glutamatergic influences on the basal ganglia. Author(s): Greenamyre JT. Source: Clinical Neuropharmacology. 2001 March-April; 24(2): 65-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11307040
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G-proteins (Gi, Go) in the basal ganglia of control and schizophrenic brain. Author(s): Okada F, Crow TJ, Roberts GW. Source: Journal of Neural Transmission. General Section. 1990; 79(3): 227-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2105097
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Hemichorea and hemiballism associated with contralateral hemiparesis and ipsilateral basal ganglia lesions. Author(s): Krauss JK, Pohle T, Borremans JJ. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1999 May; 14(3): 497-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10348477
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Hemolytic uremic syndrome with particular involvement of basal ganglia and favorable outcome. Author(s): Barnett ND, Kaplan AM, Bernes SM, Cohen ML. Source: Pediatric Neurology. 1995 February; 12(2): 155-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7779215
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Hemolytic-uremic syndrome with involvement of basal ganglia and cerebellum. Author(s): Hager A, Staudt M, Klare B, von Einsiedel HG, Krageloh-Mann I. Source: Neuropediatrics. 1999 August; 30(4): 210-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10569213
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High frequency stimulation of the basal ganglia for the treatment of movement disorders: current status and clinical results. Author(s): Tronnier VM, Fogel W, Krause M, Bonsanto MM, Tronnier J, Heck A, Munkel K, Kunze S. Source: Minimally Invasive Neurosurgery : Min. 2002 June; 45(2): 91-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087506
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High levels of dopamine activity in the basal ganglia of cigarette smokers. Author(s): Salokangas RK, Vilkman H, Ilonen T, Taiminen T, Bergman J, Haaparanta M, Solin O, Alanen A, Syvalahti E, Hietala J. Source: The American Journal of Psychiatry. 2000 April; 157(4): 632-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10739427
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High uptake on 11C-methionine positron emission tomographic scan of basal ganglia germinoma with cerebral hemiatrophy. Author(s): Sudo A, Shiga T, Okajima M, Takano K, Terae S, Sawamura Y, Ohnishi A, Nagashima K, Saitoh S. Source: Ajnr. American Journal of Neuroradiology. 2003 October; 24(9): 1909-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561627
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High-intensity basal ganglia lesions on T1-weighted images in two toddlers with elevated blood manganese with portosystemic shunts. Author(s): Ihara K, Hijii T, Kuromaru R, Ariyoshi M, Kira R, Fukushige J, Hara T. Source: Neuroradiology. 1999 March; 41(3): 195-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10206166
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High-signal basal ganglia on T1-weighted images in a patient with Sydenham's chorea. Author(s): Ikuta N, Hirata M, Sasabe F, Negoro K, Morimatsu M. Source: Neuroradiology. 1998 October; 40(10): 659-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9833896
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HIV dementia and the basal ganglia. Author(s): Berger JR, Nath A. Source: Intervirology. 1997; 40(2-3): 122-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9450229
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HIV dementia: the role of the basal ganglia and dopaminergic systems. Author(s): Berger JR, Arendt G. Source: Journal of Psychopharmacology (Oxford, England). 2000; 14(3): 214-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11106299
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Human skeletal muscle calcium channel alpha1S is expressed in the basal ganglia: distinctive expression pattern among L-type Ca2+ channels. Author(s): Takahashi Y, Jeong SY, Ogata K, Goto J, Hashida H, Isahara K, Uchiyama Y, Kanazawa I. Source: Neuroscience Research. 2003 January; 45(1): 129-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12507731
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Hyperintense basal ganglia lesions on T1-weighted images in hereditary hemorrhagic telangiectasia with hepatic involvement. Author(s): Baba Y, Ohkubo K, Hamada K, Hokotate H, Nakajo M. Source: Journal of Computer Assisted Tomography. 1998 November-December; 22(6): 976-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9843242
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Hyperintense basal ganglia on T1-weighted magnetic resonance images following postoperative parenteral nutrition in a pancreatoduodenectomized patient. Author(s): Iwase K, Kondoh H, Higaki J, Tanaka Y, Yoshikawa M, Hori S, Osuga K, Kamiike W. Source: Digestive Surgery. 2000; 17(2): 190-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10781990
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Hyperintense basal ganglia on T1-weighted magnetic resonance images in a patient with common variable immunodeficiency associated with elevated serum manganese. Author(s): Siger-Zajdel M, Selmaj K. Source: Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging. 2002 January; 12(1): 84-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11826608
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Hyperintense basal ganglia on T1-weighted MR images in a patient with central nervous system lupus and chorea. Author(s): Kashihara K, Nakashima S, Kohira I, Shohmori T, Fujiwara Y, Kuroda S. Source: Ajnr. American Journal of Neuroradiology. 1998 February; 19(2): 284-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9504479
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Hyperintense basal ganglia on T1-weighted MR imaging. Author(s): Lai PH, Chen C, Liang HL, Pan HB. Source: Ajr. American Journal of Roentgenology. 1999 April; 172(4): 1109-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10587157
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Hypertensive basal ganglia hemorrhage: a prospective study comparing surgical and nonsurgical management. Author(s): Tan SH, Ng PY, Yeo TT, Wong SH, Ong PL, Venketasubramanian N. Source: Surgical Neurology. 2001 November; 56(5): 287-92; Discussion 292-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11749988
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Hypointensity in T2-weighted images of the basal ganglia in solvent-exposed patients with multiple sclerosis: clinical, MRI and CSF characteristics. Author(s): Landtblom AM, Thuomas KA, Sjodqvist L, Flodin U, Nyland FH, Soderfeldt B. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2003 April; 24(1): 2-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12754650
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Hypotensive hemorrhagic necrosis in basal ganglia and brainstem. Author(s): Opeskin K, Burke MP. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 2000 December; 21(4): 406-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11111807
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Hypothalamic digoxin related membrane Na+-K+ ATPase inhibition and familial basal ganglia calcification. Author(s): Kurup RK, Kurup PA. Source: Neuroscience Research. 2002 January; 42(1): 35-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11814607
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Ictal hyperperfusion of cerebellum and basal ganglia in temporal lobe epilepsy: SPECT subtraction with MRI coregistration. Author(s): Shin WC, Hong SB, Tae WS, Seo DW, Kim SE. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 2001 June; 42(6): 853-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11390547
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Identification of a locus on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Author(s): Geschwind DH, Loginov M, Stern JM. Source: American Journal of Human Genetics. 1999 September; 65(3): 764-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10441584
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Identification of target areas for deep brain stimulation in human basal ganglia substructures based on median nerve sensory evoked potential criteria. Author(s): Klostermann F, Vesper J, Curio G. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 August; 74(8): 1031-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12876229
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Imaging basal ganglia function. Author(s): Brooks DJ. Source: Journal of Anatomy. 2000 May; 196 ( Pt 4): 543-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10923986
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Incidence and clinical significance of echogenic vasculature in the basal ganglia of newborns. Author(s): Shefer-Kaufman N, Mimouni FB, Stavorovsky Z, Meyer JJ, Dollberg S. Source: American Journal of Perinatology. 1999; 16(6): 315-9. Erratum In: Am J Perinatol 1999; 16(8): 439, 317-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10586986
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Increased basal ganglia iron levels in Huntington disease. Author(s): Bartzokis G, Cummings J, Perlman S, Hance DB, Mintz J. Source: Archives of Neurology. 1999 May; 56(5): 569-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10328252
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Increased basal ganglia volumes in velo-cardio-facial syndrome (deletion 22q11.2). Author(s): Eliez S, Barnea-Goraly N, Schmitt JE, Liu Y, Reiss AL. Source: Biological Psychiatry. 2002 July 1; 52(1): 68-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12079732
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Increased blood flow in the basal ganglia when using cues to direct attention. Author(s): Koski L, Paus T, Hofle N, Petrides M. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 1999 November; 129(2): 241-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10591898
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Increased brain-derived neurotrophic factor-containing axons in the basal ganglia of patients with multiple system atrophy. Author(s): Kawamoto Y, Nakamura S, Akiguchi I, Kimura J. Source: Journal of Neuropathology and Experimental Neurology. 1999 July; 58(7): 76572. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411346
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Increased cannabinoid CB1 receptor binding and activation of GTP-binding proteins in the basal ganglia of patients with Parkinson's syndrome and of MPTP-treated marmosets. Author(s): Lastres-Becker I, Cebeira M, de Ceballos ML, Zeng BY, Jenner P, Ramos JA, Fernandez-Ruiz JJ. Source: The European Journal of Neuroscience. 2001 December; 14(11): 1827-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11860478
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Infantile spasms with basal ganglia MRI hypersignal may reveal mitochondrial disorder due to T8993G MT DNA mutation. Author(s): Desguerre I, Pinton F, Nabbout R, Moutard ML, N'Guyen S, Marsac C, Ponsot G, Dulac O. Source: Neuropediatrics. 2003 June; 34(5): 265-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14598233
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Information processing, dimensionality reduction and reinforcement learning in the basal ganglia. Author(s): Bar-Gad I, Morris G, Bergman H. Source: Progress in Neurobiology. 2003 December; 71(6): 439-73. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013228
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Inhibition of ongoing responses following frontal, nonfrontal, and basal ganglia lesions. Author(s): Rieger M, Gauggel S, Burmeister K. Source: Neuropsychology. 2003 April; 17(2): 272-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12803433
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Interactions between frontal cortex and basal ganglia in working memory: a computational model. Author(s): Frank MJ, Loughry B, O'Reilly RC. Source: Cognitive, Affective & Behavioral Neuroscience. 2001 June; 1(2): 137-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12467110
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Interictal and ictal EEG activity in the basal ganglia: an SEEG study in patients with temporal lobe epilepsy. Author(s): Rektor I, Kuba R, Brazdil M. Source: Epilepsia. 2002 March; 43(3): 253-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11906510
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Intracellular pH measurements of the whole head and the basal ganglia in chronic liver disease: a phosphorus-31 MR spectroscopy study. Author(s): Patel N, Forton DM, Coutts GA, Thomas HC, Taylor-Robinson SD. Source: Metabolic Brain Disease. 2000 September; 15(3): 223-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11206591
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Intraoperative direct subcortical stimulation for identification of the internal capsule, combined with an image-guided stereotactic system during surgery for basal ganglia lesions. Author(s): Duffau H. Source: Surgical Neurology. 2000 March; 53(3): 250-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10773257
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Involvement of basal ganglia transmitter systems in movement initiation. Author(s): Hauber W. Source: Progress in Neurobiology. 1998 December; 56(5): 507-40. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9775402
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Ionotropic and metabotropic GABA and glutamate receptors in primate basal ganglia. Author(s): Smith Y, Charara A, Paquet M, Kieval JZ, Pare JF, Hanson JE, Hubert GW, Kuwajima M, Levey AI. Source: Journal of Chemical Neuroanatomy. 2001 July; 22(1-2): 13-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11470552
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Iron in the basal ganglia in Parkinson's disease. An in vitro study using extended Xray absorption fine structure and cryo-electron microscopy. Author(s): Griffiths PD, Dobson BR, Jones GR, Clarke DT. Source: Brain; a Journal of Neurology. 1999 April; 122 ( Pt 4): 667-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10219780
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Juvenile nephronophthisis with calcification of basal ganglia and pancreatic insufficiency. Author(s): Raafat F, Morita M, Lau M, Taylor CM, White RH. Source: Archives of Pathology & Laboratory Medicine. 1988 June; 112(6): 630-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3377663
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Kainic acid and neurotransmitter interactions in the basal ganglia. Author(s): McGeer PL, McGeer EG, Innanen VT. Source: Adv Biochem Psychopharmacol. 1980; 24: 185-91. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6105774
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Karak syndrome: a novel degenerative disorder of the basal ganglia and cerebellum. Author(s): Mubaidin A, Roberts E, Hampshire D, Dehyyat M, Shurbaji A, Mubaidien M, Jamil A, Al-Din A, Kurdi A, Woods CG. Source: Journal of Medical Genetics. 2003 July; 40(7): 543-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843330
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Kearns-Sayre syndrome, hypoparathyroidism, and basal ganglia calcification. Author(s): Dewhurst AG, Hall D, Schwartz MS, McKeran RO. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1986 November; 49(11): 1323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3794742
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Kearns-Sayre syndrome. A case of the complete syndrome with encephalic leukodystrophy and calcification of basal ganglia. Author(s): Carboni P, Giacanelli M, Porro G, Sideri G, Paolella A. Source: Italian Journal of Neurological Sciences. 1981 August; 2(3): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7341548
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Kingella kingae meningitis with bilateral infarcts of the basal ganglia. Author(s): Walterspiel JN. Source: Infection. 1983 November-December; 11(6): 307-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6668069
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Lactate rise in the basal ganglia accompanying finger movements: a localized 1HMRS study. Author(s): Kuwabara T, Watanabe H, Tsuji S, Yuasa T. Source: Brain Research. 1995 January 30; 670(2): 326-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7743199
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Lactic acidemia, mitochondrial myopathy, and basal ganglia calcification. Author(s): Markesbery WR. Source: Neurology. 1979 July; 29(7): 1057-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=224342
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Large basal ganglia cyst in site of previously radiated glioma. Case report. Author(s): Wise BL. Source: Neurosurgery. 1977 November-December; 1(3): 284-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=615975
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Late onset familial dystonia: could mitochondrial deficits induce a diffuse lesioning process of the whole basal ganglia system? Author(s): Caparros-Lefebvre D, Destee A, Petit H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1997 August; 63(2): 196203. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9285458
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Laterality, somatotopy and reproducibility of the basal ganglia and motor cortex during motor tasks. Author(s): Scholz VH, Flaherty AW, Kraft E, Keltner JR, Kwong KK, Chen YI, Rosen BR, Jenkins BG. Source: Brain Research. 2000 October 6; 879(1-2): 204-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11011024
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Lateralized differences in iodine-123-IBZM uptake in the basal ganglia in asymmetric Parkinson's disease. Author(s): Knable MB, Jones DW, Coppola R, Hyde TM, Lee KS, Gorey J, Weinberger DR. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1995 July; 36(7): 1216-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7790947
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Learning and memory functions of the Basal Ganglia. Author(s): Packard MG, Knowlton BJ. Source: Annual Review of Neuroscience. 2002; 25: 563-93. Epub 2002 March 27. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12052921
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Left and right basal ganglia and frontal activity during language generation: contributions to lexical, semantic, and phonological processes. Author(s): Crosson B, Benefield H, Cato MA, Sadek JR, Moore AB, Wierenga CE, Gopinath K, Soltysik D, Bauer RM, Auerbach EJ, Gokcay D, Leonard CM, Briggs RW. Source: Journal of the International Neuropsychological Society : Jins. 2003 November; 9(7): 1061-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738287
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Lesch-Nyhan disease and the basal ganglia. Author(s): Visser JE, Bar PR, Jinnah HA. Source: Brain Research. Brain Research Reviews. 2000 April; 32(2-3): 449-75. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10760551
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Lesion of the basal ganglia and surgery for Parkinson disease. Author(s): Obeso JA, Rodriguez MC, Guridi J, Alvarez L, Alvarez E, Macias R, Juncos JL, DeLong M. Source: Archives of Neurology. 2001 July; 58(7): 1165-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11448310
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Linear hyperechogenicity within the basal ganglia and thalamus of preterm infants. Author(s): Chamnanvanakij S, Rogers CG, Luppino C, Broyles SR, Hickman J, Perlman JM. Source: Pediatric Neurology. 2000 August; 23(2): 129-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11020637
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Liver dysfunction and probable manganese accumulation in the brainstem and basal ganglia. Author(s): Saito H, Ejima A. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1995 June; 58(6): 760-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7608690
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Localization and physiological roles of metabotropic glutamate receptors in the direct and indirect pathways of the basal ganglia. Author(s): Marino MJ, Awad H, Poisik O, Wittmann M, Conn PJ. Source: Amino Acids. 2002; 23(1-3): 185-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12373536
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Longitudinal change in basal ganglia volume in patients with Huntington's disease. Author(s): Aylward EH, Li Q, Stine OC, Ranen N, Sherr M, Barta PE, Bylsma FW, Pearlson GD, Ross CA. Source: Neurology. 1997 February; 48(2): 394-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9040728
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Longitudinal changes of metabolites in frontal lobes after hemorrhagic stroke of basal ganglia: a proton magnetic resonance spectroscopy study. Author(s): Kobayashi M, Takayama H, Suga S, Mihara B. Source: Stroke; a Journal of Cerebral Circulation. 2001 October; 32(10): 2237-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588307
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Long-term effects of perinatal asphyxia on basal ganglia neurotransmitter systems studied with microdialysis in rat. Author(s): Loidl CF, Herrera-Marschitz M, Andersson K, You ZB, Goiny M, O'Connor WT, Silveira R, Rawal R, Bjelke B, Chen Y, et al. Source: Neuroscience Letters. 1994 July 4; 175(1-2): 9-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7970219
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Lower levels of nucleoside triphosphate in the basal ganglia of depressed subjects: a phosphorous-31 magnetic resonance spectroscopy study. Author(s): Moore CM, Christensen JD, Lafer B, Fava M, Renshaw PF. Source: The American Journal of Psychiatry. 1997 January; 154(1): 116-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8988971
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Low-grade glial tumors in basal ganglia and thalamus: natural history and biological reappraisal. Author(s): Franzini A, Leocata F, Cajola L, Servello D, Allegranza A, Broggi G. Source: Neurosurgery. 1994 November; 35(5): 817-20; Discussion 820-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7838328
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Lysis of basal ganglia haematoma with recombinant tissue plasminogen activator (rtPA) after stereotactic aspiration: initial results. Author(s): Lippitz BE, Mayfrank L, Spetzger U, Warnke JP, Bertalanffy H, Gilsbach JM. Source: Acta Neurochirurgica. 1994; 127(3-4): 157-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7942196
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Magnetic resonance imaging of the brain in glutaric acidemia type I: a review of the literature and a report of four new cases with attention to the basal ganglia and imaging technique. Author(s): Desai NK, Runge VM, Crisp DE, Crisp MB, Naul LG. Source: Investigative Radiology. 2003 August; 38(8): 489-96. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874515
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Membrane phospholipid abnormalities of basal ganglia in never-treated schizophrenia: a 31P magnetic resonance spectroscopy study. Author(s): Jayakumar PN, Gangadhar BN, Subbakrishna DK, Janakiramaiah N, Srinivas JS, Keshavan MS. Source: Biological Psychiatry. 2003 August 15; 54(4): 491-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12915294
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Metabolite alterations in basal ganglia associated with psychiatric symptoms of abstinent toluene users: a proton MRS study. Author(s): Takebayashi K, Sekine Y, Takei N, Minabe Y, Isoda H, Takeda H, Nishimura K, Nakamura K, Suzuki K, Iwata Y, Sakahara H, Mori N. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 May; 29(5): 1019-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15039764
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Mineralization of the basal ganglia: implications for neuropsychiatry, pathology and neuroimaging. Author(s): Casanova MF, Araque JM. Source: Psychiatry Research. 2003 November 1; 121(1): 59-87. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14572624
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Modulation of the basal ganglia by metabotropic glutamate receptors: potential for novel therapeutics. Author(s): Marino MJ, Conn JP. Source: Curr Drug Targets Cns Neurol Disord. 2002 June; 1(3): 239-50. Review. Erratum In: Curr Drug Target Cns Neurol Disord. 2002 August; 1(4): 449. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12769617
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Motor performance and anatomic magnetic resonance imaging (MRI) of the basal ganglia in autism. Author(s): Hardan AY, Kilpatrick M, Keshavan MS, Minshew NJ. Source: Journal of Child Neurology. 2003 May; 18(5): 317-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12822815
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MRI evidence for the involvement of basal ganglia in epileptic seizures: an hypothesis. Author(s): Dematteis M, Kahane P, Vercueil L, Depaulis A. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2003 September; 5(3): 161-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14684352
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Multiple target aspiration technique for subacute stereotactic aspiration of hematomas within the basal ganglia. Author(s): Marquardt G, Wolff R, Seifert V. Source: Surgical Neurology. 2003 July; 60(1): 8-13; Discussion 13-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12865001
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Multiregional 1H-MRSI of the hippocampus, thalamus, and basal ganglia in schizophrenia. Author(s): Ende G, Braus DF, Walter S, Weber-Fahr W, Henn FA. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 February; 253(1): 9-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12664307
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Muscarinic receptors in basal ganglia in dementia with Lewy bodies, Parkinson's disease and Alzheimer's disease. Author(s): Piggott MA, Owens J, O'Brien J, Colloby S, Fenwick J, Wyper D, Jaros E, Johnson M, Perry RH, Perry EK. Source: Journal of Chemical Neuroanatomy. 2003 March; 25(3): 161-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12706204
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Natural killer cell proliferation and circulating cytokines in patients with bilateral basal ganglia calcification. Author(s): Morishima T, Morita M, Kato T, Hoshino Y, Kimura H. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 September; 9(5): 521-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220385
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Neurobiology of basal ganglia circuits in Tourette syndrome: faulty inhibition of unwanted motor patterns? Author(s): Mink JW. Source: Adv Neurol. 2001; 85: 113-22. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530421
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Neurochemical organization of the human basal ganglia: anatomofunctional territories defined by the distributions of calcium-binding proteins and SMI-32. Author(s): Morel A, Loup F, Magnin M, Jeanmonod D. Source: The Journal of Comparative Neurology. 2002 January 28; 443(1): 86-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793349
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Neurokinin peptides and neurokinin receptors as potential therapeutic intervention targets of basal ganglia in the prevention and treatment of Parkinson's disease. Author(s): Chen LW, Yung KK, Chan YS. Source: Current Drug Targets. 2004 February; 5(2): 197-206. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15011953
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Neuropathological evaluation of the diencephalon, basal ganglia and upper brainstem in alobar holoprosencephaly. Author(s): Hayashi M, Araki S, Kumada S, Itoh M, Morimatsu Y, Matsuyama H. Source: Acta Neuropathologica. 2004 March; 107(3): 190-6. Epub 2003 December 18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14685895
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Neuropsychiatry of the basal ganglia. Author(s): Ring HA, Serra-Mestres J. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 January; 72(1): 12-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11784818
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Neuropsychological correlates of basal ganglia and medial temporal lobe NAA/Cho reductions in traumatic brain injury. Author(s): Ariza M, Junque C, Mataro M, Poca MA, Bargallo N, Olondo M, Sahuquillo J. Source: Archives of Neurology. 2004 April; 61(4): 541-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15096403
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New syndrome characterized by hypomyelination with atrophy of the basal ganglia and cerebellum. Author(s): van der Knaap MS, Naidu S, Pouwels PJ, Bonavita S, van Coster R, Lagae L, Sperner J, Surtees R, Schiffmann R, Valk J. Source: Ajnr. American Journal of Neuroradiology. 2002 October; 23(9): 1466-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12372733
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Normal functional imaging of the basal ganglia. Author(s): Lehericy S, Gerardin E. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2002 December; 4 Suppl 3: S23-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495872
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Normal prism adaptation but reduced after-effect in basal ganglia disorders using a throwing task. Author(s): Fernandez-Ruiz J, Diaz R, Hall-Haro C, Vergara P, Mischner J, Nunez L, Drucker-Colin R, Ochoa A, Alonso ME. Source: The European Journal of Neuroscience. 2003 August; 18(3): 689-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911765
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Obsessive-compulsive and other behavioural changes with bilateral basal ganglia lesions. A neuropsychological, magnetic resonance imaging and positron tomography study. Author(s): Laplane D, Levasseur M, Pillon B, Dubois B, Baulac M, Mazoyer B, Tran Dinh S, Sette G, Danze F, Baron JC. Source: Brain; a Journal of Neurology. 1989 June; 112 ( Pt 3): 699-725. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2786440
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Obsessive-compulsive disorder, Tourette's syndrome, and basal ganglia pathology on MRI. Author(s): Saba PR, Dastur K, Keshavan MS, Katerji MA. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1998 Winter; 10(1): 116-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9547480
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Olfactory dysfunction in hereditary ataxia and basal ganglia disorders. Author(s): Fernandez-Ruiz J, Diaz R, Hall-Haro C, Vergara P, Fiorentini A, Nunez L, Drucker-Colin R, Ochoa A, Yescas P, Rasmussen A, Alonso ME. Source: Neuroreport. 2003 July 18; 14(10): 1339-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12876469
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On the role of the cerebellum and basal ganglia in cognitive signal processing. Author(s): Houk JC. Source: Prog Brain Res. 1997; 114: 543-52. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9193165
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Open interconnected model of basal ganglia-thalamocortical circuitry and its relevance to the clinical syndrome of Huntington's disease. Author(s): Joel D. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2001 May; 16(3): 407-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11391734
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Organization of the basal ganglia: the importance of axonal collateralization. Author(s): Parent A, Sato F, Wu Y, Gauthier J, Levesque M, Parent M. Source: Trends in Neurosciences. 2000 October; 23(10 Suppl): S20-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11052216
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Oscillations in the basal ganglia. Author(s): Wichmann T, DeLong MR. Source: Nature. 1999 August 12; 400(6745): 621-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10458157
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Oscillatory activity in the basal ganglia--relationship to normal physiology and pathophysiology. Author(s): Dostrovsky J, Bergman H. Source: Brain; a Journal of Neurology. 2004 April; 127(Pt 4): 721-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15044311
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Oscillatory nature of human basal ganglia activity: relationship to the pathophysiology of Parkinson's disease. Author(s): Brown P. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 April; 18(4): 357-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671940
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Oxidative damage and metabolic dysfunction in Huntington's disease: selective vulnerability of the basal ganglia. Author(s): Browne SE, Bowling AC, MacGarvey U, Baik MJ, Berger SC, Muqit MM, Bird ED, Beal MF. Source: Annals of Neurology. 1997 May; 41(5): 646-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9153527
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Parkinsonian rigidity, dopa-induced dyskinesia and chorea--dynamic studies on the basal ganglia-thalamocortical motor circuit using PET scan and depth microrecording. Author(s): Hirato M, Ishihara J, Horikoshi S, Shibazaki T, Ohye C. Source: Acta Neurochir Suppl (Wien). 1995; 64: 5-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8748574
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Parkinsonism and rest tremor secondary to supratentorial tumours sparing the basal ganglia. Author(s): Krauss JK, Paduch T, Mundinger F, Seeger W. Source: Acta Neurochirurgica. 1995; 133(1-2): 22-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8561031
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Perfusion-weighted dynamic susceptibility (DSC) MRI: basal ganglia hemodynamic changes after apomorphine in Parkinson's disease. Author(s): Brusa L, Bassi A, Pierantozzi M, Gaudiello S Frasca F, Floris R, Stanzione P. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2002 September; 23 Suppl 2: S61-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548344
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PET imaging in epilepsy: basal ganglia and thalamic involvement. Author(s): Semah F. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2002 December; 4 Suppl 3: S55-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495875
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Possible basal ganglia pathology in children with complex symptoms. Author(s): Yaryura-Tobias JA, Rabinowitz DC, Neziroglu F. Source: The Journal of Clinical Psychiatry. 2003 December; 64(12): 1495-501. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14728112
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Possible role of intramembrane receptor-receptor interactions in memory and learning via formation of long-lived heteromeric complexes: focus on motor learning in the basal ganglia. Author(s): Agnati LF, Franzen O, Ferre S, Leo G, Franco R, Fuxe K. Source: Journal of Neural Transmission. Supplementum. 2003; (65): 1-28. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946046
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Processing emotional tone from speech in Parkinson's disease: a role for the basal ganglia. Author(s): Pell MD, Leonard CL. Source: Cognitive, Affective & Behavioral Neuroscience. 2003 December; 3(4): 275-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15040548
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Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Author(s): Chaudhuri A, Condon BR, Gow JW, Brennan D, Hadley DM. Source: Neuroreport. 2003 February 10; 14(2): 225-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598734
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Proton MR spectroscopy of basal ganglia in Wilson's disease: case report and review of literature. Author(s): Jayasundar R, Sahani AK, Gaikwad S, Singh S, Behari M. Source: Magnetic Resonance Imaging. 2002 January; 20(1): 131-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11973039
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Quantitative evaluation of thalami and basal ganglia in infants with periventricular leukomalacia. Author(s): Lin Y, Okumura A, Hayakawa F, Kato K, Kuno T, Watanabe K. Source: Developmental Medicine and Child Neurology. 2001 July; 43(7): 481-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11463180
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Quantitative proton magnetic resonance spectroscopy of the basal ganglia in patients with affective disorders. Author(s): Hamakawa H, Kato T, Murashita J, Kato N. Source: European Archives of Psychiatry and Clinical Neuroscience. 1998; 248(1): 53-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9561353
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Radiosurgery for arteriovenous malformations of the basal ganglia, thalamus, and brainstem. Author(s): Pollock BE, Gorman DA, Brown PD. Source: Journal of Neurosurgery. 2004 February; 100(2): 210-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15086226
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Reappraisal of the motor role of basal ganglia: a functional magnetic resonance image study. Author(s): Taniwaki T, Okayama A, Yoshiura T, Nakamura Y, Goto Y, Kira J, Tobimatsu S. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 April 15; 23(8): 3432-8. Erratum In: J Neurosci. 2003 August 27; 23(21): 7966. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716951
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Reduced basal ganglia blood flow and volume in pre-symptomatic, gene-tested persons at-risk for Huntington's disease. Author(s): Harris GJ, Codori AM, Lewis RF, Schmidt E, Bedi A, Brandt J. Source: Brain; a Journal of Neurology. 1999 September; 122 ( Pt 9): 1667-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468506
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Reduced intracellular pH in the basal ganglia and whole brain measured by 31P-MRS in bipolar disorder. Author(s): Hamakawa H, Murashita J, Yamada N, Inubushi T, Kato N, Kato T. Source: Psychiatry and Clinical Neurosciences. 2004 February; 58(1): 82-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678462
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Regional and cellular localisation of GABA(A) receptor subunits in the human basal ganglia: An autoradiographic and immunohistochemical study. Author(s): Waldvogel HJ, Kubota Y, Fritschy J, Mohler H, Faull RL. Source: The Journal of Comparative Neurology. 1999 December 20; 415(3): 313-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10553118
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Relation between brain tissue pO2 and dopamine synthesis of basal ganglia--a 18FDOPA-PET study in newborn piglets. Author(s): Bauer R, Brust P, Walter B, Vorwieger G, Bergmann R, Fuchtner F, Steinbach J, el-Hallag E, Fritz A, Johannsen B, Zwiener U. Source: Journal of Perinatal Medicine. 2000; 28(1): 54-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10765515
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Relationship between obsessive-compulsive disorders and diseases affecting primarily the basal ganglia. Author(s): Maia AS, Barbosa ER, Menezes PR, Miguel Filho EC. Source: Revista Do Hospital Das Clinicas. 1999 November-December; 54(6): 213-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10881070
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Relationship between oscillations in the basal ganglia and synchronization of cortical activity. Author(s): Cassim F, Labyt E, Devos D, Defebvre L, Destee A, Derambure P. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2002 December; 4 Suppl 3: S31-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495873
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Reversible hyperintense T2 MRI lesions of basal ganglia after an electrical injury. Author(s): Sahiner T, Kurt T, Bir LS, Oguzhanoglu A, Akalin O, Celiker A, Ozdemir F. Source: Burns : Journal of the International Society for Burn Injuries. 2002 September; 28(6): 607-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220922
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Role of basal ganglia-brainstem systems in the control of postural muscle tone and locomotion. Author(s): Takakusaki K, Oohinata-Sugimoto J, Saitoh K, Habaguchi T. Source: Prog Brain Res. 2004; 143: 231-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14653168
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Seizures and the basal ganglia: a review of the clinical data. Author(s): Vercueil L, Hirsch E. Source: Epileptic Disorders : International Epilepsy Journal with Videotape. 2002 December; 4 Suppl 3: S47-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495874
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Self-organization in the basal ganglia with modulation of reinforcement signals. Author(s): Nakahara H, Amari Si S, Hikosaka O. Source: Neural Computation. 2002 April; 14(4): 819-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11936963
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Severe bruxism following basal ganglia infarcts: insights into pathophysiology. Author(s): Tan EK, Chan LL, Chang HM. Source: Journal of the Neurological Sciences. 2004 February 15; 217(2): 229-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706229
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Short-term administration of an essential trace elements preparation (Elemenmic) causes a high whole blood manganese concentration and manganese deposition in basal ganglia. Author(s): Orimo S, Ozawa E. Source: Intern Med. 2001 November; 40(11): 1162-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11757777
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Silent cerebral infarcts in basal ganglia are advanced in congenital protein C-deficient heterozygotes with hypertension. Author(s): Kario K, Sakata T, Higashikawa M, Katayama Y, Hoshide S, Shimada K, Miyata T. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 August; 14(8 Pt 1): 818-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11497200
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Stereotactic interstitial radiosurgery with a miniature X-ray device in the minimally invasive treatment of selected tumors in the thalamus and the basal Ganglia. Author(s): Gallina P, Francescon P, Cavedon C, Casamassima F, Mungai R, Perrini P, Russo S, Di Lorenzo N. Source: Stereotactic and Functional Neurosurgery. 2002; 79(3-4): 202-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890978
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Subacute stereotactic aspiration of haematomas within the basal ganglia reduces occurrence of complications in the course of haemorrhagic stroke in non-comatose patients. Author(s): Marquardt G, Wolff R, Sager A, Janzen RW, Seifert V. Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 15(4): 252-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12686788
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Subthalamic-pallidal interactions are critical in determining normal and abnormal functioning of the basal ganglia. Author(s): Gillies A, Willshaw D, Li Z. Source: Proceedings of the Royal Society of London. Series B. Biological Sciences. 2002 March 22; 269(1491): 545-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11916469
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Synchronized neuronal discharge in the basal ganglia of parkinsonian patients is limited to oscillatory activity. Author(s): Levy R, Hutchison WD, Lozano AM, Dostrovsky JO. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2002 April 1; 22(7): 2855-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11923450
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Syntactic language processing: ERP lesion data on the role of the basal ganglia. Author(s): Kotz SA, Frisch S, von Cramon DY, Friederici AD. Source: Journal of the International Neuropsychological Society : Jins. 2003 November; 9(7): 1053-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738286
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The anatomy of the basal ganglia and Parkinson's disease: a review. Author(s): Lee TK, Chau R, Leong SK. Source: Singapore Med J. 1995 February; 36(1): 74-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7570141
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The basal ganglia and inhibitory mechanisms in response selection: evidence from subliminal priming of motor responses in Parkinson's disease. Author(s): Seiss E, Praamstra P. Source: Brain; a Journal of Neurology. 2004 February; 127(Pt 2): 330-9. Epub 2003 November 25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14645146
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The Basal Ganglia and involuntary movements: impaired inhibition of competing motor patterns. Author(s): Mink JW. Source: Archives of Neurology. 2003 October; 60(10): 1365-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568805
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The basal ganglia and motor control. Author(s): Groenewegen HJ. Source: Neural Plast. 2003; 10(1-2): 107-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14640312
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The basal ganglia. Author(s): Graybiel AM. Source: Trends in Neurosciences. 1995 February; 18(2): 60-2. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7537409
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The functional anatomy of disorders of the basal ganglia. Author(s): Albin RL, Young AB, Penney JB. Source: Trends in Neurosciences. 1995 February; 18(2): 63-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7537410
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The origin of motor fluctuations in Parkinson's disease: importance of dopaminergic innervation and basal ganglia circuits. Author(s): Obeso JA, Rodriguez-Oroz M, Marin C, Alonso F, Zamarbide I, Lanciego JL, Rodriguez-Diaz M. Source: Neurology. 2004 January 13; 62(1 Suppl 1): S17-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14718677
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The primate basal ganglia: parallel and integrative networks. Author(s): Haber SN. Source: Journal of Chemical Neuroanatomy. 2003 December; 26(4): 317-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14729134
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The thalamus and basal ganglia: What is exactly where? A reply to 'Neuropsychological consequences of right thalamic injury: case study and review,' MJ Summers, Brain and Cognition 50 (2002). Author(s): Benke T. Source: Brain and Cognition. 2003 December; 53(3): 472-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14642297
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Ultrasonographic findings in thalamus and basal ganglia in term asphyxiated infants. Author(s): Cabanas F, Pellicer A, Perez-Higueras A, Garcia-Alix A, Roche C, Quero J. Source: Pediatric Neurology. 1991 May-June; 7(3): 211-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1878102
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Ultrastructural localization of immunoreactive calbindin-D28k in the rat and monkey basal ganglia, including subcellular distribution with colloidal gold labeling. Author(s): DiFiglia M, Christakos S, Aronin N. Source: The Journal of Comparative Neurology. 1989 January 22; 279(4): 653-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2918090
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Unchanged basal ganglia N-acetylaspartate and glutamate in idiopathic Parkinson's disease measured by proton magnetic resonance spectroscopy. Author(s): Clarke CE, Lowry M, Horsman A. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 1997 May; 12(3): 297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9159722
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Unilateral absence of the basal ganglia plus epilepsy without motor symptoms. Author(s): Kellinghaus C, Montgomery E, Neme S, Ruggieri P, Luders HO. Source: Neurology. 2003 March 11; 60(5): 870-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12629251
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Unilateral basal ganglia involvement in primary progressive aphasia. Author(s): Miwa H, Sato S, Mori H, Mizuno Y. Source: Journal of Neurology. 1995 May; 242(5): 350-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7543938
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Unilateral cerebral cortical and basal ganglia enhancement following overdosage of nonionic contrast media. Author(s): Kuhn MJ, Burk TJ, Powell FC. Source: Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. 1995 May-June; 19(3): 307-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7641175
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Unilateral globus pallidus internus stimulation improves delayed onset posttraumatic cervical dystonia with an ipsilateral focal basal ganglia lesion. Author(s): Chang JW, Choi JY, Lee BW, Kang UJ, Chung SS. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 November; 73(5): 588-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12397158
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Unsuccessful treatment with levodopa of a parkinsonian patient with calcification of the basal ganglia. Author(s): Berendes K, Dorstelmann D. Source: Journal of Neurology. 1978 April 14; 218(1): 51-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=77318
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Unusual roentgenological findings in cytomegalic inclusion body disease: large and circumscribed calcareous deposits of the basal ganglia and scattered calcifications of the parieto-occipital cortex. Author(s): Voigt K, Sauer M, Luthardt T. Source: Pediatric Radiology. 1975 January 24; 3(1): 47-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=184419
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Unusual signs for dural arteriovenous fistulas with diffuse basal ganglia and cerebral calcification. Author(s): Lai PH, Chang MH, Liang HL, Pan HB, Yang CF. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 April; 63(4): 329-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10820913
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Value of ultrasound for identification of acute hemorrhagic necrosis of thalamus and basal ganglia in an asphyxiated term infant. Author(s): Kreusser KL, Schmidt RE, Shackelford GD, Volpe JJ. Source: Annals of Neurology. 1984 September; 16(3): 361-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6486741
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Variation in echogenicity of the basal ganglia: anisotropic effect. Author(s): Ashraf VS, Feldstein VA, Filly RA. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 1999 February; 18(2): 153-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10206809
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Ventricular somatostatin-like immunoreactivity in patients with basal ganglia disease. Author(s): Cramer H, Wolf A, Rissler K, Weigel K, Ostertag C. Source: Journal of Neurology. 1985; 232(4): 219-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2864402
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Visual attentional disturbance with unilateral lesions in the basal ganglia and deep white matter. Author(s): Sakashita Y. Source: Annals of Neurology. 1991 November; 30(5): 673-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1763892
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Visualization of basal ganglia calification by cranial computed tomography in a patient with pseudohypoparathyroidism. Author(s): Korn-Lubetzki I, Rubinger D, Siew F. Source: Isr J Med Sci. 1980 January; 16(1): 40-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7358513
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Volumetric MRI changes in basal ganglia of children with Tourette's syndrome. Author(s): Singer HS, Reiss AL, Brown JE, Aylward EH, Shih B, Chee E, Harris EL, Reader MJ, Chase GA, Bryan RN, et al. Source: Neurology. 1993 May; 43(5): 950-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8492951
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Waisman syndrome, a human X-linked recessive basal ganglia disorder with mental retardation: localization to Xq27.3-qter. Author(s): Gregg RG, Metzenberg AB, Hogan K, Sekhon G, Laxova R. Source: Genomics. 1991 April; 9(4): 701-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1674730
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What do the basal ganglia do? Author(s): Brown P, Marsden CD. Source: Lancet. 1998 June 13; 351(9118): 1801-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635969
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What do the basal ganglia tell premotor cortical areas? Author(s): Marsden CD. Source: Ciba Found Symp. 1987; 132: 282-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2962840
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What is the psychiatric significance of bilateral basal ganglia mineralization? Author(s): Forstl H, Krumm B, Eden S, Kohlmeyer K. Source: Biological Psychiatry. 1991 April 15; 29(8): 827-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2054455
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Which motor disorder in Parkinson's disease indicates the true motor function of the basal ganglia? Author(s): Marsden CD. Source: Ciba Found Symp. 1984; 107: 225-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6568150
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Why the P600 is not just a P300: the role of the basal ganglia. Author(s): Frisch S, Kotz SA, von Cramon DY, Friederici AD. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 February; 114(2): 336-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12559242
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Wilson's disease: MRI demonstration of cavitations in basal ganglia and thalami. Author(s): Sener RN. Source: Pediatric Radiology. 1993; 23(2): 157. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8516046
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Zygomycosis of the basal ganglia in intravenous drug users. Author(s): Stave GM, Heimberger T, Kerkering TM. Source: The American Journal of Medicine. 1989 January; 86(1): 115-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2642654
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CHAPTER 2. NUTRITION AND BASAL GANGLIA Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and basal ganglia.
Finding Nutrition Studies on Basal Ganglia 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 “basal ganglia” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
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Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “basal ganglia” (or a synonym): •
1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative analysis. Author(s): Department of Diagnostic Radiology and Organ Imaging, Prince of Wales Hospital Shatin, N.T., Chinese University of Hong Kong, China. Source: Lam, W W Wang, Z J Zhao, H Berry, G T Kaplan, P Gibson, J Kaplan, B S Bilaniuk, L T Hunter, J V Haselgrove, J C Zimmermann, R A Neuroradiology. 1998 May; 40(5): 315-23 0028-3940
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Biotin-responsive basal ganglia disease: a novel entity. Author(s): Department of Paediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
[email protected] Source: Ozand, P T Gascon, G G Al Essa, M Joshi, S Al Jishi, E Bakheet, S Al Watban, J Al Kawi, M Z Dabbagh, O Brain. 1998 July; 121 ( Pt 7)1267-79 0006-8950
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Changes in endocannabinoid transmission in the basal ganglia in a rat model of Huntington's disease. Author(s): Departamento de Bioquimica y Biologia Molecular, Facultad de Medicina, Universidad Complutense, 28040-Madrid, Spain. Source: Lastres Becker, I Fezza, F Cebeira, M Bisogno, T Ramos, J A Milone, A Fernandez Ruiz, J Marzo, V D Neuroreport. 2001 July 20; 12(10): 2125-9 0959-4965
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Chronic D1 and D2 dopaminomimetic treatment of MPTP-denervated monkeys: effects on basal ganglia GABA(A)/benzodiazepine receptor complex and GABA content. Author(s): Centre de Recherches en Endocrinologie Moleculaire, Le Centre Hospitalier Universitaire de Quebec, Pavillon CHUL, Canada. Source: Calon, F Morissette, M Goulet, M Grondin, R Blanchet, P J Bedard, P J Di Paolo, T Neurochem-Int. 1999 July; 35(1): 81-91 0197-0186
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Distribution of dopamine transporters in basal ganglia of cerebellar ataxic mice by [125I]RTI-121 quantitative autoradiography. Author(s): Departement de Physiologie, Faculte de Medecine, Universite de Montreal, Quebec, Canada. Source: Strazielle, C Lalonde, R Amdiss, F Botez, M I Hebert, C Reader, T A NeurochemInt. 1998 January; 32(1): 61-8 0197-0186
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Dopamine agonist-mediated rotation in rats with unilateral nigrostriatal lesions is not dependent on net inhibitions of rate in basal ganglia output nuclei. Author(s): Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA. Source: Ruskin, D N Bergstrom, D A Mastropietro, C W Twery, M J Walters, J R Neuroscience. 1999; 91(3): 935-46 0306-4522
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Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist-stimulated [35S]guanylyl-5'O-(thio)-triphosphate binding in the basal ganglia of aged rats. Author(s): Instituto Complutense de Drogodependencias, Department of Biochemistry, Faculty of Medicine, Complutense University, Madrid, Spain. Source: Romero, J Berrendero, F Garcia Gil, L de la Cruz, P Ramos, J A Fernandez Ruiz, J J Neuroscience. 1998 June; 84(4): 1075-83 0306-4522
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Movement-related modulation of neural activity in human basal ganglia and its LDOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease. Author(s): Department of Neurological Sciences, IRCCS Ospedale Maggiore, Policlinico, University of Milan, Padiglione Ponti, Via F. Sforza 35, 20122 Milan, Italy. Source: Priori, A Foffani, G Pesenti, A Bianchi, A Chiesa, V Baselli, G Caputo, E Tamma, F Rampini, P Egidi, M Locatelli, M Barbieri, S Scarlato, G Neurol-Sci. 2002 September; 23 Suppl 2: S101-2 1590-1874
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Organization of inputs from cingulate motor areas to basal ganglia in macaque monkey. Author(s): Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan.
[email protected] Source: Takada, M Tokuno, H Hamada, I Inase, M Ito, Y Imanishi, M Hasegawa, N Akazawa, T Hatanaka, N Nambu, A Eur-J-Neurosci. 2001 November; 14(10): 1633-50 0953-816X
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Pharmacological MRI mapping of age-associated changes in basal ganglia circuitry of awake rhesus monkeys. Author(s): Department of Anatomy & Neurobiology, University of Kentucky, Lexington, Kentucky 40536, USA. Source: Zhang, Z Andersen, A Grondin, R Barber, T Avison, R Gerhardt, G Gash, D Neuroimage. 2001 November; 14(5): 1159-67 1053-8119
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Proton magnetic resonance spectroscopy (1H-MRS) of motor cortex and basal ganglia in de novo Parkinson's disease patients. Author(s): Department of Neuroscience, University of Pisa, Italy. Source: Lucetti, C Del Dotto, P Gambaccini, G Bernardini, S Bianchi, M C Tosetti, M Bonuccelli, U Neurol-Sci. 2001 February; 22(1): 69-70 1590-1874
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Respiratory responses to electrical stimulation of the basal ganglia in cats. Author(s): Institute of Human Movement Sciences, Faculty of Medicine, University of Pecs, Hungary. Source: Angyan, L Angyan, Z Neurobiology-(Bp). 2001; 9(2): 73-9 1216-8068
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The topography, structure and incidence of mineralized bodies in the basal ganglia of the brain of cynomolgus monkeys, (Macaca fascicularis). Source: Wadsworth, P.F. Jones, H.B. Cavanagh, J.B. Lab-anim. London : Royal Society of Medicine Press Ltd. July 1995. volume 29 (3) page 276-281. 0023-6772
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 basal ganglia; 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 Iron Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. GANGLIA
ALTERNATIVE MEDICINE AND BASAL
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to basal ganglia. 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 basal ganglia 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 “basal ganglia” (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 basal ganglia: •
1-methyl-1,2,3,4-tetrahydroisoquinoline protects against rotenone-induced mortality and biochemical changes in rat brain. Author(s): Antkiewicz-Michaluk L, Karolewicz B, Romanska I, Michaluk J, Bojarski AJ, Vetulani J. Source: European Journal of Pharmacology. 2003 April 18; 466(3): 263-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12694809
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99Tc(m)-ECD SPET perfusion changes by internal pallidum stimulation in Parkinson's disease. Author(s): van Laere K, van der Linden C, Santens P, Vandewalle V, Caemaert J, Ir PL, van den Abbeele D, Dierckx R. Source: Nuclear Medicine Communications. 2000 December; 21(12): 1103-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11200014
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A coil design for transcranial magnetic stimulation of deep brain regions. Author(s): Roth Y, Zangen A, Hallett M. Source: Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society. 2002 August; 19(4): 361-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12436090
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A differential involvement of the shell and core subterritories of the nucleus accumbens of rats in attentional processes. Author(s): Jongen-Relo AL, Kaufmann S, Feldon J. Source: Neuroscience. 2002; 111(1): 95-109. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11955715
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A double dissociation between serial reaction time and radial maze performance in rats subjected to 192 IgG-saporin lesions of the nucleus basalis and/or the septal region. Author(s): Lehmann O, Grottick AJ, Cassel JC, Higgins GA. Source: The European Journal of Neuroscience. 2003 August; 18(3): 651-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12911761
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A functional role for dopamine transmission in the amygdala during conditioned fear. Author(s): Guarraci FA, Frohardt RJ, Young SL, Kapp BS. Source: Annals of the New York Academy of Sciences. 1999 June 29; 877: 732-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10415694
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A gelatin in situ-overlay technique localizes brain matrix metalloproteinase activity in experimental focal cerebral ischemia. Author(s): Loy M, Burggraf D, Martens KH, Liebetrau M, Wunderlich N, Bultemeier G, Nemori R, Hamann GF. Source: Journal of Neuroscience Methods. 2002 May 15; 116(2): 125-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12044662
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A Golgi-Cox morphological analysis of neuronal changes induced by environmental enrichment. Author(s): Faherty CJ, Kerley D, Smeyne RJ. Source: Brain Research. Developmental Brain Research. 2003 March 14; 141(1-2): 55-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12644248
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A H(2)(15)O positron emission tomography study on mental imagery of movement sequences--the effect of modulating sequence length and direction. Author(s): Boecker H, Ceballos-Baumann AO, Bartenstein P, Dagher A, Forster K, Haslinger B, Brooks DJ, Schwaiger M, Conrad B.
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Source: Neuroimage. 2002 October; 17(2): 999-1009. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377173 •
A herbal medicine used in the treatment of addiction mimics the action of amphetamine on in vitro rat striatal dopamine release. Author(s): Thongsaard W, Marsden CA. Source: Neuroscience Letters. 2002 August 30; 329(2): 129-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12165394
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A method of combining biocytin tract-tracing with avidin-biotin-peroxidase complex immunocytochemistry for pre-embedding electron microscopic labeling in neonatal tissue. Author(s): Erisir A, Aoki C. Source: Journal of Neuroscience Methods. 1998 June 1; 81(1-2): 189-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9696325
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A role for amygdaloid PKA and PKC in the acquisition of long-term conditional fear memories in rats. Author(s): Goosens KA, Holt W, Maren S. Source: Behavioural Brain Research. 2000 September; 114(1-2): 145-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10996055
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A specific role for the human amygdala in olfactory memory. Author(s): Buchanan TW, Tranel D, Adolphs R. Source: Learning & Memory (Cold Spring Harbor, N.Y.). 2003 September-October; 10(5): 319-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557604
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Absence of histological lesions in primate models of ECT and magnetic seizure therapy. Author(s): Dwork AJ, Arango V, Underwood M, Ilievski B, Rosoklija G, Sackeim HA, Lisanby SH. Source: The American Journal of Psychiatry. 2004 March; 161(3): 576-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992989
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Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning. Author(s): Wemmie JA, Askwith CC, Lamani E, Cassell MD, Freeman JH Jr, Welsh MJ. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 July 2; 23(13): 5496-502. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12843249
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Acoustic frequency tuning of neurons in the basal forebrain of the waking guinea pig. Author(s): Chernyshev BV, Weinberger NM. Source: Brain Research. 1998 May 18; 793(1-2): 79-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9630532
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Acoustic startle and fear-potentiated startle in rats selectively bred for fast and slow kindling rates: relation to monoamine activity. Author(s): Anisman H, Kelly O, Hayley S, Borowski T, Merali Z, McIntyre DC. Source: The European Journal of Neuroscience. 2000 December; 12(12): 4405-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11122351
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Activation of beta1-adrenoceptors excites striatal cholinergic interneurons through a cAMP-dependent, protein kinase-independent pathway. Author(s): Pisani A, Bonsi P, Centonze D, Martorana A, Fusco F, Sancesario G, De Persis C, Bernardi G, Calabresi P. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 June 15; 23(12): 5272-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832552
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Basal ganglia injury as a complication of the ketogenic diet. Author(s): Erickson JC, Jabbari B, Difazio MP. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2003 April; 18(4): 448-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12671955
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Basal ganglia involvement in sensory and cognitive processing. A depth electrode CNV study in human subjects. Author(s): Bares M, Rektor I. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2001 November; 112(11): 2022-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11682340
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Bilateral metachronous germinoma of the basal ganglia occurring long after total removal of a mature pineal teratoma: case report. Author(s): Sugimoto K, Nakahara I, Nishikawa M. Source: Neurosurgery. 2002 March; 50(3): 613-6; Discussion 616-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11841731
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Comparison of the basal ganglia and cerebellum in shifting attention. Author(s): Ravizza SM, Ivry RB.
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Source: Journal of Cognitive Neuroscience. 2001 April 1; 13(3): 285-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11371307 •
Impaired temporal discrimination in Parkinson's disease: temporal processing of brief durations as an indicator of degeneration of dopaminergic neurons in the basal ganglia. Author(s): Rammsayer T, Classen W. Source: The International Journal of Neuroscience. 1997 September; 91(1-2): 45-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9394214
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Interruption of a basal ganglia-forebrain circuit prevents plasticity of learned vocalizations. Author(s): Brainard MS, Doupe AJ. Source: Nature. 2000 April 13; 404(6779): 762-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10783889
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Light deprivation soon after frontal brain trauma accelerates recovery from attentional deficits and promotes functional normalization of basal ganglia. Author(s): Vargo JM, Grachek RA, Rockswold GL. Source: The Journal of Trauma. 1999 August; 47(2): 265-72; Discussion 273-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10452460
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Processing of temporal information and the basal ganglia: new evidence from fMRI. Author(s): Nenadic I, Gaser C, Volz HP, Rammsayer T, Hager F, Sauer H. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2003 January; 148(2): 238-46. Epub 2002 November 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12520413
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The basal ganglia and semantic engagement: potential insights from semantic priming in individuals with subcortical vascular lesions, Parkinson's disease, and cortical lesions. Author(s): Copland D. Source: Journal of the International Neuropsychological Society : Jins. 2003 November; 9(7): 1041-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14738285
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 basal ganglia; 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 Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.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 BASAL GANGLIA Overview In this chapter, we will give you a bibliography on recent dissertations relating to basal ganglia. 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 “basal ganglia” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on basal ganglia, we have not necessarily excluded nonmedical dissertations in this bibliography.
Dissertations on Basal Ganglia 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 basal ganglia. 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: •
Acetylcholinesterase and the basal ganglia from cytology to function by Lehmann, John; PhD from The University of British Columbia (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK49981
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Anatomical and histochemical studies of the globus pallidus and related basal ganglia nuclei by Staines, William Alan; PhD from The University of British Columbia (Canada), 1983 http://wwwlib.umi.com/dissertations/fullcit/NK66854
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Physiological actions of dopamine in an avian basal ganglia nucleus essential for vocal learning by Ding, Long; PhD from University of Pennsylvania, 2003, 145 pages http://wwwlib.umi.com/dissertations/fullcit/3095876
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The organization of the output of the basal ganglia in rat by Van der Kooy, Derek; PhD from University of Toronto (Canada), 1980 http://wwwlib.umi.com/dissertations/fullcit/NK47169
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The role of the basal ganglia in learning and memory: Evidence from Parkinson's disease by Shohamy, Daphna; PhD from Rutgers the State University of New Jersey Newark, 2003, 182 pages http://wwwlib.umi.com/dissertations/fullcit/3080564
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The role of the basal ganglia in the control of movement by Aldridge, John Wayne; PhD from University of Toronto (Canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK42151
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. BOOKS ON BASAL GANGLIA Overview This chapter provides bibliographic book references relating to basal ganglia. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on basal ganglia include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “basal ganglia” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on basal ganglia: •
Neuroscience for the Study of Communicative Disorders Source: Baltimore, MD: Williams and Wilkins. 1995. 389 p. Contact: Available from Williams and Wilkins. 351 West Camden Street, Baltimore, MD 21201-2436. (800) 638-0672; Fax (800) 447-8438. PRICE: $37.95 plus shipping and handling. ISBN: 0683007408. Summary: This textbook is designed to present the basics of neuroscience to students in communicative disorders and sciences. The authors use concise, simplified descriptions along with extensive illustrations of structures and neuronal connections to explain the anatomy and physiology of the brain. This enables readers to relate functions with structures in both the central and peripheral nervous systems. Twenty chapters cover the scope, principles, and elements of neuroscience; the gross anatomy of the central nervous system (CNS); the internal anatomy of the CNS; the embryological development of the CNS; nerve cells; diencephalon: thalamus and associated structures;
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the somatosensory system; the visual system; the auditory system; the vestibular system; the motor system, including the spinal cord, the cerebellum, the brainstem and basal ganglia, and the cortical level; cranial nerves; the autonomic nervous system, limbic system, hypothalamus, and reticular formation; blood supply; cerebrospinal fluid; the higher mental functions of the cerebral cortex; and diagnostic techniques and neurological concepts. Each chapter includes learning objectives, clinical case studies, summaries, lists of technical terms, review questions, and references. The book concludes with a glossary, appendices, and subject index. (AA-M).
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “basal ganglia” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “basal ganglia” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “basal ganglia” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
The Basal Ganglia and New Surgical Approaches for Parkinson's Disease by Jose A. Obeso, et al; ISBN: 0397517807; http://www.amazon.com/exec/obidos/ASIN/0397517807/icongroupinterna
Chapters on Basal Ganglia In order to find chapters that specifically relate to basal ganglia, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and basal ganglia using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “basal ganglia” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on basal ganglia: •
Copper Metabolism and the Liver Source: in Arias, I.M., et al. Liver: Biology and Pathobiology, Fourth Edition. Philadelphia, PA: Lippincott Williams and Wilkins. 2001. p.331-343. Contact: Available from Lippincott Williams and Wilkins. P.O. Box 1600, Hagerstown, MD 21741. (800) 638-3030 or (301) 223-2300. Fax (301) 223-2365. PRICE: $249.00 plus shipping and handling. ISBN: 0781723906. Summary: Copper is an essential trace element that plays a critical role in the biochemistry of all aerobic organisms. The inherited diseases of copper metabolism underscore both the essential need for copper as well as the toxicity of this metal. This chapter on copper metabolism and the liver is from a textbook on the pathobiology and biology of the liver. The authors note that elucidation of the molecular genetic basis of
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these diseases has revealed a remarkable conservation of the molecular mechanisms of copper metabolism. Wilson disease is an inherited disorder of copper metabolism resulting in hepatic cirrhosis (liver scarring) and basal ganglia degeneration. In humans, copper balance is entirely maintained by gastrointestinal absorption and biliary excretion, and this process is regulated at the stage of hepatocyte efflux of copper by the transport protein encoded at the Wilson locus. The authors cover physiology, cell biology, Wilson disease (genetics, pathogenesis, diagnosis and treatment), and copper associated cirrhosis in childhood. 6 figures. 100 references. •
Laryngeal Electromyography Source: in Sataloff, R.T., ed. Professional Voice: The Science and Art of Clinical Care. 2nd ed. San Diego, CA: Singular Publishing Group, Inc. 1997. p. 245-255. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail:
[email protected]. Website: www.singpub.com. PRICE: $325.00 plus shipping and handling. ISBN: 1565937287. Summary: This chapter on laryngeal electromyography is from a book on the clinical care of the professional voice. Electromyography (EMG) evaluates the integrity of the motor system by recording action potentials generated in the muscle fibers. EMG is particularly useful for evaluating disorders affecting the lower motor neuron, peripheral nerves, neuromuscular junction, and muscle. The authors review the application of EMG in the evaluation of patients with laryngeal disorders. The authors stress that EMG should be considered an extension of the physical examination rather than solely a laboratory procedure. Topics include technique and neurophysiological basis, common abnormal laryngeal EMG findings, and laryngeal EMG abnormalities in specific disease categories, including lower motor neuron and laryngeal nerve disorders, basal ganglia disorders, muscle disorders, disorders of neuromuscular junction, and upper motor neuron disorders. 11 figures. 27 references.
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Wilson's Disease Source: in Okuda, K., ed.,et al. Hepatobiliary Diseases: Pathophysiology and Imaging. Malden, MA: Blackwell Science, Inc. 2001. p. 191-196. Contact: Available from Blackwell Science, Inc. 350 Main Street, Commerce Place, Malden, MA 02148. (800) 215-1000 or (617) 388-8250. Fax (617) 388-8270. E-mail:
[email protected]. Website: www.blackwell- science.com. PRICE: $275.00. ISBN: 0632055421. Summary: Wilson's disease is a rare autosomal recessive disorder characterized by cirrhosis (liver scarring) and basal ganglia (islands of gray matter within each cerebral hemisphere of the brain) degeneration. This chapter on Wilson's disease is from a textbook that familiarizes the reader with various imaging modalities, the information they provide, and the merits of each, in order to facilitate the combined use of different imaging techniques in the diagnosis and management of hepatobiliary (liver and bile tract) diseases. Wilson's disease is caused by copper accumulation in the body, due to the absence or dysfunction of the copper transporting mechanism. The patient develops a greenish-brown pigment ring in the periphery of the cornea known as the KayserFleischer ring. The disease usually presents in childhood, but the diagnosis is often delayed, leading to severe consequences. The disease may present with cirrhosis, aggressive hepatitis, a predominantly hemolytic illness, or acute liver failure with hemolysis (breakdown of red blood cells). In other cases, the disease course consists
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entirely of progressive disintegration of the motor centers of the brain. The authors discuss etiology, pathophysiology, clinical features, diagnosis, and treatment and prognosis. 5 figures. 13 references.
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CHAPTER 6. PERIODICALS AND NEWS ON BASAL GANGLIA Overview In this chapter, we suggest a number of news sources and present various periodicals that cover basal ganglia.
News Services and Press Releases One of the simplest ways of tracking press releases on basal ganglia is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “basal ganglia” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to basal ganglia. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “basal ganglia” (or synonyms). The following was recently listed in this archive for basal ganglia: •
Parkinsonian signs correlate with basal ganglia changes in cirrhosis patients Source: Reuters Medical News Date: September 11, 2000
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Transplantation of neurons safe for patients with basal ganglia stroke Source: Reuters Medical News Date: August 23, 2000
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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “basal ganglia” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “basal ganglia” (or synonyms). If you know the name of a company that is relevant to basal ganglia, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “basal ganglia” (or synonyms).
Academic Periodicals covering Basal Ganglia Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to basal ganglia. In addition to
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these sources, you can search for articles covering basal ganglia that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute8: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
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These publications are typically written by one or more of the various NIH Institutes.
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.9 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:10 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
9
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 10 See http://www.nlm.nih.gov/databases/databases.html.
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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway11 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.12 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “basal ganglia” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 61418 166 129 59 191 61963
HSTAT13 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.14 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.15 Simply search by “basal ganglia” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
11
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
12
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 13 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 14 15
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists16 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.17 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.18 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
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Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Basal Ganglia In the following section, we will discuss databases and references which relate to the Genome Project and basal ganglia. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).19 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 16 Adapted 17
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 18 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 19 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “basal ganglia” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for basal ganglia: •
Calcification of Basal Ganglia with or without Hypocalcemia Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=114100
•
Dandy-walker Malformation with Mental Retardation, Basal Ganglia Disease, and Seizures Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=304340 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
•
Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html
•
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease,
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Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html •
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
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To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “basal ganglia” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database20 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database21 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “basal ganglia” (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word “and” or “or” (using “or” might be useful when using synonyms).
20
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 21 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on basal ganglia can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to basal ganglia. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to basal ganglia. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “basal ganglia”:
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Brain Diseases http://www.nlm.nih.gov/medlineplus/braindiseases.html Huntington's Disease http://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.html Parkinson's Disease http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on basal ganglia. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Huntington's Disease: A Guide for Families Source: New York, NY: Huntington's Disease Society of America. 1996. 24 p. Contact: Available from Huntington's Disease Society of America. 158 West 29th Street, 7th Floor, New York, NY 10001-5300. (800) 345-HDSA or (212) 242-1968. Fax (212) 2432443. E-mail:
[email protected]. Website: neurowww2.mgh.harvard.edu/hsda/hdsamain.nclk. PRICE: Single copy free; $1.00 each for additional copies. Summary: This brochure provides information about Huntington's Disease (HD), a hereditary brain disorder that affects people of all races all over the world. HD is a degenerative disease whose symptoms are caused by the loss of cells in a part of the brain called the basal ganglia. This damage to cells affects cognitive ability, movement, and emotional control. Topics covered include inheritance, the impact of HD on other family members, the symptoms and stages of HD, diagnostic considerations, juvenile HD, being at risk for HD (the psychological impact of knowing one's risk status), genetic testing, treatment, and current research. Initial symptoms of HD can progress to more marked involuntary movements which often lead to problems with walking and balance. Speech and swallowing will be affected. The brochure emphasizes the importance of consulting a speech language pathologist in order to implement coping and communication strategies that can have a positive and lasting impact on the patient's quality of life. The brochure concludes with a description of the Huntington's
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Disease Society of America, a group dedicated to eradicating HD by promoting and supporting HD research; to helping families cope with the problems presented by HD; and to educating the public and professionals about HD. •
Know Your Brain Source: Bethesda, MD: Neurological Institute. 1992. 8 p. Contact: Neurological Institute. P.O. Box 5801, Bethesda, MD 20824. (301) 496-5751 or (800) 352-9424. Summary: This fact sheet presents basic introductory material on the human brain. It describes how the healthy brain works, how to keep it healthy, and what happens when the brain is diseased or dysfunctional. The brain is divided into the forebrain, midbrain, and hindbrain. The hindbrain, including the cerebellum, the brain stem, and the upper part of the spinal cord, controls the body's vital functions, such as respiration and heart rate, as well as movements learned by rote. The midbrain controls some reflex actions and voluntary movements, and the forebrain enables thought and memory storage. The portions of the brain responsible for thoughts, sensations, and voluntary movements comprise the frontal, parietal, occipital, and temporal lobes. The cerebral cortex, or coating of the brain, is where information processing occurs. The inner brain, including the hypothalamus, thalamus, hippocampus, and basal ganglia, controls emotional states and perceptions. Structures connecting these major parts of the brain are the dendrites, axons, and axonal sheath, which acts as an insulator. Neurotransmitters help signals move from nerve cell to nerve cell and are secreted by sacs at the ends of axons. Common neurotransmitters are acetylcholine, gamma- aminobutyric acid, serotonin, and dopamine. Neurological disorders, including Alzheimer's disease, are listed that alter the brain's ability to function properly. 7 figures.
•
Huntington's Disease: Facts At a Glance Source: New York, NY: Huntington's Disease Society of America. 1997. 2 p. Contact: Available from Huntington's Disease Society of America. 158 West 29th Street, 7th Floor, New York, NY 10001-5300. (800) 345-HDSA or (212) 242-1968. Fax (212) 2432443. E-mail:
[email protected]. Website: neurowww2.mgh.harvard.edu/hsda/hdsamain.nclk. PRICE: Single copy free. Summary: This fact sheet provides information about Huntington's Disease (HD), a hereditary brain disorder that affects people of all races all over the world. HD is a degenerative disease whose symptoms are caused by the loss of cells in a part of the brain called the basal ganglia. This damage to cells affects cognitive ability, movement, and emotional control. Topics covered include inheritance, the symptoms of HD, the affected population, diagnostic considerations, genetic testing, treatment, and current research. The fact sheet concludes with a description of the Huntington's Disease Society of America, a not for profit national voluntary health organization which funds research and operates education, advocacy, and family service programs through a nationwide network of chapters, affiliates, and support groups. The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate
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in some way to basal ganglia. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to basal ganglia. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with basal ganglia. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about basal ganglia. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine.
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To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “basal ganglia” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “basal ganglia”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “basal ganglia” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “basal ganglia” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
22
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
•
Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
•
Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
•
Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
•
Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
•
Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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•
Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
•
Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
•
Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
•
Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
•
Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
•
Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
•
Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
•
Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
•
National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
•
National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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•
Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
•
New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
•
New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
•
Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
•
Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
•
Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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•
South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
•
Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
•
Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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BASAL GANGLIA DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Abscess: A localized, circumscribed collection of pus. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acidemia: Increased acidity of blood. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH]
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Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low
Dictionary 155
serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral
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ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Angiography: Radiography of blood vessels after injection of a contrast medium. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anophthalmia: Absence of an eye or eyes in the newborn due to failure of development of the optic cup or to disappearance of the eyes after partial development. [NIH] Ansa: A turn or bend in a thread or line; a bend in a wire; one of the patterns formed by the dermal ridges on the finger tips. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
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Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-infective: An agent that so acts. [EU] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic
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and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antiviral: Destroying viruses or suppressing their replication. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Arteriovenous Fistula: An abnormal communication between an artery and a vein. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Asphyxia: A pathological condition caused by lack of oxygen, manifested in impending or actual cessation of life. [NIH] Aspiration: The act of inhaling. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the
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biological or pharmacological potency of a drug. [EU] Asterixis: A motor disturbance marked by intermittency of sustained contraction of groups of muscles. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Avian: A plasmodial infection in birds. [NIH]
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Avidin: A specific protein in egg albumin that interacts with biotin to render it unavailable to mammals, thereby producing biotin deficiency. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Axotomy: Transection or severing of an axon. This type of denervation is used often in experimental studies on neuronal physiology and neuronal death or survival, toward an understanding of nervous system disease. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basalis: Chiasmatic cistern. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]
Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Bicuculline: Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bile duct: A tube through which bile passes in and out of the liver. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU]
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Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotin: Hexahydro-2-oxo-1H-thieno(3,4-d)imidazole-4-pentanoic acid. Growth factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.The biotin content of cancerous tissue is higher than that of normal tissue. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types,
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yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Bradykinesia: Abnormal slowness of movement; sluggishness of physical and mental responses. [EU] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bruxism: A disorder characterized by grinding and clenching of the teeth. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Butyric Acid: A four carbon acid, CH3CH2CH2COOH, with an unpleasant odor that occurs in butter and animal fat as the glycerol ester. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcitonin: A peptide hormone that lowers calcium concentration in the blood. In humans, it is released by thyroid cells and acts to decrease the formation and absorptive activity of osteoclasts. Its role in regulating plasma calcium is much greater in children and in certain diseases than in normal adults. [NIH] Calcitonin Gene-Related Peptide: Calcitonin gene-related peptide. A 37-amino acid peptide derived from the calcitonin gene. It occurs as a result of alternative processing of mRNA from the calcitonin gene. The neuropeptide is widely distributed in neural tissue of the brain, gut, perivascular nerves, and other tissue. The peptide produces multiple biological effects and has both circulatory and neurotransmitter modes of action. In particular, it is a potent endogenous vasodilator. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH]
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Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins or activator proteins. [NIH] Calibration: Determination, by measurement or comparison with a standard, of the correct value of each scale reading on a meter or other measuring instrument; or determination of the settings of a control device that correspond to particular values of voltage, current, frequency, or other output. [NIH] Cannabidiol: Compound isolated from Cannabis sativa extract. [NIH] Cannabinoids: Compounds extracted from Cannabis sativa L. and metabolites having the cannabinoid structure. The most active constituents are tetrahydrocannabinol, cannabinol, and cannabidiol. [NIH] Cannabinol: A physiologically inactive constituent of Cannabis sativa L. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxy: Cannabinoid. [NIH] Carcinoembryonic Antigen: A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the respone to colon cancer treatment. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Carotenoids: Substance found in yellow and orange fruits and vegetables and in dark green, leafy vegetables. May reduce the risk of developing cancer. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cat-Scratch Disease: A self-limiting bacterial infection of the regional lymph nodes caused by Afipia felis, a gram-negative bacterium recently identified by the Centers for Disease Control and Prevention and by Bartonella henselae. It usually arises one or more weeks
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following a feline scratch, with raised inflammatory nodules at the site of the scratch being the primary symptom. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH]
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Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Ceroid: A naturally occurring lipid pigment with histochemical characteristics similar to lipofuscin. It accumulates in various tissues in certain experimental and pathological conditions. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chelation: Combination with a metal in complexes in which the metal is part of a ring. [EU] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is
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also a frequent manifestation of basal ganglia diseases. [NIH] Choreatic Disorders: Acquired and hereditary conditions which feature chorea as a primary manifestation of the disease process. [NIH] Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Choroid Plexus: A villous structure of tangled masses of blood vessels contained within the third, lateral, and fourth ventricles of the brain. It regulates part of the production and composition of cerebrospinal fluid. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cleft Lip: Congenital defect in the upper lip where the maxillary prominence fails to merge with the merged medial nasal prominences. It is thought to be caused by faulty migration of the mesoderm in the head region. [NIH] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Clozapine: A tricylic dibenzodiazepine, classified as an atypical antipsychotic agent. It binds several types of central nervous system receptors, and displays a unique pharmacological profile. Clozapine is a serotonin antagonist, with strong binding to 5-HT 2A/2C receptor subtype. It also displays strong affinity to several dopaminergic receptors, but shows only weak antagonism at the dopamine D2 receptor, a receptor commonly thought to modulate neuroleptic activity. Agranulocytosis is a major adverse effect associated with
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administration of this agent. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. [NIH] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Comatose: Pertaining to or affected with coma. [EU] Common Variable Immunodeficiency: Heterogeneous group of immunodeficiency syndromes characterized by hypogammaglobulinemia of most isotypes, variable B-cell defects, and the presence of recurrent bacterial infections. [NIH] Compacta: Part of substantia nigra. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the
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classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cones: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide sharp central vision and color vision. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH]
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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]
Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Contralateral: Having to do with the opposite side of the body. [NIH] Contrast Media: Substances used in radiography that allow visualization of certain tissues. [NIH]
Contrast medium: A substance that is introduced into or around a structure and, because of the difference in absorption of x-rays by the contrast medium and the surrounding tissues, allows radiographic visualization of the structure. [EU] Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corpus: The body of the uterus. [NIH] Corpus Striatum: Striped gray and white matter consisting of the neostriatum and paleostriatum (globus pallidus). It is located in front of and lateral to the thalamus in each cerebral hemisphere. The gray substance is made up of the caudate nucleus and the lentiform nucleus (the latter consisting of the globus pallidus and putamen). The white
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matter is the internal capsule. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Cranial Nerves: Twelve pairs of nerves that carry general afferent, visceral afferent, special afferent, somatic efferent, and autonomic efferent fibers. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclopia: Elements of the two eyes fused into one median eye in the center of the forehead of a fetal monster. [NIH] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cyst: A sac or capsule filled with fluid. [NIH] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeletal Proteins: Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible. [NIH]
Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced
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ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU]
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Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [NIH] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy;
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superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Duodenum: The first part of the small intestine. [NIH] Dura mater: The outermost, toughest, and most fibrous of the three membranes (meninges) covering the brain and spinal cord; called also pachymeninx. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efferent Pathways: Nerve structures through which impulses are conducted from a nerve center toward a peripheral site. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolytes: Substances that break up into ions (electrically charged particles) when they are dissolved in body fluids or water. Some examples are sodium, potassium, chloride, and calcium. Electrolytes are primarily responsible for the movement of nutrients into cells, and the movement of wastes out of cells. [NIH] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH]
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Electroretinogram: The electrical effect recorded from the surface of the eyeball and originated by a pulse of light. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]
Emetic: An agent that causes vomiting. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Encephalitis, Viral: Inflammation of brain parenchymal tissue as a result of viral infection. Encephalitis may occur as primary or secondary manifestation of Togaviridae infections; Herpesviridae infections; Adenoviridae infections; Flaviviridae infections; Bunyaviridae infections; Picornaviridae infections; Paramyxoviridae infections; Orthomyxoviridae infections; Retroviridae infections; and Arenaviridae infections. [NIH] Encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium,
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vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxin: Toxin from cell walls of bacteria. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Entopeduncular Nucleus: A portion of the nucleus of ansa lenticularis located medial to the posterior limb of the internal capsule, along the course of the ansa lenticularis and the inferior thalamic peduncle or as a separate nucleus within the internal capsule adjacent to the medial globus pallidus. (NeuroNames, http://rprcsgi.rprc. washington.edu/neuronames/ (September 28, 1998)) In non-primates, the entopeduncular nucleus is analogous to both the medial globus pallidus and the entopeduncular nucleus of human. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Ependymal: It lines the cavities of the brain's ventricles and the spinal cord and slowly divides to create a stem cell. [NIH] Ependymal tumors: A type of brain tumor that usually begins in the central canal of the spinal cord. Ependymomas may also develop in the cells lining the ventricles of the brain, which produce and store the special fluid (cerebrospinal fluid) that protects the brain and spinal cord. Also called ependymomas. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei
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although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocyte Volume: Volume of circulating erythrocytes. It is usually measured by radioisotope dilution technique. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogens: A class of sex hormones associated with the development and maintenance of secondary female sex characteristics and control of the cyclical changes in the reproductive cycle. They are also required for pregnancy maintenance and have an anabolic effect on protein metabolism and water retention. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitotoxicity: Excessive exposure to glutamate or related compounds can kill brain neurons, presumably by overstimulating them. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Exploratory Behavior: The tendency to explore or investigate a novel environment. It is considered a motivation not clearly distinguishable from curiosity. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of
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macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraocular: External to or outside of the eye. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]
Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrin: A protein derived from fibrinogen in the presence of thrombin, which forms part of the blood clot. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process
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whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flexor: Muscles which flex a joint. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Foramen: A natural hole of perforation, especially one in a bone. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fossa: A cavity, depression, or pit. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
Fungicide: An agent that destroys fungi. [EU] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene
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action. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Germinoma: The most frequent type of germ-cell tumor in the brain. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestures: Movement of a part of the body for the purpose of communication. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glial tumors: A general term for many types of tumors of the central nervous system, including astrocytomas, ependymal tumors, glioblastoma multiforme, and primitive neuroectodermal tumors. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glioblastoma multiforme: A type of brain tumor that forms from glial (supportive) tissue of the brain. It grows very quickly and has cells that look very different from normal cells. Also called grade IV astrocytoma. [NIH] Glioma: A cancer of the brain that comes from glial, or supportive, cells. [NIH] Gliosis: The production of a dense fibrous network of neuroglia; includes astrocytosis, which is a proliferation of astrocytes in the area of a degenerative lesion. [NIH] Globus Pallidus: The representation of the phylogenetically oldest part of the corpus striatum called the paleostriatum. It forms the smaller, more medial part of the lentiform nucleus. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH]
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Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]
Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanine: One of the four DNA bases. [NIH] Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH]
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Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Hallucinogens: Drugs capable of inducing illusions, hallucinations, delusions, paranoid ideations, and other alterations of mood and thinking. Despite the name, the feature that distinguishes these agents from other classes of drugs is their capacity to induce states of altered perception, thought, and feeling that are not experienced otherwise. [NIH] Haloperidol: Butyrophenone derivative. [NIH] Handedness: Preference for using right or left hand. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hemiatrophy: Progressive atrophy of all structures of one side of the face, including skin, subcutaneous tissue, muscle and bone. [NIH] Hemicrania: An ache or a pain in one side of the head, as in migraine. [NIH] Hemiparesis: The weakness or paralysis affecting one side of the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemoglobinopathies: A group of inherited disorders characterized by structural alterations within the hemoglobin molecule. [NIH] Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemolytic: A disease that affects the blood and blood vessels. It destroys red blood cells, cells that cause the blood to clot, and the lining of blood vessels. HUS is often caused by the Escherichia coli bacterium in contaminated food. People with HUS may develop acute renal failure. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemorrhagic stroke: A disorder involving bleeding within ischemic brain tissue. Hemorrhagic stroke occurs when blood vessels that are damaged or dead from lack of blood supply (infarcted), located within an area of infarcted brain tissue, rupture and transform an "ischemic" stroke into a hemorrhagic stroke. Ischemia is inadequate tissue oxygenation
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caused by reduced blood flow; infarction is tissue death resulting from ischemia. Bleeding irritates the brain tissues, causing swelling (cerebral edema). Blood collects into a mass (hematoma). Both swelling and hematoma will compress and displace brain tissue. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatic Encephalopathy: A condition that may cause loss of consciousness and coma. It is usually the result of advanced liver disease. Also called hepatic coma. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatobiliary: Pertaining to the liver and the bile or the biliary ducts. [EU] Hepatocyte: A liver cell. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]
Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Histone Deacetylase: Hydrolyzes N-acetyl groups on histones. [NIH] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Holoprosencephaly: Anterior midline brain, cranial, and facial malformations resulting from the failure of the embryonic prosencephalon to undergo segmentation and cleavage. Alobar prosencephaly is the most severe form and features anophthalmia; cyclopia; severe mental retardation; cleft lip; cleft palate; seizures; and microcephaly. Semilobar holoprosencepaly is characterized by hypotelorism, microphthalmia, coloboma, nasal malformations, and variable degrees of mental retardation. Lobar holoprosencephaly is associated with mild (or absent) facial malformations and intellectual abilities that range from mild mental retardation to normal. Holoprosencephlay is associated with chromosome abnormalities. [NIH]
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Homeobox: Distinctive sequence of DNA bases. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hypercalcemia: Abnormally high level of calcium in the blood. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hyperreflexia: Exaggeration of reflexes. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypogammaglobulinemia: The most common primary immunodeficiency in which antibody production is deficient. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH]
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Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunosuppression: Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive Agents: Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of suppressor T-cell populations or by inhibiting the activation of helper cells. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of interleukins and other cytokines are emerging. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU]
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Incubation period: The period of time likely to elapse between exposure to the agent of the disease and the onset of clinical symptoms. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insecticides: Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics. [NIH] Insertional: A technique in which foreign DNA is cloned into a restriction site which occupies a position within the coding sequence of a gene in the cloning vector molecule. Insertion interrupts the gene's sequence such that its original function is no longer expressed. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH]
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Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Capsule: White matter pathway, flanked by nuclear masses, consisting of both afferent and efferent fibers projecting between the cerebral cortex and the brainstem. It consists of three distinct parts: an anterior limb, posterior limb, and genu. [NIH] Interneurons: Most generally any neurons which are not motor or sensory. Interneurons may also refer to neurons whose axons remain within a particular brain region as contrasted with projection neurons which have axons projecting to other brain regions. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Involuntary: Reaction occurring without intention or volition. [NIH] Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ion Exchange: Reversible chemical reaction between a solid, often an ION exchange resin, and a fluid whereby ions may be exchanged from one substance to another. This technique is used in water purification, in research, and in industry. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iontophoresis: Therapeutic introduction of ions of soluble salts into tissues by means of electric current. In medical literature it is commonly used to indicate the process of increasing the penetration of drugs into surface tissues by the application of electric current. It has nothing to do with ion exchange, air ionization nor phonophoresis, none of which requires current. [NIH] Ipsilateral: Having to do with the same side of the body. [NIH]
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Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lateral Ventricles: Cavity in each of the cerebral hemispheres derived from the cavity of the embryonic neural tube. They are separated from each other by the septum pellucidum, and each communicates with the third ventricle by the foramen of Monro, through which also the choroid plexuses of the lateral ventricles become continuous with that of the third ventricle. [NIH] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH] Lentivirus: A genus of the family Retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (ORFs) between the pol and env genes and in the 3' env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levodopa: The naturally occurring form of dopa and the immediate precursor of dopamine. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to dopamine. It is used for the treatment of parkinsonism and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]
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Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipofuscin: A naturally occurring lipid pigment with histochemical characteristics similar to ceroid. It accumulates in various normal tissues and apparently increases in quantity with age. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]
Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver Cirrhosis: Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Lobule: A small lobe or subdivision of a lobe. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH]
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Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lycopene: A red pigment found in tomatoes and some fruits. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Depletion: Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation. [NIH] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Macroglia: A type of neuroglia composed of astrocytes. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macula: A stain, spot, or thickening. Often used alone to refer to the macula retinae. [EU] Macula Lutea: An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the superior pole of the eye and slightly below the level of the optic disk. [NIH] Macular Degeneration: Degenerative changes in the macula lutea of the retina. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of
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radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mammogram: An x-ray of the breast. [NIH] Maneb: Manganese derivative of ethylenebisdithiocarbamate. It is used in agriculture as a fungicide and has been shown to cause irritation to the eyes, nose, skin, and throat. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manic-depressive psychosis: One of a group of psychotic reactions, fundamentally marked by severe mood swings and a tendency to remission and recurrence. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e., extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Median Nerve: A major nerve of the upper extremity. In humans, the fibers of the median nerve originate in the lower cervical and upper thoracic spinal cord (usually C6 to T1), travel via the brachial plexus, and supply sensory and motor innervation to parts of the forearm and hand. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH]
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Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Meningitis: Inflammation of the meninges. When it affects the dura mater, the disease is termed pachymeningitis; when the arachnoid and pia mater are involved, it is called leptomeningitis, or meningitis proper. [EU] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metabotropic: A glutamate receptor which triggers an increase in production of 2 intracellular messengers: diacylglycerol and inositol 1, 4, 5-triphosphate. [NIH] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions
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and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methylprednisolone: (6 alpha,11 beta)-11,17,21-Trihydroxy-6-methylpregna-1,4-diene-3,2dione. A prednisolone derivative which has pharmacological actions similar to prednisolone. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Microcirculation: The vascular network lying between the arterioles and venules; includes capillaries, metarterioles and arteriovenous anastomoses. Also, the flow of blood through this network. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Micturition: The passage of urine; urination. [EU] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH]
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Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motility: The ability to move spontaneously. [EU] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Motor Skills: Performance of complex motor acts. [NIH] Movement Disorders: Syndromes which feature dyskinesias as a cardinal manifestation of the disease process. Included in this category are degenerative, hereditary, post-infectious, medication-induced, post-inflammatory, and post-traumatic conditions. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's
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immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscular Atrophy: Derangement in size and number of muscle fibers occurring with aging, reduction in blood supply, or following immobilization, prolonged weightlessness, malnutrition, and particularly in denervation. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neostriatum: The phylogenetically newer part of the corpus striatum consisting of the caudate nucleus and putamen. It is often called simply the striatum. [NIH] Nephropathy: Disease of the kidneys. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules).
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These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neurogenic Inflammation: Inflammation caused by an injurious stimulus of peripheral neurons and resulting in release of neuropeptides which affect vascular permeability and help initiate proinflammatory and immune reactions at the site of injury. [NIH] Neuroglia: The non-neuronal cells of the nervous system. They are divided into macroglia (astrocytes, oligodendroglia, and schwann cells) and microglia. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the blood-brain and blood-retina barriers, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologic Manifestations: Clinical signs and symptoms caused by nervous system injury or dysfunction. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurophysiology: The scientific discipline concerned with the physiology of the nervous system. [NIH] Neuropil: A dense intricate feltwork of interwoven fine glial processes, fibrils, synaptic
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terminals, axons, and dendrites interspersed among the nerve cells in the gray matter of the central nervous system. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurosurgical Procedures: Surgery performed on the nervous system or its parts. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotoxin: A substance that is poisonous to nerve tissue. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the
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next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occipital Lobe: Posterior part of the cerebral hemisphere. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Oncogenic: Chemical, viral, radioactive or other agent that causes cancer; carcinogenic. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Open Reading Frames: Reading frames where successive nucleotide triplets can be read as codons specifying amino acids and where the sequence of these triplets is not interrupted by stop codons. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]
Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU]
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Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoclasts: A large multinuclear cell associated with the absorption and removal of bone. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in cementum resorption. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overdosage: 1. The administration of an excessive dose. 2. The condition resulting from an excessive dose. [EU] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [EU] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Pachymeningitis: Inflammation of the dura mater of the brain, the spinal cord or the optic nerve. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Pancreatic Insufficiency: Absence of or reduced pancreatic exocrine secretion into the duodenum and resultant poor digestion of lipids, vitamins, nitrogen, and carbohydrates. [NIH]
Paralysis: Loss of ability to move all or part of the body. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal,
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intravenous, etc. [EU] Parenteral Nutrition: The administering of nutrients for assimilation and utilization by a patient who cannot maintain adequate nutrition by enteral feeding alone. Nutrients are administered by a route other than the alimentary canal (e.g., intravenously, subcutaneously). [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pedigree: A record of one's ancestors, offspring, siblings, and their offspring that may be used to determine the pattern of certain genes or disease inheritance within a family. [NIH] Peduncle: A narrow supporting part, a stem. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Pergolide: A long-acting dopamine agonist which is effective in the treatment of Parkinson's disease and hyperprolactinemia. It has also been observed to have antihypertensive effects. [NIH]
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Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Neuropathy: Nerve damage, usually affecting the feet and legs; causing pain, numbness, or a tingling feeling. Also called "somatic neuropathy" or "distal sensory polyneuropathy." [NIH] Perivascular: Situated around a vessel. [EU] Periventricular Leukomalacia: Rare form of epilepsy. [NIH] Peroxidase: A hemeprotein from leukocytes. Deficiency of this enzyme leads to a hereditary disorder coupled with disseminated moniliasis. It catalyzes the conversion of a donor and peroxide to an oxidized donor and water. EC 1.11.1.7. [NIH] Peroxide: Chemical compound which contains an atom group with two oxygen atoms tied to each other. [NIH] Pesticides: Chemicals used to destroy pests of any sort. The concept includes fungicides (industrial fungicides), insecticides, rodenticides, etc. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] Phagocytosis: The engulfing of microorganisms, other cells, and foreign particles by phagocytic cells. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenylbutyrate: An anticancer drug that belongs to the family of drugs called differentiating agents. [NIH] Phobias: An exaggerated and invariably pathological dread of some specific type of
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stimulus or situation. [NIH] Phonophoresis: Use of ultrasound to increase the percutaneous adsorption of drugs. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylates: Attached to a phosphate group. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in
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phylogenetic studies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Pontine: A brain region involved in the detection and processing of taste. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Portosystemic Shunt: An operation to create an opening between the portal vein and other veins around the liver. [NIH] Positive End-Expiratory Pressure: A method of mechanical ventilation in which pressure is maintained to increase the volume of gas remaining in the lung at the end of expiration, thus keeping the alveoli open and improving gas exchange. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Postural: Pertaining to posture or position. [EU] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the
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convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Prenatal Diagnosis: Determination of the nature of a pathological condition or disease in the postimplantation embryo, fetus, or pregnant female before birth. [NIH] Preoperative: Preceding an operation. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Primitive neuroectodermal tumors: PNET. A type of bone cancer that forms in the middle (shaft) of large bones. Also called Ewing's sarcoma/primitive neuroectodermal tumor. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Prosencephalon: The part of the brain developed from the most rostral of the three primary vesicles of the embryonic neural tube and consisting of the diencephalon and telencephalon. [NIH]
Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests
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upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protease Inhibitors: Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]
Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity;
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usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Punishment: The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Putamen: The largest and most lateral of the basal ganglia lying between the lateral medullary lamina of the globus pallidus and the external capsule. It is part of the neostriatum and forms part of the lentiform nucleus along with the globus pallidus. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quinolinic: It is produced by immune cells and slowly infiltrates the brain tissues after an injury. [NIH] Quinolinic Acid: 2,3-Pyridinedicarboxylic acid. A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are significantly correlated with the severity of neuropsychological deficits in patients who have AIDS. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH]
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Radiography: Examination of any part of the body for diagnostic purposes by means of roentgen rays, recording the image on a sensitized surface (such as photographic film). [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Radiology: A specialty concerned with the use of x-ray and other forms of radiant energy in the diagnosis and treatment of disease. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Raphe Nuclei: Collections of small neurons centrally scattered among many fibers from the level of the trochlear nucleus in the midbrain to the hypoglossal area in the medulla oblongata. [NIH] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego function. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Chemokine: Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the chemokines themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH]
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Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regional lymph node: In oncology, a lymph node that drains lymph from the region around a tumor. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Research Support: Financial support of research activities. [NIH] Resected: Surgical removal of part of an organ. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory distress syndrome: A lung disease that occurs primarily in premature infants; the newborn must struggle for each breath and blueing of its skin reflects the baby's inability to get enough oxygen. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal pigment epithelium: The pigment cell layer that nourishes the retinal cells; located just outside the retina and attached to the choroid. [NIH] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve
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(neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retinopathy: 1. Retinitis (= inflammation of the retina). 2. Retinosis (= degenerative, noninflammatory condition of the retina). [EU] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents. [NIH]
Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport. [NIH]
Rubella: An acute, usually benign, infectious disease caused by a togavirus and most often affecting children and nonimmune young adults, in which the virus enters the respiratory tract via droplet nuclei and spreads to the lymphatic system. It is characterized by a slight cold, sore throat, and fever, followed by enlargement of the postauricular, suboccipital, and cervical lymph nodes, and the appearances of a fine pink rash that begins on the head and spreads to become generalized. Called also German measles, roetln, röteln, and three-day measles, and rubeola in French and Spanish. [EU] Saccades: An abrupt voluntary shift in ocular fixation from one point to another, as occurs in reading. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH]
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Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segmentation: The process by which muscles in the intestines move food and wastes through the body. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senescence: The bodily and mental state associated with advancing age. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Septum: A dividing wall or partition; a general term for such a structure. The term is often used alone to refer to the septal area or to the septum pellucidum. [EU] Septum Pellucidum: A triangular double membrane separating the anterior horns of the lateral ventricles of the brain. It is situated in the median plane and bounded by the corpus callosum and the body and columns of the fornix. [NIH] Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins
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have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Sex Determination: The biological characteristics which distinguish human beings as female or male. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Shunt: A surgically created diversion of fluid (e.g., blood or cerebrospinal fluid) from one area of the body to another area of the body. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata
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associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Songbirds: Passeriformes of the suborder, Oscines, in which the flexor tendons of the toes are separate, and the lower syrinx has 4 to 9 pairs of tensor muscles inserted at both ends of the tracheal half rings. They include many commonly recognized birds such as crows, finches, robins, sparrows, and swallows. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech Perception: The process whereby an utterance is decoded into a representation in terms of linguistic units (sequences of phonetic segments which combine to form lexical and grammatical morphemes). [NIH] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Steady state: Dynamic equilibrium. [EU] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH]
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Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stria: 1. A streak, or line. 2. A narrow bandlike structure; a general term for such longitudinal collections of nerve fibres in the brain. [EU] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subliminal: Below the threshold of sensation, as a subliminal stimulus. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Sumatriptan: A serotonin agonist that acts selectively at 5HT1 receptors. It is used in the treatment of migraines. [NIH] Superoxide: Derivative of molecular oxygen that can damage cells. [NIH] Superoxide Dismutase: An oxidoreductase that catalyzes the reaction between superoxide anions and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. EC 1.15.1.1. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Supratentorial: Located in the upper part of the brain. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's
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response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Syrinx: A fistula. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratoma: A type of germ cell tumor that may contain several different types of tissue, such as hair, muscle, and bone. Teratomas occur most often in the ovaries in women, the testicles in men, and the tailbone in children. Not all teratomas are malignant. [NIH] Terminalis: A groove on the lateral surface of the right atrium. [NIH]
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Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Thalamic: Cell that reaches the lateral nucleus of amygdala. [NIH] Thalamic Diseases: Disorders of the centrally located thalamus, which integrates a wide range of cortical and subcortical information. Manifestations include sensory loss, movement disorders; ataxia, pain syndromes, visual disorders, a variety of neuropsychological conditions, and coma. Relatively common etiologies include cerebrovascular disorders; craniocerebral trauma; brain neoplasms; brain hypoxia; intracranial hemorrhages; and infectious processes. [NIH] Thalamic Nuclei: Several groups of nuclei in the thalamus that serve as the major relay centers for sensory impulses in the brain. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Third Ventricle: A narrow cleft inferior to the corpus callosum, within the diencephalon, between the paired thalami. Its floor is formed by the hypothalamus, its anterior wall by the lamina terminalis, and its roof by ependyma. It communicates with the fourth ventricle by the cerebral aqueduct, and with the lateral ventricles by the interventricular foramina. [NIH] Thoracic: Having to do with the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts plasminogen to plasmin. It has fibrin-binding activity and is immunologically different from urinary plasminogen activator. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases. EC 3.4.21.68. [NIH]
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Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonicity: The normal state of muscular tension. [NIH] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell
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to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Trophic: Of or pertaining to nutrition. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tuberous Sclerosis: A rare congenital disease in which the essential pathology is the appearance of multiple tumors in the cerebrum and in other organs, such as the heart or kidneys. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urodynamics: The mechanical laws of fluid dynamics as they apply to urine transport. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vacuoles: Any spaces or cavities within a cell. They may function in digestion, storage, secretion, or excretion. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.
Dictionary 217
[NIH]
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Headaches: A group of disorders characterized by recurrent headaches associated with abnormal dilation and constriction of cerebral blood vessels. Representative disorders from this category include migraine, cluster headache, and paroxysmal hemicrania. [NIH] Vasculitis: Inflammation of a blood vessel. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Viral Proteins: Proteins found in any species of virus. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH]
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Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitamin A: A substance used in cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
219
INDEX 3 3-dimensional, 49, 153 A Abdomen, 153, 188, 198, 212 Aberrant, 29, 153 Ablation, 38, 68, 72, 153 Abscess, 153, 209 Acceptor, 153, 188, 198 Acetylcholine, 7, 11, 22, 52, 141, 153, 165, 196 Acidemia, 91, 94, 153 Acquired Immunodeficiency Syndrome, 10, 70, 153 Actin, 153, 194, 195 Action Potentials, 123, 153 Acute renal, 153, 181 Acyl, 54, 153 Acylation, 54, 153 Adaptability, 24, 153, 164 Adaptation, 39, 42, 97, 153, 196, 201 Adenine, 153, 154 Adenosine, 6, 11, 22, 51, 154, 184, 201 Adjustment, 42, 153, 154 Adolescence, 18, 154 Adrenergic, 154, 156, 157, 172, 175, 213 Adverse Effect, 154, 158, 166, 210 Aerobic, 122, 154, 192 Afferent, 18, 45, 46, 51, 154, 170, 186, 203, 209 Affinity, 154, 159, 166, 195 Age of Onset, 24, 154 Agonist, 12, 13, 24, 110, 154, 158, 172, 199, 212 Airway, 52, 154 Akathisia, 66, 154, 158 Akinesia, 22, 23, 154 Albumin, 154, 160 Algorithms, 155, 161 Alimentary, 155, 186, 198, 199 Alkaline, 155, 162 Alkaloid, 155, 160, 167, 193 Alleles, 155, 182 Allergen, 155, 171, 209 Alpha-fetoprotein, 82, 155, 177 Alternative medicine, 126, 155 Alveoli, 155, 202, 217 Amine, 155, 182 Amino Acid Sequence, 155, 157
Amino Acids, 93, 155, 195, 197, 199, 202, 204, 208, 209, 214, 215 Ammonia, 32, 155, 180 Amphetamine, 7, 23, 44, 50, 115, 155, 171 Amygdala, 39, 40, 48, 58, 114, 115, 155, 160, 188, 209, 214 Anaesthesia, 156, 185 Anal, 156, 175, 177, 188 Analogous, 156, 175, 215 Analysis of Variance, 58, 156 Anaphylatoxins, 156, 168 Anatomical, 7, 10, 18, 20, 22, 24, 43, 62, 63, 65, 66, 119, 156, 159, 165, 184, 192, 208 Anemia, 137, 156 Anesthesia, 154, 156, 203 Angiography, 3, 156 Animal model, 8, 13, 17, 21, 22, 53, 55, 59, 62, 156 Anions, 154, 156, 186, 212 Anophthalmia, 156, 182 Ansa, 156, 175 Antagonism, 22, 156, 166 Anti-Anxiety Agents, 156, 205, 215 Antibacterial, 156, 211 Antibiotic, 156, 199, 211 Antibodies, 47, 157, 181, 184, 193, 201 Antibody, 154, 157, 167, 183, 185, 190, 193, 205, 209, 211 Anticoagulant, 157, 204 Antidepressant, 41, 57, 157, 178 Antidepressive Agents, 157, 205 Antiemetic, 157, 158 Antigen, 154, 157, 167, 183, 184, 185, 190, 192, 209 Antigen-Antibody Complex, 157, 167 Antihypertensive, 157, 199 Anti-infective, 157, 183, 186 Antimetabolite, 157, 171 Antioxidant, 49, 157, 198 Antipsychotic, 6, 15, 43, 157, 158, 166, 195, 208, 215 Antipsychotic Agents, 6, 16, 158, 215 Antiviral, 158, 171 Anus, 156, 158, 167, 186 Anxiety, 48, 154, 156, 158, 197 Aorta, 158, 163, 217 Apathy, 158, 195 Aphasia, 76, 105, 158
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Apomorphine, 12, 99, 158 Apoptosis, 9, 28, 66, 158 Applicability, 60, 158 Approximate, 16, 158 Aqueous, 158, 160, 170, 174, 183 Arginine, 156, 158, 182, 196 Arterial, 158, 169, 183, 204, 213 Arteriovenous, 67, 73, 77, 82, 100, 106, 158, 192 Arteriovenous Fistula, 106, 158 Artery, 158, 161, 174, 177, 205, 217 Asphyxia, 93, 158 Aspiration, 94, 95, 103, 158, 177 Assay, 51, 158 Asterixis, 32, 159 Astrocytes, 28, 159, 179, 189, 192, 193, 195 Asymptomatic, 56, 159 Ataxia, 98, 136, 137, 159, 164, 214 Atrial, 159, 169, 216 Atrioventricular, 159, 169 Atrium, 159, 163, 169, 213, 216, 217 Atrophy, 4, 5, 67, 88, 97, 136, 137, 159, 181, 194 Attenuated, 23, 159 Attenuation, 7, 159 Atypical, 6, 43, 159, 166, 208 Auditory, 27, 35, 41, 42, 122, 159, 203 Autoimmune disease, 49, 159, 193 Autoimmunity, 67, 77, 159 Autonomic Nervous System, 67, 122, 159, 200, 211, 212 Autopsy, 68, 74, 159 Autoradiography, 110, 159 Avian, 35, 119, 159 Avidin, 115, 160 Axons, 48, 88, 141, 160, 171, 186, 196, 197, 200 Axotomy, 52, 160 B Bacteria, 153, 156, 157, 160, 174, 175, 177, 180, 181, 189, 192, 206, 211, 215, 216 Bacterial Infections, 160, 167 Bacterial Physiology, 153, 160 Bacterium, 160, 163, 181 Basalis, 114, 160 Base, 45, 153, 160, 171, 187, 213 Behavioral Symptoms, 8, 160 Benign, 160, 181, 194, 208 Bicuculline, 22, 160 Bilateral, 69, 70, 91, 96, 97, 108, 116, 160, 208 Bile, 123, 160, 178, 182, 188
Bile Acids, 160 Bile Acids and Salts, 160 Bile duct, 160 Biliary, 123, 160, 182 Bioavailability, 16, 160 Biochemical, 7, 9, 24, 29, 32, 36, 38, 113, 155, 157, 161, 209 Biological Markers, 16, 161 Biological therapy, 161, 180 Biological Transport, 161, 172 Biosynthesis, 161, 204, 209 Biotechnology, 63, 64, 126, 133, 135, 136, 137, 138, 161 Biotin, 110, 115, 160, 161 Bipolar Disorder, 39, 45, 66, 101, 161 Bladder, 161, 193, 195, 203, 216 Blood Coagulation, 161, 162, 214 Blood Platelets, 161, 209 Blood pressure, 157, 161, 165, 183, 193, 205 Blood vessel, 156, 161, 163, 165, 166, 169, 174, 181, 187, 189, 199, 210, 212, 213, 214, 217 Blood Volume, 27, 161 Blood-Brain Barrier, 161, 187 Blot, 44, 161 Bone Marrow, 161, 170, 179, 184, 189 Brachial, 162, 190 Brachial Plexus, 162, 190 Bradykinesia, 22, 54, 162 Bradykinin, 162, 196 Brain Stem, 4, 141, 162, 164, 195 Bronchial, 162, 182 Bruxism, 102, 162 Buccal, 162, 189 Butyric Acid, 17, 162 C Calcification, 68, 70, 72, 74, 79, 87, 90, 91, 96, 106, 136, 162 Calcitonin, 47, 162 Calcitonin Gene-Related Peptide, 47, 162 Calcium, 63, 86, 96, 162, 163, 167, 173, 183, 190, 192, 210 Calcium-Binding Proteins, 96, 163 Calibration, 42, 163 Cannabidiol, 163 Cannabinoids, 38, 163 Cannabinol, 163 Carbohydrate, 163, 180, 209 Carbon Dioxide, 163, 170, 178, 207 Carboxy, 37, 163 Carcinoembryonic Antigen, 82, 163 Carcinogenic, 163, 185, 197, 203
221
Carcinogens, 163, 197 Cardiac, 163, 169, 173, 175, 176, 198 Cardiopulmonary, 49, 163 Cardiopulmonary Bypass, 49, 163 Cardiovascular, 155, 163, 209, 211 Carotene, 163, 207 Carotenoids, 49, 163 Case report, 82, 83, 91, 100, 116, 163 Catecholamine, 157, 163, 172 Cat-Scratch Disease, 68, 163 Caudal, 164, 183, 197, 202 Caudate Nucleus, 9, 26, 160, 164, 169, 194, 197 Causal, 164, 175, 181 Cell Death, 24, 30, 35, 55, 158, 164, 194 Cell Differentiation, 164, 210 Cell Division, 136, 160, 164, 180, 191, 193, 201, 203 Cell membrane, 161, 164, 171, 178, 201 Cell proliferation, 96, 164, 210 Cell Respiration, 164, 192, 207 Cell Survival, 24, 164, 180 Cell Transplantation, 24, 61, 164 Central Nervous System, 13, 23, 24, 31, 48, 74, 86, 121, 153, 155, 159, 164, 166, 167, 171, 173, 178, 179, 180, 181, 187, 191, 192, 193, 196, 197, 202, 209 Cerebellar, 33, 40, 42, 43, 75, 110, 159, 164, 206, 216 Cerebellar Diseases, 159, 164, 216 Cerebral Cortex, 29, 52, 75, 81, 122, 141, 159, 164, 176, 177, 186, 194, 205 Cerebral hemispheres, 160, 162, 164, 165, 179, 187, 213 Cerebral Palsy, 49, 164 Cerebrospinal, 10, 122, 165, 166, 175, 210 Cerebrospinal fluid, 10, 122, 165, 166, 175, 210 Cerebrovascular, 47, 103, 160, 165, 214 Cerebrum, 72, 164, 165, 170, 213, 216 Ceroid, 165, 188 Cervical, 106, 162, 165, 190, 208 Cervix, 165 Character, 165, 170 Chelation, 5, 165 Chemokines, 165, 206 Chemoreceptor, 158, 165 Chemotactic Factors, 165, 168 Chin, 165, 191 Cholesterol, 160, 165 Choline, 32, 40, 51, 165 Cholinergic, 51, 116, 157, 165, 209
Chorea, 11, 49, 70, 76, 82, 85, 86, 99, 157, 165, 166 Choreatic Disorders, 165, 166 Chorioretinitis, 166, 207 Choroid, 166, 187, 207 Choroid Plexus, 166, 187 Chromatin, 158, 166, 189 Chromosome, 79, 87, 166, 182, 188 Chromosome Abnormalities, 166, 182 Chronic Fatigue Syndrome, 100, 166 Chronic renal, 166, 202 Cirrhosis, 32, 71, 123, 125, 166 CIS, 166, 207 Cleft Lip, 166, 182 Cleft Palate, 166, 182 Clinical Medicine, 166, 203 Clinical trial, 6, 8, 133, 166, 170, 173, 204, 206 Cloning, 38, 161, 166, 185 Clozapine, 43, 166 Coca, 167 Cocaine, 7, 167 Cofactor, 167, 204, 214 Cognition, 4, 16, 33, 72, 105, 167, 195 Collagen, 167, 177, 190, 202 Colloidal, 105, 154, 167 Coloboma, 167, 182 Colon, 136, 163, 167 Comatose, 103, 167 Common Variable Immunodeficiency, 86, 167 Compacta, 38, 167 Complement, 18, 61, 156, 167, 168, 179, 209 Complementary and alternative medicine, 113, 118, 168 Complementary medicine, 113, 168 Complete remission, 168, 207 Compress, 168, 182 Compulsions, 168, 197 Computational Biology, 133, 135, 168 Computed tomography, 107, 168 Computerized axial tomography, 168 Computerized tomography, 168 Concomitant, 44, 168 Cones, 168, 207 Confusion, 168, 195 Congestion, 158, 168 Conjunctiva, 168, 216 Connective Tissue, 162, 167, 169, 171, 177, 178, 189, 200 Consciousness, 72, 156, 169, 171, 172, 182
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Constipation, 158, 169 Constitutional, 169, 208 Constriction, 52, 169, 187, 217 Continuum, 46, 169 Contraindications, ii, 169 Contralateral, 84, 169, 191, 197, 206 Contrast Media, 106, 169 Contrast medium, 156, 169 Convulsions, 160, 169 Coordination, 42, 72, 164, 169, 193 Cor, 40, 169, 170 Cornea, 123, 169 Corpus, 61, 169, 179, 194, 209, 214, 218 Corpus Striatum, 169, 179, 194 Cortices, 58, 65, 170 Corticotropin-Releasing Hormone, 40, 170 Cranial, 107, 122, 164, 170, 181, 182, 197, 200, 216 Cranial Nerves, 122, 170 Cues, 27, 58, 88, 170 Curative, 170, 214 Cutaneous, 170, 189 Cyclic, 45, 170, 180, 196 Cyclopia, 170, 182 Cyclosporine, 61, 77, 170 Cyst, 91, 170 Cysteine, 165, 170, 206 Cytokine, 10, 35, 170 Cytoplasm, 158, 164, 170, 180, 189, 195, 208, 213 Cytoskeletal Proteins, 44, 170 Cytoskeleton, 170, 192 Cytotoxic, 170, 184, 210 D De novo, 30, 111, 170 Decarboxylation, 170, 182 Degenerative, 15, 16, 49, 91, 140, 141, 170, 179, 182, 189, 193, 208 Deletion, 88, 158, 170 Delirium, 157, 170 Delusions, 171, 181, 204 Dementia, 4, 8, 10, 28, 30, 48, 85, 86, 96, 153, 157, 158, 171, 195 Dendrites, 141, 171, 195, 196 Dendritic, 40, 171, 191 Dentate Gyrus, 171, 182 Deoxyglucose, 39, 171 Depolarization, 44, 51, 171, 210 Depressive Disorder, 66, 171, 188 Deprivation, 117, 171 Dermis, 171, 207 Desensitization, 171, 184
Dextroamphetamine, 155, 171, 192 Diagnostic procedure, 126, 171 Diastolic, 171, 183 Diffusion, 64, 161, 172 Digestion, 155, 160, 172, 188, 198, 212, 216 Dihydrotestosterone, 172, 206 Dilation, 162, 172, 217 Direct, iii, 14, 15, 28, 33, 34, 50, 63, 64, 80, 88, 90, 93, 166, 172, 207, 213 Discrete, 6, 7, 41, 64, 172 Discrimination, 117, 172 Disease Progression, 39, 54, 172, 217 Disparity, 8, 172 Dissociation, 114, 154, 172, 186 Dissociative Disorders, 172 Distal, 82, 172, 173, 200, 204 Dominance, 172, 187 Dopa, 99, 172, 187 Dopamine Agonists, 44, 172 Dorsal, 18, 44, 51, 54, 58, 76, 172, 175, 202, 209, 211 Dorsum, 172, 173 Double-blind, 16, 27, 173 Drive, ii, vi, 17, 23, 109, 173 Drug Interactions, 173 Duodenum, 160, 173, 198, 212 Dura mater, 173, 191, 198 Dyskinesia, 99, 158, 173 Dysphoric, 171, 173 Dysplasia, 72, 137, 173 Dystonia, 11, 13, 20, 25, 37, 39, 59, 69, 70, 77, 82, 92, 106, 158, 173 Dystrophy, 136, 173 E Ectopic, 54, 173 Edema, 173, 182 Effector, 153, 167, 173 Efferent, 50, 170, 173, 186, 193, 209 Efferent Pathways, 50, 173 Efficacy, 9, 16, 27, 30, 35, 173 Electrode, 7, 11, 116, 173 Electrolytes, 160, 173 Electromyography, 123, 173 Electrons, 157, 160, 173, 186, 190, 198, 205 Electroretinogram, 36, 174 Elementary Particles, 173, 174, 190, 204 Emaciation, 153, 174 Emboli, 76, 77, 174 Embolization, 76, 77, 174 Embolus, 174, 185 Embryo, 164, 174, 185, 203 Emesis, 158, 174
223
Emetic, 158, 174 Emulsion, 159, 174, 178 Encephalitis, 28, 77, 174 Encephalitis, Viral, 174 Encephalopathy, 4, 32, 65, 174 Endogenous, 162, 172, 174 Endorphins, 174, 196 Endothelium, 174, 175, 196 Endothelium-derived, 175, 196 Endotoxin, 55, 175 End-stage renal, 166, 175, 202 Enkephalin, 22, 175 Entopeduncular Nucleus, 17, 33, 175 Entorhinal Cortex, 23, 175, 182 Environmental Exposure, 49, 161, 175, 197 Environmental Health, 132, 134, 175 Enzymatic, 162, 163, 168, 175, 182, 207 Enzyme, 29, 51, 161, 173, 175, 179, 180, 189, 193, 200, 201, 204, 206, 210, 212, 214, 218 Ependymal, 175, 179 Ependymal tumors, 175, 179 Epidemic, 8, 175, 211 Epidemiologic Studies, 161, 175 Epinephrine, 154, 172, 175, 196, 216 Epithalamus, 175, 188 Epithelial, 161, 175, 176 Epithelial Cells, 176 Epithelium, 54, 174, 176, 187 Erythrocyte Volume, 161, 176 Erythrocytes, 156, 162, 176, 181, 206, 209 Essential Tremor, 136, 176 Estrogens, 176, 180 Eukaryotic Cells, 170, 176, 184, 198, 216 Evoke, 176, 212 Excitability, 51, 57, 176 Excitation, 38, 51, 165, 176, 196 Excitatory, 17, 20, 23, 36, 38, 45, 176, 179, 180 Excitotoxicity, 73, 176 Exhaustion, 156, 176 Exocrine, 176, 198 Exogenous, 47, 174, 176 Expiration, 176, 202, 207 Exploratory Behavior, 15, 176 Extracellular, 12, 20, 22, 47, 79, 159, 169, 176, 177, 190, 192, 195 Extracellular Matrix, 169, 176, 177, 190 Extracellular Matrix Proteins, 176, 190 Extracellular Space, 176, 177, 192 Extraocular, 72, 177
Extrapyramidal, 25, 36, 49, 50, 51, 154, 158, 172, 177 Extremity, 162, 177, 190 Eye Movements, 25, 177 F Facial, 31, 88, 177, 182, 211 Facial Expression, 31, 177 Family Planning, 133, 177 Fat, 160, 162, 163, 169, 174, 177, 188, 194 Fatigue, 79, 166, 177 Feces, 163, 169, 177, 212 Femoral, 163, 177 Femoral Artery, 163, 177 Fetoprotein, 177 Fetus, 155, 177, 203, 216 Fibrin, 161, 177, 201, 214 Fibroblasts, 24, 177 Fibrosis, 72, 137, 177, 208 Fissure, 166, 167, 171, 177, 203 Fixation, 177, 208, 209 Flexor, 178, 211 Fluoxetine, 41, 178 Foramen, 165, 178, 187 Forearm, 161, 178, 190 Fossa, 164, 178 Free Radicals, 157, 172, 178 Frontal Lobe, 3, 4, 5, 32, 93, 178, 193, 203 Functional magnetic resonance imaging, 25, 27, 42, 57, 65, 81, 178 Fungicide, 178, 190 G Gait, 26, 58, 81, 164, 178 Gallbladder, 160, 178 Gap Junctions, 178 Gas, 155, 163, 172, 178, 183, 196, 202, 217 Gas exchange, 178, 202, 217 Gasoline, 56, 178 Gastric, 178, 182 Gastrointestinal, 123, 162, 163, 175, 178, 209, 211, 212 Gastrointestinal tract, 163, 178, 209 Gene Expression, 28, 29, 47, 59, 62, 78, 137, 178, 179 Gene Therapy, 23, 55, 179 Genetic Engineering, 161, 166, 179 Genetic testing, 140, 141, 179 Genetics, 36, 54, 79, 87, 91, 123, 172, 179 Genotype, 36, 179, 200 Germinoma, 67, 83, 85, 116, 179 Gestation, 167, 179, 200 Gestures, 31, 179
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Gland, 179, 189, 198, 201, 203, 209, 212, 214 Glial tumors, 94, 179 Glioblastoma, 179 Glioblastoma multiforme, 179 Glioma, 91, 179 Gliosis, 40, 56, 179 Globus Pallidus, 9, 15, 21, 22, 26, 30, 38, 42, 49, 54, 56, 106, 119, 160, 169, 175, 179, 205 Glucose, 77, 136, 171, 179, 181, 185 Glutamate, 6, 12, 17, 30, 32, 44, 53, 74, 78, 84, 90, 93, 95, 105, 176, 179, 180, 191 Glutamic Acid, 37, 180, 196 Glutamine, 32, 180 Glutathione Peroxidase, 66, 180 Glycerol, 162, 180, 201 Glycine, 160, 180, 196, 209 Glycoprotein, 30, 163, 180, 214 Gonadotropin, 82, 180 Governing Board, 180, 202 Gp120, 35, 180 Grade, 94, 179, 180 Graft, 8, 61, 180 Graft Survival, 9, 180 Grafting, 8, 180, 184 Gram-negative, 163, 180 Granulocytes, 180, 210, 218 Growth factors, 28, 180, 192 Guanine, 29, 180 Guanosine Triphosphate, 24, 180 Guanylate Cyclase, 180, 196 Gyrus Cinguli, 181, 188 H Habitual, 60, 165, 181 Haematoma, 94, 181 Hallucinogens, 181, 205 Haloperidol, 16, 22, 43, 181 Handedness, 31, 181 Headache, 181, 217 Hematoma, 181, 182 Hemiatrophy, 85, 181 Hemicrania, 181, 217 Hemiparesis, 84, 181 Hemoglobin, 156, 176, 181 Hemoglobinopathies, 179, 181 Hemoglobinuria, 136, 181 Hemolysis, 123, 181 Hemolytic, 84, 85, 123, 181 Hemorrhage, 76, 87, 181, 212 Hemorrhagic stroke, 93, 181 Hemostasis, 182, 209
Hepatic, 5, 32, 70, 71, 86, 123, 155, 171, 182, 188 Hepatic Encephalopathy, 32, 70, 71, 182 Hepatitis, 123, 182 Hepatobiliary, 123, 182 Hepatocyte, 123, 182 Hereditary, 86, 98, 140, 141, 166, 182, 193, 194, 200, 208 Heredity, 178, 179, 182 Heterogeneity, 53, 59, 154, 182 Heterozygotes, 103, 172, 182 Hippocampus, 39, 40, 45, 52, 58, 72, 73, 95, 141, 171, 182, 188, 195, 209, 212 Histamine, 74, 156, 157, 182 Histidine, 182 Histology, 182, 195 Histone Deacetylase, 16, 182 Histones, 166, 182 Holoprosencephaly, 96, 182 Homeobox, 29, 183 Homogeneous, 169, 183 Homologous, 155, 179, 182, 183, 209, 213 Hormonal, 159, 183 Hormone, 161, 162, 175, 183, 186, 210, 214 Hybrid, 183 Hybridization, 28, 52, 183 Hydrogen, 153, 155, 160, 163, 176, 180, 183, 188, 193, 197, 198, 200, 204, 212 Hydrogen Peroxide, 180, 183, 188, 212 Hydrolysis, 57, 183, 201, 202, 204 Hypercalcemia, 16, 183 Hyperglycemia, 70, 183 Hyperreflexia, 4, 183 Hypersensitivity, 155, 171, 183, 209 Hypertension, 103, 181, 183 Hypertrophy, 169, 183, 216 Hypogammaglobulinemia, 167, 183 Hypokinesia, 183, 199 Hypoplasia, 40, 183 Hypotension, 158, 169, 183 Hypothalamic, 40, 87, 183 Hypothalamus, 41, 48, 122, 141, 159, 170, 175, 183, 188, 201, 209, 214 Hypoxanthine, 29, 184 I Idiopathic, 39, 55, 59, 65, 77, 79, 87, 105, 184 Imidazole, 161, 182, 184 Immune response, 157, 159, 184, 209, 212, 218 Immune system, 53, 159, 161, 184, 189, 194, 216, 218
225
Immunity, 153, 184 Immunization, 184, 209 Immunodeficiency, 10, 30, 35, 53, 136, 153, 167, 183, 184 Immunodeficiency syndrome, 167, 184 Immunohistochemistry, 28, 36, 52, 184 Immunosuppression, 53, 61, 184, 189, 197 Immunosuppressive, 184 Immunosuppressive Agents, 184 Impairment, 5, 8, 34, 51, 54, 159, 171, 173, 184, 191, 204 Implantation, 9, 11, 17, 184 In situ, 6, 28, 37, 40, 44, 50, 56, 78, 114, 184 In Situ Hybridization, 6, 37, 40, 44, 50, 78, 184 In vitro, 20, 30, 35, 45, 47, 52, 54, 55, 90, 115, 179, 184 In vivo, 7, 16, 20, 23, 30, 31, 35, 45, 46, 52, 54, 55, 56, 61, 62, 179, 184, 189, 192 Incision, 184, 186 Incubation, 184, 185, 187 Incubation period, 185, 187 Induction, 13, 51, 54, 157, 185 Infarction, 70, 71, 158, 182, 185 Inflammation, 48, 51, 55, 155, 166, 174, 177, 182, 185, 191, 195, 196, 198, 202, 207, 208, 217 Infusion, 16, 25, 39, 185 Initiation, 14, 29, 43, 46, 58, 90, 185 Innervation, 21, 30, 38, 52, 75, 78, 104, 162, 185, 190 Inositol, 32, 185, 191 Inotropic, 172, 185 Inpatients, 46, 185 Insecticides, 185, 200 Insertional, 6, 185 Insight, 18, 33, 36, 37, 48, 54, 59, 185 Insulator, 141, 185, 194 Intermediate Filaments, 185, 195 Intermittent, 16, 24, 186, 189 Internal Capsule, 90, 170, 175, 186 Interneurons, 47, 116, 186 Interstitial, 103, 177, 186 Intestinal, 163, 186, 190 Intestines, 177, 178, 186, 209 Intoxication, 66, 171, 186 Intracellular, 23, 37, 51, 90, 101, 185, 186, 191, 196, 206, 210 Intramuscular, 186, 198 Intravenous, 108, 185, 186, 199 Intrinsic, 20, 154, 186
Invasive, 10, 50, 62, 82, 85, 103, 184, 186, 189 Involuntary, 23, 32, 49, 60, 104, 140, 160, 165, 176, 186, 207, 211 Iodine, 92, 186 Ion Channels, 159, 186, 195 Ion Exchange, 186 Ionization, 186 Ionizing, 175, 186 Ions, 160, 163, 172, 173, 183, 186 Iontophoresis, 44, 186 Ipsilateral, 84, 106, 186, 191, 206 Iris, 169, 187, 205 Ischemia, 49, 114, 159, 181, 187 K Kb, 132, 187 Kidney Disease, 132, 137, 187 Kinetics, 36, 187 L Labile, 167, 187 Laryngeal, 123, 187 Larynx, 187 Latent, 74, 187 Lateral Ventricles, 6, 187, 209, 214 Laterality, 31, 92, 187 Lentivirus, 55, 187 Lesion, 7, 15, 18, 24, 44, 70, 78, 93, 103, 106, 179, 187, 188, 213 Leukemia, 136, 179, 187 Levo, 172, 187 Levodopa, 25, 26, 30, 38, 106, 172, 187 Ligament, 187, 203 Limbic, 19, 23, 39, 50, 60, 122, 156, 181, 188, 203 Limbic System, 122, 156, 181, 188, 203 Linkage, 37, 45, 57, 59, 188 Lipid, 36, 165, 180, 188, 194, 198 Lipid Peroxidation, 36, 188, 198 Lipofuscin, 36, 165, 188 Lithium, 157, 188 Liver, 5, 32, 70, 90, 93, 122, 123, 154, 155, 160, 161, 166, 174, 177, 178, 182, 188, 202 Liver cancer, 155, 188 Liver Cirrhosis, 70, 188 Liver Transplantation, 5, 188 Lobe, 4, 5, 19, 188 Lobule, 4, 188 Localization, 93, 105, 107, 184, 188 Localized, 13, 23, 39, 40, 91, 115, 153, 178, 181, 185, 188, 201 Locomotion, 6, 15, 102, 188, 201 Locomotor, 7, 15, 22, 57, 188
226
Basal Ganglia
Longitudinal study, 39, 188 Long-Term Care, 18, 189 Loop, 19, 59, 80, 189 Luciferase, 47, 51, 189 Lupus, 74, 86, 189 Lycopene, 49, 189 Lymph, 165, 175, 189, 207, 208 Lymph node, 165, 189, 207, 208 Lymphatic, 175, 185, 189, 208 Lymphatic system, 189, 208 Lymphocyte Count, 153, 189 Lymphocyte Depletion, 184, 189 Lymphocytes, 153, 157, 184, 189, 218 Lymphoid, 157, 189 Lymphoma, 136, 189 M Macroglia, 189, 192, 195 Macrophage, 28, 189 Macula, 189 Macula Lutea, 189 Macular Degeneration, 37, 189 Magnetic Resonance Imaging, 3, 31, 52, 81, 82, 95, 97, 100, 189, 190 Magnetic Resonance Spectroscopy, 16, 40, 76, 93, 94, 100, 105, 111, 190 Maintenance therapy, 5, 190 Malabsorption, 136, 190 Malignancy, 16, 190 Malignant, 136, 153, 179, 188, 190, 194, 213 Malnutrition, 155, 159, 190, 194 Mammogram, 162, 190, 192 Maneb, 55, 190 Mania, 40, 46, 190 Manic, 157, 161, 188, 190, 204 Manic-depressive psychosis, 190, 204 Manifest, 37, 60, 190 Mastication, 190, 216 Matrix metalloproteinase, 114, 190 Mechanical ventilation, 53, 190, 202 Medial, 4, 13, 16, 18, 36, 58, 74, 97, 166, 175, 179, 181, 190, 197, 209 Median Nerve, 79, 88, 190 Mediate, 47, 172, 190, 206 Mediator, 7, 22, 51, 172, 190, 209 MEDLINE, 133, 135, 137, 190 Medullary, 191, 205 Meiosis, 191, 213 Melanin, 187, 191, 200, 216 Melanocytes, 191 Melanoma, 136, 191 Memory, 18, 19, 25, 26, 33, 41, 46, 74, 89, 92, 99, 115, 120, 141, 171, 191
Meninges, 164, 173, 191 Meningitis, 69, 91, 191 Mental Disorders, 23, 183, 191, 204 Mental Health, iv, 5, 18, 27, 132, 134, 191 Mental Processes, 172, 191, 204 Mental Retardation, 107, 136, 138, 182, 191 Mentors, 18, 191 Mesencephalic, 55, 191, 206 Mesolimbic, 157, 191, 217 Meta-Analysis, 70, 191 Metabolite, 32, 94, 191, 205 Metabotropic, 74, 90, 93, 95, 191 Metastasis, 190, 191, 194 Methamphetamine, 18, 35, 50, 191 Methylprednisolone, 61, 192 Microbe, 192, 215 Microbiology, 153, 159, 192 Microcalcifications, 162, 192 Microcirculation, 188, 192 Microdialysis, 7, 22, 47, 62, 93, 192 Microglia, 55, 159, 192, 193, 195 Microorganism, 167, 192, 218 Microscopy, 47, 90, 192 Microtubule-Associated Proteins, 192, 195 Microtubules, 185, 192, 194 Micturition, 3, 192 Migration, 166, 192, 195, 206 Mineralization, 76, 95, 108, 192 Mitochondria, 192, 198 Mitochondrial Swelling, 192, 194 Mitosis, 158, 193 Mobility, 54, 193 Modeling, 20, 37, 42, 52, 60, 63, 193 Modification, 179, 193, 205 Modulator, 7, 193 Monitor, 10, 163, 193, 196 Monoamine, 21, 35, 116, 155, 157, 171, 193 Monoclonal, 61, 193, 205 Monoclonal antibodies, 61, 193 Morphine, 158, 193 Morphological, 24, 43, 61, 114, 174, 191, 193 Morphology, 19, 43, 193 Motility, 193, 209 Motor Activity, 20, 21, 169, 193 Motor Cortex, 21, 73, 92, 111, 193, 206 Motor nerve, 193, 197 Motor Skills, 39, 193 Mucosa, 189, 193 Multiple sclerosis, 87, 193 Muscle Contraction, 13, 49, 194 Muscle Fibers, 123, 194
227
Muscular Atrophy, 136, 194 Myelin, 6, 194, 195 Myopathy, 91, 194 Myosin, 194 Myotonic Dystrophy, 136, 194 N Nausea, 157, 158, 194 Necrosis, 66, 87, 106, 158, 179, 185, 194 Neocortex, 194, 195 Neonatal, 45, 115, 194 Neoplasia, 136, 194 Neoplasms, 153, 163, 194, 214 Neostriatum, 164, 169, 194, 205 Nephropathy, 187, 194 Networks, 38, 42, 65, 105, 194 Neurodegenerative Diseases, 24, 56, 160, 194 Neurofibrillary Tangles, 74, 194 Neurofilaments, 194, 195 Neurogenic, 47, 195 Neurogenic Inflammation, 47, 195 Neuroglia, 179, 189, 195 Neuroleptic, 68, 154, 157, 166, 195 Neurologic, 5, 13, 32, 49, 156, 179, 195 Neurologic Manifestations, 5, 195 Neuromuscular, 123, 153, 195 Neuromuscular Junction, 123, 153, 195 Neuropathy, 51, 195, 200 Neuropeptide, 47, 50, 162, 170, 195 Neuropharmacology, 25, 84, 195 Neurophysiology, 46, 47, 53, 65, 87, 99, 108, 114, 116, 171, 195 Neuropil, 40, 195 Neuropsychological Tests, 32, 196 Neuropsychology, 25, 89, 196 Neuroretinitis, 196, 208 Neurosurgical Procedures, 11, 14, 196 Neurotoxic, 36, 50, 196 Neurotoxicity, 31, 35, 36, 50, 53, 55, 56, 77, 196 Neurotoxin, 8, 196 Neurotransmitter, 7, 22, 29, 38, 51, 56, 62, 90, 93, 153, 154, 162, 172, 179, 180, 182, 186, 196, 210, 212 Night Blindness, 196, 208 Nitric Oxide, 28, 47, 55, 196 Nitrogen, 155, 176, 178, 180, 196, 198, 216 Norepinephrine, 154, 172, 196 Nuclear, 7, 10, 75, 77, 87, 92, 113, 160, 173, 176, 179, 186, 188, 194, 196, 214 Nucleic acid, 183, 184, 196 Nucleic Acid Hybridization, 183, 197
Nucleus, 6, 11, 12, 14, 15, 17, 21, 23, 24, 26, 30, 33, 38, 40, 41, 42, 44, 48, 49, 54, 58, 62, 63, 114, 119, 158, 166, 169, 170, 174, 175, 176, 179, 185, 189, 191, 197, 203, 204, 205, 206, 209, 211, 214, 217 Nucleus Accumbens, 6, 23, 48, 114, 197, 217 O Obsessive-Compulsive Disorder, 101, 197 Occipital Lobe, 4, 197 Ocular, 197, 208 Oculomotor, 25, 191, 197 Oncogene, 136, 197 Oncogenic, 187, 197 On-line, 35, 59, 151, 197 Open Reading Frames, 187, 197 Opiate, 175, 193, 197 Opportunistic Infections, 153, 197 Opsin, 197, 207, 208 Optic Chiasm, 183, 197 Optic Nerve, 196, 197, 198, 207 Orbit, 197 Orbital, 4, 197 Organelles, 44, 170, 191, 198, 201 Orthostatic, 158, 198 Osteoclasts, 162, 198 Ovaries, 198, 210, 213 Overdosage, 106, 198 Oxidation, 153, 157, 180, 188, 198 Oxidative Stress, 9, 24, 198 Oxygen Consumption, 198, 207 Oxygenation, 181, 198 Oxygenator, 163, 198 P Pacemaker, 46, 198 Pachymeningitis, 191, 198 Palliative, 198, 214 Pancreas, 161, 198 Pancreatic, 90, 136, 198 Pancreatic cancer, 136, 198 Pancreatic Insufficiency, 90, 198 Paralysis, 154, 181, 191, 198 Parenteral, 86, 198, 199 Parenteral Nutrition, 86, 199 Parietal, 3, 16, 32, 141, 199 Parietal Lobe, 32, 199 Parkinsonism, 12, 15, 22, 56, 59, 79, 99, 158, 187, 199 Paroxysmal, 136, 199, 217 Partial remission, 199, 207 Patch, 45, 199 Pathologic, 158, 183, 199
228
Basal Ganglia
Pathologic Processes, 158, 199 Pathologies, 52, 199 Pathologist, 140, 199 Pathophysiology, 6, 10, 13, 30, 32, 36, 43, 46, 49, 53, 98, 102, 123, 124, 199 Patient Education, 140, 146, 148, 151, 199 Pedigree, 59, 199 Peduncle, 175, 199, 206 Pelvic, 199, 203 Penicillamine, 5, 199 Penicillin, 156, 199, 216 Peptide, 162, 199, 202, 204 Perception, 43, 46, 67, 181, 199 Perfusion, 21, 57, 99, 113, 199 Pergolide, 24, 199 Perinatal, 93, 101, 200 Peripheral Nerves, 123, 200, 211 Peripheral Nervous System, 121, 194, 196, 200, 212 Peripheral Neuropathy, 51, 200 Perivascular, 162, 192, 200 Periventricular Leukomalacia, 100, 200 Peroxidase, 115, 188, 200 Peroxide, 200 Pesticides, 49, 185, 200 Petroleum, 178, 200 PH, 52, 86, 106, 200 Phagocytosis, 192, 200 Pharmacodynamic, 15, 200 Pharmacokinetic, 15, 200 Pharmacologic, 49, 156, 200, 215 Phenotype, 6, 7, 29, 36, 161, 200 Phenyl, 55, 200 Phenylalanine, 200, 216 Phenylbutyrate, 16, 200 Phobias, 48, 200 Phonophoresis, 186, 201 Phospholipases, 201, 210 Phospholipids, 177, 185, 201 Phosphorous, 94, 201 Phosphorus, 90, 162, 201 Phosphorylates, 29, 201 Photoreceptor, 36, 201, 208 Physical Examination, 123, 201 Physiologic, 53, 154, 161, 172, 183, 201, 206, 216 Physiology, 7, 10, 15, 34, 38, 45, 52, 54, 62, 64, 69, 98, 121, 123, 160, 161, 195, 201 Pigment, 123, 165, 188, 189, 191, 201, 207 Pituitary Gland, 170, 201 Plants, 155, 160, 163, 165, 167, 179, 193, 196, 201, 215
Plasma, 76, 154, 157, 161, 162, 164, 181, 182, 201, 209, 217 Plasma cells, 157, 201 Plasma Volume, 161, 201 Plasmin, 201, 214 Plasticity, 24, 35, 37, 41, 61, 117, 201 Plastids, 198, 201 Platelet Activation, 202, 210 Platelet Aggregation, 156, 196, 202 Platelets, 196, 202 Pleomorphic, 197, 202 Pneumonia, 169, 202 Poisoning, 158, 171, 186, 194, 202 Polycystic, 137, 202 Polymorphism, 49, 202 Polypeptide, 155, 167, 183, 201, 202, 218 Pons, 4, 162, 202, 207 Pontine, 78, 202 Portal Vein, 202 Portosystemic Shunt, 85, 202 Positive End-Expiratory Pressure, 53, 202 Posterior, 156, 159, 164, 166, 172, 173, 175, 186, 187, 197, 198, 202 Postoperative, 86, 202 Postsynaptic, 7, 35, 47, 202, 210 Post-traumatic, 106, 193, 202 Postural, 27, 102, 202 Potentiation, 202, 210 Practice Guidelines, 134, 202 Preclinical, 30, 203 Precursor, 5, 25, 50, 165, 172, 173, 174, 175, 187, 196, 200, 203, 216 Prednisolone, 192, 203 Prefrontal Cortex, 18, 23, 25, 26, 33, 39, 40, 45, 60, 72, 73, 203 Prenatal, 36, 174, 203 Prenatal Diagnosis, 36, 203 Preoperative, 11, 203 Presynaptic, 7, 51, 196, 203, 213 Primitive neuroectodermal tumors, 179, 203 Probe, 19, 27, 35, 192, 203 Procaine, 154, 203 Progression, 24, 39, 56, 156, 203 Progressive, 5, 6, 36, 40, 48, 53, 54, 105, 124, 164, 166, 171, 181, 194, 202, 203, 208 Projection, 17, 19, 29, 52, 186, 196, 197, 203, 206, 217 Promoter, 13, 47, 203 Prophase, 203, 213 Prosencephalon, 182, 203, 213 Prospective study, 87, 188, 203
229
Prostate, 136, 203 Protease, 10, 204, 214 Protease Inhibitors, 10, 204 Protein C, 13, 154, 155, 204 Protein S, 137, 161, 204, 208 Proteolytic, 167, 201, 204, 214 Protocol, 7, 46, 204 Protons, 183, 186, 190, 204, 205 Proximal, 172, 203, 204, 209 Pruritus, 158, 204 Psychiatric, 4, 11, 14, 29, 30, 45, 46, 48, 79, 94, 108, 161, 191, 204, 210 Psychic, 191, 204, 209 Psychology, 6, 11, 22, 38, 44, 59, 60, 168, 172, 196, 204 Psychopathology, 46, 204 Psychophysiology, 196, 204 Psychosis, 4, 15, 157, 158, 204 Psychotomimetic, 155, 171, 204 Psychotropic, 45, 204, 205 Psychotropic Drugs, 45, 205 Public Policy, 133, 205 Publishing, 63, 123, 205 Pulmonary, 52, 161, 169, 205, 217 Pulmonary hypertension, 169, 205 Pulse, 57, 174, 193, 205 Punishment, 34, 205 Pupil, 169, 172, 205 Putamen, 9, 40, 49, 61, 160, 169, 194, 205 Pyramidal Tracts, 177, 205 Q Quality of Life, 11, 140, 205 Quinolinic, 28, 205 Quinolinic Acid, 28, 205 R Race, 49, 172, 192, 205 Racemic, 172, 205 Radiation, 153, 159, 174, 175, 178, 184, 186, 205, 218 Radiation therapy, 153, 205 Radioactive, 159, 183, 184, 186, 193, 196, 197, 205 Radiography, 156, 169, 206 Radiological, 4, 206 Radiology, 31, 51, 69, 94, 106, 108, 110, 206 Randomized, 16, 27, 173, 206 Raphe Nuclei, 40, 206 Reaction Time, 34, 114, 206 Reactive Oxygen Species, 35, 50, 206 Reagent, 189, 206 Reality Testing, 204, 206 Receptors, Chemokine, 28, 206
Receptors, Serotonin, 206, 209 Recombinant, 94, 206, 217 Recombination, 179, 206 Rectum, 158, 167, 178, 204, 206 Recurrence, 161, 190, 206 Red blood cells, 123, 176, 181, 206 Red Nucleus, 33, 42, 159, 206, 217 Reductase, 29, 206 Refer, 1, 162, 167, 174, 177, 186, 188, 189, 195, 204, 207, 209, 215, 217 Reflex, 141, 177, 207 Refraction, 207, 211 Regimen, 16, 36, 173, 207 Regional lymph node, 163, 207 Remission, 41, 161, 190, 206, 207 Research Support, 46, 207 Resected, 82, 207 Respiration, 141, 163, 165, 193, 207 Respirator, 190, 207 Respiratory distress syndrome, 52, 207 Respiratory Physiology, 207, 217 Reticular, 122, 207 Reticular Formation, 122, 207 Retina, 36, 166, 168, 189, 195, 196, 197, 207, 208, 218 Retinal, 36, 172, 197, 207, 208 Retinal pigment epithelium, 36, 207 Retinitis, 36, 207, 208 Retinitis Pigmentosa, 36, 208 Retinoblastoma, 136, 208 Retinol, 207, 208 Retinopathy, 36, 208 Retroviral vector, 179, 208 Rhodopsin, 197, 207, 208 Ribose, 154, 208 Ribosome, 208, 215 Rigidity, 48, 99, 199, 201, 208 Risk factor, 175, 203, 208 Risperidone, 66, 208 Rod, 36, 160, 201, 208 Rodenticides, 200, 208 Rotenone, 21, 113, 208 Rubella, 79, 208 S Saccades, 26, 63, 208 Salivary, 198, 208 Schizophrenia, 6, 11, 15, 18, 23, 34, 43, 45, 46, 66, 81, 94, 95, 158, 208, 217 Sclerosis, 136, 193, 208 Screening, 36, 59, 166, 209 Secretion, 40, 182, 192, 198, 209, 216 Secretory, 209
230
Basal Ganglia
Segmentation, 182, 209 Seizures, 95, 102, 136, 171, 179, 182, 199, 209 Semen, 203, 209 Senescence, 9, 37, 209 Senile, 158, 209 Sensitization, 7, 209 Septal, 40, 114, 188, 209 Septal Nuclei, 188, 209 Septum, 187, 209 Septum Pellucidum, 187, 209 Sequence Analysis, 36, 209 Sequencing, 43, 209 Serine, 209, 214 Serotonin, 11, 22, 41, 57, 141, 157, 166, 178, 196, 206, 208, 209, 212, 216 Serum, 32, 47, 49, 86, 154, 156, 167, 180, 189, 209 Sex Characteristics, 154, 176, 210, 214 Sex Determination, 137, 210 Shock, 37, 210, 216 Shunt, 76, 210 Side effect, 16, 32, 49, 154, 158, 161, 210, 215 Signal Transduction, 57, 185, 210 Signs and Symptoms, 30, 195, 207, 210 Skeletal, 86, 210, 211 Skeleton, 153, 210 Skull, 197, 210, 213 Sleep Deprivation, 57, 210 Smooth muscle, 156, 182, 193, 210, 211, 212 Social Behavior, 59, 210 Social Environment, 205, 210 Solitary Nucleus, 159, 210 Solvent, 87, 180, 211 Somatic, 154, 170, 188, 191, 193, 200, 203, 211 Songbirds, 34, 41, 59, 211 Spasm, 191, 211 Specialist, 110, 142, 172, 211 Species, 35, 44, 50, 53, 164, 175, 183, 187, 191, 192, 193, 205, 206, 210, 211, 212, 216, 217, 218 Specificity, 13, 28, 154, 211 Spectrum, 46, 192, 211 Speech Perception, 42, 211 Sperm, 166, 211, 214 Sphincter, 4, 187, 211 Spinal Nerves, 200, 211 Spirometry, 52, 211 Sporadic, 194, 208, 211
Steady state, 16, 211 Stereotactic, 30, 76, 90, 94, 95, 103, 211 Stimulant, 13, 18, 155, 171, 182, 191, 212, 216 Stimulus, 14, 27, 46, 51, 55, 62, 173, 176, 185, 186, 195, 201, 205, 206, 207, 212, 214 Stomach, 178, 183, 186, 194, 212 Stool, 167, 212 Stress, 37, 123, 159, 163, 194, 198, 212 Stria, 29, 40, 209, 212 Stroke, 3, 93, 103, 110, 125, 132, 181, 212 Subacute, 4, 16, 95, 103, 185, 212 Subclinical, 185, 209, 212 Subcutaneous, 173, 181, 198, 212 Subiculum, 182, 212 Subliminal, 104, 212 Subspecies, 211, 212 Substance P, 191, 209, 212 Sumatriptan, 47, 212 Superoxide, 66, 212 Superoxide Dismutase, 66, 212 Support group, 141, 212 Suppression, 22, 55, 68, 212 Supratentorial, 99, 212 Sympathetic Nervous System, 159, 212, 213 Sympathomimetic, 155, 171, 172, 175, 191, 196, 213 Symphysis, 165, 203, 213 Symptomatic, 55, 101, 156, 213 Symptomatology, 4, 18, 22, 213 Synapse, 84, 154, 195, 203, 213, 216 Synapsis, 213 Synaptic, 20, 40, 41, 43, 44, 51, 115, 195, 196, 210, 213 Synaptic Vesicles, 213 Synergistic, 30, 53, 64, 213 Syrinx, 211, 213 Systemic, 10, 12, 22, 30, 76, 158, 161, 171, 175, 185, 195, 203, 205, 213, 216 Systolic, 183, 213 T Tardive, 158, 213 Telangiectasia, 86, 137, 213 Telencephalon, 54, 160, 164, 203, 213 Temporal, 3, 8, 13, 19, 27, 34, 38, 49, 54, 58, 74, 87, 89, 97, 117, 141, 156, 182, 189, 213 Temporal Lobe, 87, 89, 97, 141, 156, 213 Teratoma, 116, 213 Terminalis, 40, 209, 213, 214 Testicles, 213, 214 Testosterone, 206, 214
231
Tetrahydrocannabinol, 163, 214 Thalamic, 13, 18, 22, 48, 64, 67, 75, 77, 78, 99, 105, 159, 175, 214 Thalamic Diseases, 159, 214 Thalamic Nuclei, 78, 175, 214 Therapeutics, 51, 74, 95, 110, 214 Thermal, 172, 214 Third Ventricle, 175, 183, 187, 214 Thoracic, 162, 189, 190, 214 Threshold, 21, 56, 176, 183, 212, 214 Thrombin, 177, 202, 204, 214 Thrombomodulin, 204, 214 Thrombosis, 204, 212, 214 Thyroid, 162, 186, 214, 216 Tissue Plasminogen Activator, 94, 214 Tolerance, 153, 215 Tomography, 25, 52, 77, 86, 97, 114, 190, 215 Tone, 100, 102, 215 Tonic, 17, 215 Tonicity, 173, 181, 215 Tonus, 215 Tooth Preparation, 153, 215 Torsion, 11, 37, 39, 185, 215 Toxic, iv, 28, 49, 175, 184, 195, 215 Toxicity, 35, 56, 122, 173, 215 Toxicology, 35, 50, 134, 215 Toxin, 21, 175, 215 Trace element, 102, 122, 215 Tranquilizing Agents, 205, 215 Transduction, 210, 215 Transfection, 161, 179, 215 Translation, 29, 62, 215 Translational, 44, 215 Transmitter, 67, 90, 153, 159, 172, 186, 190, 195, 196, 213, 215 Transplantation, 5, 8, 23, 61, 62, 125, 166, 184, 189, 216 Trauma, 117, 160, 171, 181, 194, 214, 216 Tremor, 22, 32, 54, 99, 191, 199, 216 Tricuspid Atresia, 169, 216 Trigeminal, 47, 216 Trigger zone, 158, 216 Trophic, 9, 10, 216 Tryptophan, 167, 205, 209, 216 Tubercle, 197, 216 Tuberculosis, 189, 216 Tuberous Sclerosis, 137, 216 Tyrosine, 9, 13, 24, 29, 172, 216 U Ubiquitin, 195, 216 Urethra, 203, 216
Urinary, 3, 214, 216 Urine, 161, 181, 192, 216 Urodynamics, 4, 216 Uterus, 165, 169, 198, 216 V Vaccine, 204, 216 Vacuoles, 198, 216 Valine, 199, 216 Vascular, 47, 117, 166, 171, 175, 185, 188, 192, 195, 196, 217 Vascular Headaches, 47, 217 Vasculitis, 70, 217 Vasodilator, 162, 172, 182, 217 Vector, 37, 55, 185, 215, 217 Vein, 158, 186, 196, 202, 217 Venous, 158, 204, 216, 217 Venter, 217 Ventilation, 52, 217 Ventral, 18, 40, 43, 54, 58, 183, 197, 202, 211, 217 Ventral Tegmental Area, 40, 43, 217 Ventricle, 156, 159, 164, 169, 182, 187, 197, 205, 213, 214, 216, 217 Ventricular, 107, 169, 216, 217 Vertebrae, 211, 217 Vesicular, 51, 217 Vestibular, 122, 217 Vestibule, 217 Veterinary Medicine, 52, 133, 217 Viral, 10, 28, 30, 35, 45, 53, 174, 197, 215, 217 Viral Load, 10, 53, 217 Viral Proteins, 28, 217 Virulence, 159, 215, 217 Virus, 10, 24, 30, 35, 37, 53, 153, 179, 180, 208, 215, 217, 218 Visceral, 159, 170, 188, 218 Visceral Afferents, 159, 218 Visual field, 197, 208, 218 Vitamin A, 185, 208, 218 Vitreous, 166, 207, 218 Vitreous Body, 166, 207, 218 Vitro, 20, 35, 45, 55, 218 Vivo, 16, 20, 23, 45, 46, 55, 61, 62, 189, 218 Volition, 186, 218 W White blood cell, 157, 189, 201, 218 Wound Healing, 190, 218 X Xenograft, 156, 218 X-ray, 56, 90, 103, 168, 169, 190, 196, 205, 206, 211, 218
232
Basal Ganglia
Y Yeasts, 200, 218
Z Zymogen, 204, 218
