PARKINSON DISEASE A
3-in-1
Medical
Reference
A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers TO INTERNET REFERENCES
PARKINSON DISEASE A BIBLIOGRAPHY AND DICTIONARY FOR PHYSICIANS, PATIENTS, AND GENOME RESEARCHERS
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. 7404 Trade Street San Diego, CA 92121 USA Copyright ©2007 by ICON Group International, Inc. Copyright ©2007 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., 1960Parkinson Disease: A Bibliography and Dictionary for Physicians, Patients, and Genome Researchers/ James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-11270-1 1. Parkinson Disease-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 Parkinson disease. 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 Chaired Professor of Management Science 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. 7404 Trade Street San Diego, CA 92121 USA Fax: 858-635-9414 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON PARKINSON DISEASE ................................................................................ 3 Overview........................................................................................................................................ 3 Genetics Home Reference ............................................................................................................... 3 What Is Parkinson Disease? .......................................................................................................... 3 How Common Is Parkinson Disease? ............................................................................................ 4 What Genes Are Related to Parkinson Disease?............................................................................ 4 How Do People Inherit Parkinson Disease? .................................................................................. 5 Where Can I Find Additional Information about Parkinson Disease? .......................................... 5 References....................................................................................................................................... 8 What Is the Official Name of the LRRK2 Gene?............................................................................ 9 What Is the Normal Function of the LRRK2 Gene? ...................................................................... 9 What Conditions Are Related to the LRRK2 Gene? .................................................................... 10 Where Is the LRRK2 Gene Located? ............................................................................................ 10 References..................................................................................................................................... 11 What Is the Official Name of the PARK2 Gene? ......................................................................... 12 What Is the Normal Function of the PARK2 Gene?.................................................................... 12 What Conditions Are Related to the PARK2 Gene?.................................................................... 13 Where Is the PARK2 Gene Located?............................................................................................ 13 References..................................................................................................................................... 14 What Is the Official Name of the PARK7 Gene? ......................................................................... 15 What Is the Normal Function of the PARK7 Gene?.................................................................... 15 What Conditions Are Related to the PARK7 Gene?.................................................................... 15 Where Is the PARK7 Gene Located?............................................................................................ 15 References..................................................................................................................................... 16 What Is the Official Name of the PINK1 Gene? .......................................................................... 17 What Is the Normal Function of the PINK1 Gene?..................................................................... 17 What Conditions Are Related to the PINK1 Gene?..................................................................... 18 Where Is the PINK1 Gene Located?............................................................................................. 18 References..................................................................................................................................... 18 What Is the Official Name of the SNCA Gene? ........................................................................... 19 What Is the Normal Function of the SNCA Gene? ..................................................................... 20 What Conditions Are Related to the SNCA Gene? ..................................................................... 20 Where Is the SNCA Gene Located? ............................................................................................. 21 References..................................................................................................................................... 21 What Is the Official Name of the GBA Gene?.............................................................................. 23 What Is the Normal Function of the GBA Gene? ........................................................................ 23 What Conditions Are Related to the GBA Gene? ........................................................................ 23 Where Is the GBA Gene Located? ................................................................................................ 24 References..................................................................................................................................... 25 What Is the Official Name of the SNCAIP Gene? ....................................................................... 26 What Is the Normal Function of the SNCAIP Gene?.................................................................. 26 What Conditions Are Related to the SNCAIP Gene?.................................................................. 26 Where Is the SNCAIP Gene Located?.......................................................................................... 26 References..................................................................................................................................... 27 What Is the Official Name of the UCHL1 Gene?......................................................................... 28 What Is the Normal Function of the UCHL1 Gene? ................................................................... 28 What Conditions Are Related to the UCHL1 Gene? ................................................................... 28 Where Is the UCHL1 Gene Located? ........................................................................................... 28 References..................................................................................................................................... 29 Federally Funded Research on Parkinson Disease ....................................................................... 30
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The National Library of Medicine: PubMed ................................................................................ 50 CHAPTER 2. ALTERNATIVE MEDICINE AND PARKINSON DISEASE ................................................ 94 Overview...................................................................................................................................... 94 National Center for Complementary and Alternative Medicine.................................................. 94 Additional Web Resources ......................................................................................................... 100 General References ..................................................................................................................... 100 CHAPTER 3. BOOKS ON PARKINSON DISEASE .............................................................................. 102 Overview.................................................................................................................................... 102 Book Summaries: Online Booksellers......................................................................................... 102 APPENDIX A. HELP ME UNDERSTAND GENETICS ....................................................................... 106 Overview.................................................................................................................................... 106 The Basics: Genes and How They Work..................................................................................... 106 Genetic Mutations and Health................................................................................................... 117 Inheriting Genetic Conditions ................................................................................................... 123 Genetic Consultation ................................................................................................................. 131 Genetic Testing .......................................................................................................................... 133 Gene Therapy ............................................................................................................................. 139 The Human Genome Project and Genomic Research................................................................. 142 APPENDIX B. PHYSICIAN RESOURCES ........................................................................................... 145 Overview.................................................................................................................................... 145 NIH Guidelines.......................................................................................................................... 145 NIH Databases........................................................................................................................... 146 Other Commercial Databases..................................................................................................... 149 The Genome Project and Parkinson Disease.............................................................................. 149 APPENDIX C. PATIENT RESOURCES .............................................................................................. 154 Overview.................................................................................................................................... 154 Patient Guideline Sources.......................................................................................................... 154 Finding Associations.................................................................................................................. 157 Resources for Patients and Families........................................................................................... 158 ONLINE GLOSSARIES................................................................................................................ 159 Online Dictionary Directories ................................................................................................... 159 PARKINSON DISEASE DICTIONARY ................................................................................... 160 INDEX .............................................................................................................................................. 205
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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 Parkinson disease 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 Parkinson disease, 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 Parkinson disease, from the essentials to the most advanced areas of research. Special attention has been paid to present the genetic basis and pattern of inheritance of Parkinson disease. 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 Parkinson disease. 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 Parkinson disease, 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. We hope these resources will prove useful to the widest possible audience seeking information on Parkinson disease. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/.
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CHAPTER 1. STUDIES ON PARKINSON DISEASE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Parkinson disease. For those interested in basic information about Parkinson disease, we begin with a condition summary published by the National Library of Medicine.
Genetics Home Reference Genetics Home Reference (GHR) is the National Library of Medicine’s Web site for consumer information about genetic conditions and the genes or chromosomes responsible for those conditions. Here you can find a condition summary on Parkinson disease that describes the major features of the condition, provides information about the condition’s genetic basis, and explains its pattern of inheritance. In addition, a summary of the gene or chromosome related to Parkinson disease is provided.2 The Genetics Home Reference has recently published the following summary for Parkinson disease:
What Is Parkinson Disease?3 Parkinson disease is a progressive disorder of the central nervous system. The disorder affects several regions of the brain, including an area called the substantia nigra that controls balance and movement. Parkinson disease may also affect regions of the brain that regulate involuntary functions such as blood pressure and heart activity. Often the first symptom of Parkinson disease is trembling or shaking (tremor) of a limb, especially when the body is at rest. Typically, the tremor begins on one side of the body, usually in one hand. Tremors can also affect the arms, legs, feet, and face. Other 2 3
This section has been adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/.
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/condition=parkinsondisease.
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characteristic symptoms include rigidity or stiffness of the limbs and trunk, slow movement (bradykinesia) or the inability to move (akinesia), and impaired balance and coordination (postural instability). Many Parkinson disease symptoms occur when nerve cells (neurons) in the substantia nigra die or become impaired. Normally, these cells produce a chemical messenger called dopamine, which transmits signals within the brain to produce smooth physical movements. When these dopamine-producing neurons die or become impaired, communication between the brain and muscles weakens, and eventually, the brain is unable to control muscle movement. In most cases of Parkinson disease, protein deposits called Lewy bodies appear in dead or dying dopamine-producing neurons. (Cases without Lewy bodies are sometimes referred to as familial parkinsonism instead of Parkinson disease.) It is unclear whether Lewy bodies play a role in killing nerve cells, or if they are part of a protective process. Generally, Parkinson disease that begins after age 50 years is called late onset, and it is called early onset if signs and symptoms begin before age 50. Cases that begin before age 20 years are sometimes referred to as juvenile onset.
How Common Is Parkinson Disease? Parkinson disease affects more than 1 million people in North America and more than 4 million people worldwide. In the United States, Parkinson disease occurs in approximately 13 per 100,000 people and about 50,000 new cases are identified each year. The number of cases is rising with the increasing age of the general population.
What Genes Are Related to Parkinson Disease? Mutations in the LRRK2 (http://ghr.nlm.nih.gov/gene=lrrk2), PARK2 (http://ghr.nlm.nih.gov/gene=park2), PARK7 (http://ghr.nlm.nih.gov/gene=park7), PINK1 (http://ghr.nlm.nih.gov/gene=pink1), and SNCA (http://ghr.nlm.nih.gov/gene=snca) genes cause Parkinson disease. The GBA (http://ghr.nlm.nih.gov/gene=gba), SNCAIP (http://ghr.nlm.nih.gov/gene=sncaip), and UCHL1 (http://ghr.nlm.nih.gov/gene=uchl1) genes are associated with Parkinson disease. Most cases of Parkinson disease are classified as sporadic and occur in people with no apparent history of the disorder in their family. Although the cause of these cases remains unclear, sporadic cases probably result from a complex interaction of environmental and genetic factors. Additionally, certain drugs may cause Parkinson-like symptoms. Approximately 15 percent of people with Parkinson disease have a family history of this disorder. These familial cases are caused by mutations in the LRRK2, PARK2, PARK7, PINK1, or SNCA gene, or by alterations in genes that have not been identified. Mutations in some of these genes may also play a role in cases that appear to be sporadic. It is not fully understood how mutations in the LRRK2, PARK2, PARK7, PINK1, or SNCA gene cause Parkinson disease. Some mutations appear to disturb the cell machinery that
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breaks down (degrades) unwanted proteins. As a result, undegraded proteins accumulate, leading to the impairment or death of dopamine-producing neurons. Other mutations may involve mitochondria, the energy-producing structures within cells. As a byproduct of energy production, mitochondria make unstable molecules, called free radicals, that can damage the cell. Normally, the cell neutralizes free radicals, but some gene mutations may disrupt this neutralization process. As a result, free radicals may accumulate and impair or kill dopamine-producing neurons. In some families, alterations in the GBA, SNCAIP, or UCHL1 gene appear to modify the risk of developing Parkinson disease. Researchers have identified some genetic changes that may reduce the risk of developing the disease, while other gene alterations seem to increase the risk.
How Do People Inherit Parkinson Disease? Most cases of Parkinson disease occur in people with no family history of the disorder. The inheritance pattern, if any, is unknown. Among familial cases of Parkinson disease, the inheritance pattern differs depending on the gene that is altered. If the LRRK2 or SNCA gene is involved, the disorder is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. Parkinson disease is inherited in an autosomal recessive pattern if the PARK2, PARK7, or PINK1 gene is involved. This type of inheritance means that each cell has two copies of the altered gene. Most often, the parents of an individual with autosomal recessive Parkinson disease are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder. (Sometimes, autosomal recessive cases that do not have Lewy bodies are referred to as parkinsonism to distinguish them from Parkinson disease with Lewy bodies.) The increased risk of Parkinson disease or parkinsonism associated with mutations in the GBA gene is inherited in an autosomal recessive pattern. SNCAIP and UCHL1 mutations have been identified in just a few individuals. It is unclear whether these mutations are related to Parkinson disease, and the inheritance pattern is unknown.
Where Can I Find Additional Information about Parkinson Disease? You may find the following resources about Parkinson disease helpful. These materials are written for the general public. NIH Publications - National Institutes of Health •
National Center for Biotechnology Information: Genes and Disease: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=gnd.section.212
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National Human Genome Research Institute: Learning About Parkinson's Disease: http://www.genome.gov/page.cfm?pageID=10001217
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•
National Institute of Environmental Health Sciences: Role of the Environment in Parkinson's Disease: http://www.niehs.nih.gov/oc/factsheets/parkinson/home.htm
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National Institute of Mental Health: Depression and Parkinson's Disease: http://www.nimh.nih.gov/publicat/depparkinson.cfm
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National Institute of Neurological Disorders and Stroke: Backgrounder: http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease_backgro under.htm
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National Institute of Neurological Disorders and Stroke: Challenges, Progress, and Promise: http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_research.htm
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National Institute of Neurological Disorders and Stroke: Deep Brain Stimulation for Parkinson's Disease: http://www.ninds.nih.gov/disorders/deep_brain_stimulation/deep_brain_stimulation. htm
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National Institute of Neurological Disorders and Stroke: Hope Through Research: http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease.ht
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National Institute of Neurological Disorders and Stroke: Information Page: http://www.ninds.nih.gov/disorders/parkinsons_disease/parkinsons_disease.htmm
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National Institute of Neurological Disorders and Stroke: Life and Death of a Neuron: http://www.ninds.nih.gov/disorders/brain_basics/ninds_neuron.htm
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National Institutes of Neurological Disorders and Stroke: Diagnosis of Depression in Parkinson's Disease: http://www.ninds.nih.gov/news_and_events/proceedings/depression_summary.htm
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National Institutes of Neurological Disorders and Stroke: Parkinson's Disease Research Web: http://www.ninds.nih.gov/funding/research/parkinsonsweb/index.htm MedlinePlus - Health Information
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Encyclopedia: Parkinson's disease: http://www.nlm.nih.gov/medlineplus/ency/article/000755.htm
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Encyclopedia: Parkinson's disease - resources: http://www.nlm.nih.gov/medlineplus/ency/article/002196.htm
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Health Topic: Lewy Body Disease: http://www.nlm.nih.gov/medlineplus/lewybodydisease.html
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Health Topic: Parkinson's Disease: http://www.nlm.nih.gov/medlineplus/parkinsonsdisease.html Educational Resources - Information Pages
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Duke Center for Human Genetics: http://www.chg.duke.edu/diseases/pd.html
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Madisons Foundation: Juvenile Parkinson's Disease: http://www.madisonsfoundation.org/content/3/1/display.asp?did=453
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Madisons Foundation: Young Onset Parkinson's Disease: http://www.madisonsfoundation.org/content/3/1/display.asp?did=479
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Mayo Clinic: http://www.mayoclinic.org/parkinsons-disease/index.html
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National Highway Traffic Safety Administration: http://www.nhtsa.dot.gov/people/injury/olddrive/Parkinsons%20Web/index.html
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Nemours Foundation: Kids Health: http://kidshealth.org/kid/grownup/conditions/parkinson.html
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New York Online Access to Health (NOAH): http://www.noah-health.org/en/bns/disorders/parkinson/index.html
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Orphanet: http://www.orpha.net//consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2828 Patient Support - for Patients and Families
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American Parkinson Disease Association: http://www.apdaparkinson.org/
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Bachmann-Strauss Dystonia and Parkinson Foundation: http://www.dystoniaparkinsons.org/index.cfm?fuseaction=home.viewPage&page_id=22A9BBC79228-A9D1-5F731EA5606F7856
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Michael J. Fox Foundation for Parkinson's Research: http://www.michaeljfox.org/parkinsons/index.php
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National Organization for Rare Disorders (NORD): http://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Parkinson\
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National Parkinson Foundation: http://www.parkinson.org/site/pp.asp?c=9dJFJLPwB&b=71354
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Parkinson's Action Network: http://www.parkinsonsaction.org/
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Parkinson's Disease Foundation: http://www.pdf.org/AboutPD/
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Parkinson's Resource Organization: http://www.parkinsonsresource.org
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The Parkinson's Institute: http://www.parkinsonsinstitute.org/
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The Parkinson Alliance: http://www.parkinsonalliance.net/
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We Move: http://www.wemove.org/par/default.htm
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Professional Resources You may also be interested in these resources, which are designed for healthcare professionals and researchers. •
Gene Reviews - Clinical summary: http://ghr.nlm.nih.gov/condition=parkinsondisease/show/Gene+Reviews;jsessionid= BD942BD30D0E9A2D2CF316053BE92AD4
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Gene Tests - DNA tests ordered by healthcare professionals: http://ghr.nlm.nih.gov/condition=parkinsondisease/show/Gene+Tests;jsessionid=BD 942BD30D0E9A2D2CF316053BE92AD4
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ClinicalTrials.gov - Linking patients to medical research: http://clinicaltrials.gov/search/condition=%22parkinson+disease%22?recruiting=false
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PubMed - Recent literature: http://ghr.nlm.nih.gov/condition=parkinsondisease/show/PubMed;jsessionid=BD942 BD30D0E9A2D2CF316053BE92AD4
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OMIM - Genetic disorder catalog: http://ghr.nlm.nih.gov/condition=parkinsondisease/show/OMIM;jsessionid=BD942B D30D0E9A2D2CF316053BE92AD4
References These sources were used to develop the Genetics Home Reference condition summary on Parkinson disease. •
Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. PubMed citation
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Emery, Alan E H; Rimoin, David L; Emery & Rimoin's principles and practice of medical genetics.; 4th ed. / edited by David L. Rimoin. [et al.]; London; New York : Churchill Livingstone, 2002. p3077-3081. NLM Catalog
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Farrer MJ. Genetics of Parkinson disease: paradigm shifts and future prospects. Nat Rev Genet. 2006 Apr;7(4):306-18. PubMed citation
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Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. PubMed citation
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Gene Review: Parkinson Disease
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Hardy J, Cai H, Cookson MR, Gwinn-Hardy K, Singleton A. Genetics of Parkinson's disease and parkinsonism. Ann Neurol. 2006 Oct;60(4):389-98. PubMed citation
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Huang Y, Cheung L, Rowe D, Halliday G. Genetic contributions to Parkinson's disease. Brain Res Brain Res Rev. 2004 Aug;46(1):44-70. Review. PubMed citation
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Jain S, Wood NW, Healy DG. Molecular genetic pathways in Parkinson's disease: a review. Clin Sci (Lond). 2005 Oct;109(4):355-64. Review. PubMed citation
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Lang AE, Lozano AM. Parkinson's disease. First of two parts. N Engl J Med. 1998 Oct 8;339(15):1044-53. Review. No abstract available. PubMed citation
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Lewthwaite AJ, Nicholl DJ. Genetics of parkinsonism. Curr Neurol Neurosci Rep. 2005 Sep;5(5):397-404. Review. PubMed citation
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Lim KL, Dawson VL, Dawson TM. The cast of molecular characters in Parkinson's disease: felons, conspirators, and suspects. Ann N Y Acad Sci. 2003 Jun;991:80-92. Review. PubMed citation
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Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. PubMed citation
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National Institute of Neurological Disorders and Stroke: Backgrounder
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Pankratz N, Foroud T. Genetics of Parkinson Disease. Neurorx. 2004 Apr;1(2):235-242. PubMed citation
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Samii A, Nutt JG, Ransom BR. Parkinson's disease. Lancet. 2004 May 29;363(9423):178393. Review. PubMed citation
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Singleton AB. Altered alpha-synuclein homeostasis causing Parkinson's disease: the potential roles of dardarin. Trends Neurosci. 2005 Aug;28(8):416-21. Review. PubMed citation
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Van Den Eeden SK, Tanner CM, Bernstein AL, Fross RD, Leimpeter A, Bloch DA, Nelson LM. Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity. Am J Epidemiol. 2003 Jun 1;157(11):1015-22. PubMed citation
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Vila M, Przedborski S. Genetic clues to the pathogenesis of Parkinson's disease. Nat Med. 2004 Jul;10 Suppl:S58-62. Review. PubMed citation
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von Bohlen und Halbach O, Schober A, Krieglstein K. Genes, proteins, and neurotoxins involved in Parkinson's disease. Prog Neurobiol. 2004 Jun;73(3):151-77. Review. PubMed citation
A summary of the genes related to Parkinson disease is provided below:
What Is the Official Name of the LRRK2 Gene?4 The official name of this gene is “leucine-rich repeat kinase 2.” LRRK2 is the gene's official symbol. The LRRK2 gene is also known by other names, listed below.
What Is the Normal Function of the LRRK2 Gene? The LRRK2 gene provides instructions for making a protein called dardarin. The LRRK2 gene is active in the brain and other tissues throughout the body, but little is known about this gene or the dardarin protein.
4
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=lrrk2;jsessionid=BD942BD30D0E9A2D2CF316053BE92AD4.
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Studies of the gene's instructions have revealed some clues about dardarin's function. Part of the LRRK2 gene provides instructions for making a protein segment that is rich in a protein building block (an amino acid) called leucine. Proteins with leucine-rich regions appear to play a role in activities that require protein-protein interactions, such as transmitting signals or helping to assemble the cell's structural framework (cytoskeleton). Other parts of the LRRK2 gene provide instructions for protein regions called the ROC-COR domain and the WD40 domain. These domains also suggest that dardarin is capable of multiple proteinprotein interactions. Additional research findings indicate that dardarin has an enzyme activity known as kinase. Proteins with kinase activity assist in the transfer of a phosphate group (a cluster of oxygen and phosphate atoms) from the energy molecule ATP to amino acids in certain proteins. This phosphate transfer is called phosphorylation, and it is an essential step in turning on and off many cell activities. Dardarin may have a second enzyme activity referred to as a GTPase activity. This activity is associated with a region of the protein called the ROC domain. The ROC domain may act as a molecular switch that controls the overall shape of the dardarin protein.
What Conditions Are Related to the LRRK2 Gene? Parkinson Disease - Caused by Mutations in the LRRK2 Gene Researchers have identified at least 20 LRRK2 mutations in families with late-onset Parkinson disease. These mutations replace one amino acid with another amino acid in the dardarin protein, which affects the protein's structure and function. Two mutations appear to increase dardarin's kinase activity, but little is known about the effect of other LRRK2 mutations or how they lead to Parkinson disease.
Where Is the LRRK2 Gene Located? Cytogenetic Location: 12q12 Molecular Location on chromosome 12: base pairs 38,905,085 to 39,051,869
The LRRK2 gene is located on the long (q) arm of chromosome 12 at position 12.
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More precisely, the LRRK2 gene is located from base pair 38,905,085 to base pair 39,051,869 on chromosome 12.
References These sources were used to develop the Genetics Home Reference gene summary on the LRRK2 gene. •
Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. PubMed citation
•
Di Fonzo A, Rohe CF, Ferreira J, Chien HF, Vacca L, Stocchi F, Guedes L, Fabrizio E, Manfredi M, Vanacore N, Goldwurm S, Breedveld G, Sampaio C, Meco G, Barbosa E, Oostra BA, Bonifati V. A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease. Lancet. 2005 Jan 29;365(9457):412-415. PubMed citation
•
Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. PubMed citation
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Gilks WP, Abou-Sleiman PM, Gandhi S, Jain S, Singleton A, Lees AJ, Shaw K, Bhatia KP, Bonifati V, Quinn NP, Lynch J, Healy DG, Holton JL, Revesz T, Wood NW. A common LRRK2 mutation in idiopathic Parkinson's disease. Lancet. 2005 Jan 29;365(9457):415416. PubMed citation
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Guo L, Wang W, Chen SG. Leucine-rich repeat kinase 2: Relevance to Parkinson's disease. Int J Biochem Cell Biol. 2006 Sep;38(9):1469-75. Epub 2006 Mar 2. PubMed citation
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Lesage S, Durr A, Tazir M, Lohmann E, Leutenegger AL, Janin S, Pollak P, Brice A; French Parkinson's Disease Genetics Study Group. LRRK2 G2019S as a cause of Parkinson's disease in North African Arabs. N Engl J Med. 2006 Jan 26;354(4):422-3. No abstract available. PubMed citation
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Mata IF, Wedemeyer WJ, Farrer MJ, Taylor JP, Gallo KA. LRRK2 in Parkinson's disease: protein domains and functional insights. Trends Neurosci. 2006 Apr 6; [Epub ahead of print]. PubMed citation
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Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. PubMed citation
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Nichols WC, Pankratz N, Hernandez D, Paisan-Ruiz C, Jain S, Halter CA, Michaels VE, Reed T, Rudolph A, Shults CW, Singleton A, Foroud T. Genetic screening for a single common LRRK2 mutation in familial Parkinson's disease. Lancet. 2005 Jan 29;365(9457):410-412. PubMed citation
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OMIM
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Ozelius LJ, Senthil G, Saunders-Pullman R, Ohmann E, Deligtisch A, Tagliati M, Hunt AL, Klein C, Henick B, Hailpern SM, Lipton RB, Soto-Valencia J, Risch N, Bressman SB. LRRK2 G2019S as a cause of Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2006 Jan 26;354(4):424-5. No abstract available. PubMed citation
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Paisan-Ruiz C, Jain S, Evans EW, Gilks WP, Simon J, van der Brug M, de Munain AL, Aparicio S, Gil AM, Khan N, Johnson J, Martinez JR, Nicholl D, Carrera IM, Pena AS, de Silva R, Lees A, Marti-Masso JF, Perez-Tur J, Wood NW, Singleton AB. Cloning of the
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gene containing mutations that cause PARK8-linked Parkinson's disease. Neuron. 2004 Nov 18;44(4):595-600. PubMed citation •
Smith WW, Pei Z, Jiang H, Moore DJ, Liang Y, West AB, Dawson VL, Dawson TM, Ross CA. Leucine-rich repeat kinase 2 (LRRK2) interacts with parkin, and mutant LRRK2 induces neuronal degeneration. Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18676-81. Epub 2005 Dec 13. PubMed citation
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West AB, Moore DJ, Biskup S, Bugayenko A, Smith WW, Ross CA, Dawson VL, Dawson TM. Parkinson's disease-associated mutations in leucine-rich repeat kinase 2 augment kinase activity. Proc Natl Acad Sci U S A. 2005 Nov 15;102(46):16842-7. Epub 2005 Nov 3. PubMed citation
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Zimprich A, Biskup S, Leitner P, Lichtner P, Farrer M, Lincoln S, Kachergus J, Hulihan M, Uitti RJ, Calne DB, Stoessl AJ, Pfeiffer RF, Patenge N, Carbajal IC, Vieregge P, Asmus F, Muller-Myhsok B, Dickson DW, Meitinger T, Strom TM, Wszolek ZK, Gasser T. Mutations in LRRK2 cause autosomal-dominant parkinsonism with pleomorphic pathology. Neuron. 2004 Nov 18;44(4):601-7. PubMed citation
What Is the Official Name of the PARK2 Gene?5 The official name of this gene is “Parkinson disease (autosomal recessive, juvenile) 2, parkin.” PARK2 is the gene's official symbol. The PARK2 gene is also known by other names, listed below.
What Is the Normal Function of the PARK2 Gene? The PARK2 gene, one of the largest human genes, provides instructions for making a protein called parkin. Parkin plays a role in the cell machinery that breaks down (degrades) unwanted proteins by tagging damaged and excess proteins with molecules called ubiquitin. Ubiquitin serves as a signal to move unwanted proteins into specialized cell structures known as proteasomes, where the proteins are degraded. The ubiquitinproteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth. Because of its activity in the ubiquitin-proteasome system, parkin belongs to a protein group called ubiquitin E3 ligases. Studies of the structure and activity of parkin have led researchers to suggest other activities for this protein. Parkin may act as a tumor suppressor protein, which means it prevents cells from growing and dividing too rapidly or in an uncontrolled way. Parkin may also regulate the supply and release of sacs, called synaptic vesicles, from nerve cells. Synaptic vesicles contain chemical messengers that transmit signals from one nerve cell to another.
5
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=park2.
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What Conditions Are Related to the PARK2 Gene? Parkinson Disease - Caused by Mutations in the PARK2 Gene Researchers have identified more than 100 PARK2 mutations that cause juvenile Parkinson disease and some adult-onset cases. Some mutations lead to an abnormally small parkin protein, which is nonfunctional and degrades rapidly. Other mutations change the building blocks (amino acids) used to make parkin, and the altered protein cannot function properly. PARK2 mutations usually lead to a loss of parkin activity. Cancers - Associated with the PARK2 Gene Researchers have identified more than 100 PARK2 mutations that cause juvenile Parkinson disease and some adult-onset cases. Some mutations lead to an abnormally small parkin protein, which is nonfunctional and degrades rapidly. Other mutations change the building blocks (amino acids) used to make parkin, and the altered protein cannot function properly. PARK2 mutations usually lead to a loss of parkin activity. Other Disorders - Increased Risk from Variations of the PARK2 Gene The PARK2 gene spans part of a fragile area (known as FRA6E) on chromosome 6. This fragile area is unstable and prone to breakage and rearrangement. In tumors from some patients with ovarian or lung cancer, segments of the PARK2 gene within the FRA6E region are deleted or duplicated. As a result of these alterations, parkin activity is absent or reduced. These findings suggest that the PARK2 gene normally acts as a tumor suppressor gene, by restraining cell division and growth. If it is altered, cells can grow and divide in an uncontrolled manner, leading to a tumor.
Where Is the PARK2 Gene Located? Cytogenetic Location: 6q25.2-q27 Molecular Location on chromosome 6: base pairs 161,689,660 to 163,068,792
The PARK2 gene is located on the long (q) arm of chromosome 6 between positions 25.2 and 27.
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More precisely, the PARK2 gene is located from base pair 161,689,660 to base pair 163,068,792 on chromosome 6.
References These sources were used to develop the Genetics Home Reference gene summary on the PARK2 gene. •
Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. PubMed citation
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Cookson MR. The biochemistry of Parkinson's disease. Annu Rev Biochem. 2005;74:2952. Review. PubMed citation
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Denison SR, Callahan G, Becker NA, Phillips LA, Smith DI. Characterization of FRA6E and its potential role in autosomal recessive juvenile parkinsonism and ovarian cancer. Genes Chromosomes Cancer. 2003 Sep;38(1):40-52. PubMed citation
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Denison SR, Wang F, Becker NA, Schule B, Kock N, Phillips LA, Klein C, Smith DI. Alterations in the common fragile site gene Parkin in ovarian and other cancers. Oncogene. 2003 Nov 13;22(51):8370-8. PubMed citation
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Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. PubMed citation
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Lim KL, Dawson VL, Dawson TM. The cast of molecular characters in Parkinson's disease: felons, conspirators, and suspects. Ann N Y Acad Sci. 2003 Jun;991:80-92. Review. PubMed citation
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Mira MT, Alcais A, Nguyen VT, Moraes MO, Di Flumeri C, Vu HT, Mai CP, Nguyen TH, Nguyen NB, Pham XK, Sarno EN, Alter A, Montpetit A, Moraes ME, Moraes JR, Dore C, Gallant CJ, Lepage P, Verner A, Van De Vosse E, Hudson TJ, Abel L, Schurr E. Susceptibility to leprosy is associated with PARK2 and PACRG. Nature. 2004 Feb 12;427(6975):636-40. Epub 2004 Jan 25. PubMed citation
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Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. PubMed citation
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OMIM: parkin and fragile site FRA6E
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Pankratz N, Foroud T. Genetics of Parkinson Disease. Neurorx. 2004 Apr;1(2):235-242. PubMed citation
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Picchio MC, Martin ES, Cesari R, Calin GA, Yendamuri S, Kuroki T, Pentimalli F, Sarti M, Yoder K, Kaiser LR, Fishel R, Croce CM. Alterations of the tumor suppressor gene Parkin in non-small cell lung cancer. Clin Cancer Res. 2004 Apr 15;10(8):2720-4. PubMed citation
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Pramstaller PP, Schlossmacher MG, Jacques TS, Scaravilli F, Eskelson C, Pepivani I, Hedrich K, Adel S, Gonzales-McNeal M, Hilker R, Kramer PL, Klein C. Lewy body Parkinson's disease in a large pedigree with 77 Parkin mutation carriers. Ann Neurol. 2005 Sep;58(3):411-22. PubMed citation
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Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet. 2000 Jul;25(3):302-5. PubMed citation
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von Coelln R, Dawson VL, Dawson TM. Parkin-associated Parkinson's disease. Cell Tissue Res. 2004 Oct;318(1):175-84. Epub 2004 Jul 30. PubMed citation
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West AB, Maidment NT. Genetics of parkin-linked disease. Hum Genet. 2004 Mar;114(4):327-36. Epub 2004 Jan 15. Review. PubMed citation
What Is the Official Name of the PARK7 Gene?6 The official name of this gene is “Parkinson disease (autosomal recessive, early onset) 7.” PARK7 is the gene's official symbol. The PARK7 gene is also known by other names, listed below.
What Is the Normal Function of the PARK7 Gene? The PARK7 gene provides instructions for making the DJ-1 protein. Studies indicate that the DJ-1 protein has several functions, although none are fully understood. The DJ-1 protein may help protect cells, particularly brain cells, from oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that damage or kill cells. Additionally, the DJ-1 protein may serve as a chaperone molecule that helps fold newly produced proteins into the proper 3-dimensional shape and helps refold damaged proteins. Chaperone molecules also assist in delivering selected proteins to proteasomes, the cell machinery that breaks down unwanted molecules. Researchers also suggest that the DJ-1 protein may play a role in activities that produce and process RNA, a chemical cousin of DNA.
What Conditions Are Related to the PARK7 Gene? Parkinson Disease - Caused by Mutations in the PARK7 Gene Researchers have identified more than 10 PARK7 mutations that cause early-onset Parkinson disease. In some cases, a large portion of the PARK7 gene is deleted, and no functional DJ-1 protein is made. Other mutations lead to an abnormally small DJ-1 protein or change the building blocks (amino acids) used to make the protein. The altered DJ-1 protein is unstable and does not function properly, if at all.
Where Is the PARK7 Gene Located? Cytogenetic Location: 1p36.33-p36.12
6
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=park7;jsessionid=BD942BD30D0E9A2D2CF316053BE92AD4.
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Parkinson Disease
Molecular Location on chromosome 1: base pairs 7,944,379 to 7,967,925
The PARK7 gene is located on the short (p) arm of chromosome 1 between positions 36.33 and 36.12. More precisely, the PARK7 gene is located from base pair 7,944,379 to base pair 7,967,925 on chromosome 1.
References These sources were used to develop the Genetics Home Reference gene summary on the PARK7 gene. •
Abou-Sleiman PM, Healy DG, Quinn N, Lees AJ, Wood NW. The role of pathogenic DJ1 mutations in Parkinson's disease. Ann Neurol. 2003 Sep;54(3):283-6. PubMed citation
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Abou-Sleiman PM, Healy DG, Wood NW. Causes of Parkinson's disease: genetics of DJ1. Cell Tissue Res. 2004 Oct;318(1):185-8. Epub 2004 Jun 26. PubMed citation
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Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. PubMed citation
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Bonifati V, Oostra BA, Heutink P. Linking DJ-1 to neurodegeneration offers novel insights for understanding the pathogenesis of Parkinson's disease. J Mol Med. 2004 Mar;82(3):163-74. Epub 2004 Jan 08. Review. PubMed citation
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Bonifati V, Rizzu P, van Baren MJ, Schaap O, Breedveld GJ, Krieger E, Dekker MC, Squitieri F, Ibanez P, Joosse M, van Dongen JW, Vanacore N, van Swieten JC, Brice A, Meco G, van Duijn CM, Oostra BA, Heutink P. Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2003 Jan 10;299(5604):256-9. Epub 2002 Nov 21. PubMed citation
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Cookson MR. Pathways to Parkinsonism. Neuron. 2003 Jan 9;37(1):7-10. Review. PubMed citation
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Cookson MR. The biochemistry of Parkinson's disease. Annu Rev Biochem. 2005;74:2952. Review. PubMed citation
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Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. PubMed citation
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Miller DW, Ahmad R, Hague S, Baptista MJ, Canet-Aviles R, McLendon C, Carter DM, Zhu PP, Stadler J, Chandran J, Klinefelter GR, Blackstone C, Cookson MR. L166P mutant
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DJ-1, causative for recessive Parkinson's disease, is degraded through the ubiquitinproteasome system. J Biol Chem. 2003 Sep 19;278(38):36588-95. Epub 2003 Jul 08. PubMed citation •
Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. PubMed citation
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Pankratz N, Foroud T. Genetics of Parkinson Disease. Neurorx. 2004 Apr;1(2):235-242. PubMed citation
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Taira T, Saito Y, Niki T, Iguchi-Ariga SM, Takahashi K, Ariga H. DJ-1 has a role in antioxidative stress to prevent cell death. EMBO Rep. 2004 Feb;5(2):213-8. Epub 2004 Jan 23. Erratum in: EMBO Rep. 2004 Apr;5(4):430. PubMed citation
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Zhou W, Zhu M, Wilson MA, Petsko GA, Fink AL. The oxidation state of DJ-1 regulates its chaperone activity toward alpha-synuclein. J Mol Biol. 2006 Mar 3;356(4):1036-48. Epub 2005 Dec 27. PubMed citation
What Is the Official Name of the PINK1 Gene?7 The official name of this gene is “PTEN induced putative kinase 1.” PINK1 is the gene's official symbol. The PINK1 gene is also known by other names, listed below.
What Is the Normal Function of the PINK1 Gene? The PINK1 gene produces a protein called PTEN induced putative kinase 1. This protein is found in cells throughout the body, with highest levels in the heart, muscles, and testes. Within cells, PTEN induced putative kinase 1 is located in the mitochondria, the energyproducing centers that provide power for cellular activities. The function of PTEN induced putative kinase 1 is not fully understood. It appears to help protect mitochondria from malfunctioning during periods of cellular stress, such as unusually high energy demands. Researchers believe that two specialized regions of PTEN induced putative kinase 1 are essential for the protein to function properly. One region, called the mitochondrial-targeting motif, serves as a delivery address. PTEN induced putative kinase 1 is produced outside the mitochondria, and this motif helps ensure that the protein is delivered to the mitochondria. Another region, called the kinase domain, probably carries out the protein's protective function.
7
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=pink1.
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Parkinson Disease
What Conditions Are Related to the PINK1 Gene? Parkinson Disease - Caused by Mutations in the PINK1 Gene Researchers have identified more than 20 PINK1 mutations that cause early-onset Parkinson disease. Some mutations change one of the protein building blocks (amino acids) used to make PTEN induced putative kinase 1. Other mutations lead to an abnormally small protein.
Where Is the PINK1 Gene Located? Cytogenetic Location: 1p36 Molecular Location on chromosome 1: base pairs 20,832,534 to 20,850,590
The PINK1 gene is located on the short (p) arm of chromosome 1 at position 36. More precisely, the PINK1 gene is located from base pair 20,832,534 to base pair 20,850,590 on chromosome 1.
References These sources were used to develop the Genetics Home Reference gene summary on the PINK1 gene. •
Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. PubMed citation
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Beilina A, Van Der Brug M, Ahmad R, Kesavapany S, Miller DW, Petsko GA, Cookson MR. Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability. Proc Natl Acad Sci U S A. 2005 Apr 19;102(16):5703-8. Epub 2005 Apr 11. PubMed citation
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Clark IE, Dodson MW, Jiang C, Cao JH, Huh JR, Seol JH, Yoo SJ, Hay BA, Guo M. Drosophila pink1 is required for mitochondrial function and interacts genetically with parkin. Nature. 2006 May 3; [Epub ahead of print]. PubMed citation
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Cookson MR. The biochemistry of Parkinson's disease. Annu Rev Biochem. 2005;74:2952. Review. PubMed citation
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Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. PubMed citation
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Hatano Y, Li Y, Sato K, Asakawa S, Yamamura Y, Tomiyama H, Yoshino H, Asahina M, Kobayashi S, Hassin-Baer S, Lu CS, Ng AR, Rosales RL, Shimizu N, Toda T, Mizuno Y, Hattori N. Novel PINK1 mutations in early-onset parkinsonism. Ann Neurol. 2004 Sep;56(3):424-7. Erratum in: Ann Neurol. 2004 Oct;56(4):603. PubMed citation
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Ibanez P, Lesage S, Lohmann E, Thobois S, De Michele G, Borg M, Agid Y, Durr A, Brice A; French Parkinson's Disease Genetics Study Group. Mutational analysis of the PINK1 gene in early-onset parkinsonism in Europe and North Africa. Brain. 2006 Mar;129(Pt 3):686-94. Epub 2006 Jan 9. PubMed citation
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Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. PubMed citation
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OMIM
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Park J, Lee SB, Lee S, Kim Y, Song S, Kim S, Bae E, Kim J, Shong M, Kim JM, Chung J. Mitochondrial dysfunction in Drosophila PINK1 mutants is complemented by parkin. Nature. 2006 May 3; [Epub ahead of print]. PubMed citation
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Rogaeva E, Johnson J, Lang AE, Gulick C, Gwinn-Hardy K, Kawarai T, Sato C, Morgan A, Werner J, Nussbaum R, Petit A, Okun MS, McInerney A, Mandel R, Groen JL, Fernandez HH, Postuma R, Foote KD, Salehi-Rad S, Liang Y, Reimsnider S, Tandon A, Hardy J, St George-Hyslop P, Singleton AB. Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease. Arch Neurol. 2004 Dec;61(12):1898-904. PubMed citation
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Samii A, Nutt JG, Ransom BR. Parkinson's disease. Lancet. 2004 May 29;363(9423):178393. Review. PubMed citation
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Silvestri L, Caputo V, Bellacchio E, Atorino L, Dallapiccola B, Valente EM, Casari G. Mitochondrial import and enzymatic activity of PINK1 mutants associated to recessive parkinsonism. Hum Mol Genet. 2005 Nov 15;14(22):3477-92. Epub 2005 Oct 5. PubMed citation
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Valente EM, Abou-Sleiman PM, Caputo V, Muqit MM, Harvey K, Gispert S, Ali Z, Del Turco D, Bentivoglio AR, Healy DG, Albanese A, Nussbaum R, Gonzalez-Maldonado R, Deller T, Salvi S, Cortelli P, Gilks WP, Latchman DS, Harvey RJ, Dallapiccola B, Auburger G, Wood NW. Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004 May 21;304(5674):1158-60. Epub 2004 Apr 15. PubMed citation
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Valente EM, Salvi S, Ialongo T, Marongiu R, Elia AE, Caputo V, Romito L, Albanese A, Dallapiccola B, Bentivoglio AR. PINK1 mutations are associated with sporadic earlyonset parkinsonism. Ann Neurol. 2004 Sep;56(3):336-41. PubMed citation
What Is the Official Name of the SNCA Gene?8 The official name of this gene is “synuclein, alpha (non A4 component of amyloid precursor).” 8
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=snca;jsessionid=BD942BD30D0E9A2D2CF316053BE92AD4.
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SNCA is the gene's official symbol. The SNCA gene is also known by other names, listed below.
What Is the Normal Function of the SNCA Gene? The SNCA gene provides instructions for making a small protein called alpha-synuclein. Alpha-synuclein is abundant in the brain, and smaller amounts are found in the heart, muscles, and other tissues. In the brain, alpha-synuclein localizes mainly at the tips of nerve cells (neurons) in specialized structures called presynaptic terminals. Within these structures, alpha-synuclein interacts with fats (lipids) and other proteins. Presynaptic terminals release chemical messengers, called neurotransmitters, from compartments known as synaptic vesicles. Although the function of alpha-synuclein remains unknown, several studies suggest that it plays an important role in maintaining a supply of synaptic vesicles in presynaptic terminals. It may also help regulate the release of dopamine. Dopamine is a type of neurotransmitter that is critical for controlling the start and stop of voluntary and involuntary movements.
What Conditions Are Related to the SNCA Gene? Parkinson Disease - Caused by Mutations in the SNCA Gene Researchers have described two types of alterations of the SNCA gene that cause early-onset Parkinson disease. One type of alteration changes one of the protein building blocks (amino acids) used to make alpha-synuclein. In some cases, the amino acid alanine is replaced with the amino acid threonine at protein position 53 (written as Ala53Thr) or with the amino acid proline at position 30 (written as Ala30Pro). In a few cases, the amino acid glutamic acid is replaced with the amino acid lysine at position 46 (written as Glu46Lys). These mutations cause the alpha-synuclein protein to misfold, or take on an incorrect 3-dimensional shape. In the other type of alteration, one of the two SNCA genes in each cell is inappropriately duplicated or triplicated. Instead of the normal two copies of the SNCA gene, each cell has three or four copies, which leads to an excess amount of alpha-synuclein.
Studies
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Other Disorders - Caused by Mutations in the SNCA Gene Researchers have described two types of alterations of the SNCA gene that cause early-onset Parkinson disease. One type of alteration changes one of the protein building blocks (amino acids) used to make alpha-synuclein. In some cases, the amino acid alanine is replaced with the amino acid threonine at protein position 53 (written as Ala53Thr) or with the amino acid proline at position 30 (written as Ala30Pro). In a few cases, the amino acid glutamic acid is replaced with the amino acid lysine at position 46 (written as Glu46Lys). These mutations cause the alpha-synuclein protein to misfold, or take on an incorrect 3-dimensional shape. In the other type of alteration, one of the two SNCA genes in each cell is inappropriately duplicated or triplicated. Instead of the normal two copies of the SNCA gene, each cell has three or four copies, which leads to an excess amount of alpha-synuclein.
Where Is the SNCA Gene Located? Cytogenetic Location: 4q21 Molecular Location on chromosome 4: base pairs 90,865,727 to 90,977,155
The SNCA gene is located on the long (q) arm of chromosome 4 at position 21. More precisely, the SNCA gene is located from base pair 90,865,727 to base pair 90,977,155 on chromosome 4.
References These sources were used to develop the Genetics Home Reference gene summary on the SNCA gene. •
Abou-Sleiman PM, Muqit MM, Wood NW. Expanding insights of mitochondrial dysfunction in Parkinson's disease. Nat Rev Neurosci. 2006 Mar;7(3):207-19. PubMed citation
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Bonini NM, Giasson BI. Snaring the function of alpha-synuclein. Cell. 2005 Nov 4;123(3):359-61. PubMed citation
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Cookson MR. The biochemistry of Parkinson's disease. Annu Rev Biochem. 2005;74:2952. Review. PubMed citation
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Farrer M, Kachergus J, Forno L, Lincoln S, Wang DS, Hulihan M, Maraganore D, GwinnHardy K, Wszolek Z, Dickson D, Langston JW. Comparison of kindreds with parkinsonism and alpha-synuclein genomic multiplications. Ann Neurol. 2004 Feb;55(2):174-9. PubMed citation
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Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. PubMed citation
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Golbe LI, Mouradian MM. Alpha-synuclein in Parkinson's disease: light from two new angles. Ann Neurol. 2004 Feb;55(2):153-6. No abstract available. PubMed citation
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Lim KL, Dawson VL, Dawson TM. The cast of molecular characters in Parkinson's disease: felons, conspirators, and suspects. Ann N Y Acad Sci. 2003 Jun;991:80-92. Review. PubMed citation
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Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. PubMed citation
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Norris EH, Giasson BI, Lee VM. Alpha-synuclein: normal function and role in neurodegenerative diseases. Curr Top Dev Biol. 2004;60:17-54. Review. PubMed citation
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OMIM: SNCA
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Pandey N, Schmidt RE, Galvin JE. The alpha-synuclein mutation E46K promotes aggregation in cultured cells. Exp Neurol. 2006 Feb;197(2):515-20. Epub 2005 Dec 1. PubMed citation
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Pankratz N, Foroud T. Genetics of Parkinson Disease. Neurorx. 2004 Apr;1(2):235-242. PubMed citation
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Polymeropoulos MH, Lavedan C, Leroy E, Ide SE, Dehejia A, Dutra A, Pike B, Root H, Rubenstein J, Boyer R, Stenroos ES, Chandrasekharappa S, Athanassiadou A, Papapetropoulos T, Johnson WG, Lazzarini AM, Duvoisin RC, Di Iorio G, Golbe LI, Nussbaum RL. Mutation in the alpha-synuclein gene identified in families with Parkinson's disease. Science. 1997 Jun 27;276(5321):2045-7. PubMed citation
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Sidhu A, Wersinger C, Vernier P. alpha-Synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson's disease. FEBS Lett. 2004 May 7;565(1-3):1-5. Review. PubMed citation
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Singleton AB, Farrer M, Johnson J, Singleton A, Hague S, Kachergus J, Hulihan M, Peuralinna T, Dutra A, Nussbaum R, Lincoln S, Crawley A, Hanson M, Maraganore D, Adler C, Cookson MR, Muenter M, Baptista M, Miller D, Blancato J, Hardy J, GwinnHardy K. alpha-Synuclein locus triplication causes Parkinson's disease. Science. 2003 Oct 31;302(5646):841. No abstract available. PubMed citation
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Tofaris GK, Spillantini MG. Alpha-synuclein dysfunction in Lewy body diseases. Mov Disord. 2005 Aug;20 Suppl 12:S37-44. PubMed citation
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Zarranz JJ, Alegre J, Gomez-Esteban JC, Lezcano E, Ros R, Ampuero I, Vidal L, Hoenicka J, Rodriguez O, Atares B, Llorens V, Gomez Tortosa E, del Ser T, Munoz DG, de Yebenes JG. The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia. Ann Neurol. 2004 Feb;55(2):164-73. PubMed citation
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What Is the Official Name of the GBA Gene?9 The official name of this gene is “glucosidase, beta; acid (includes glucosylceramidase).” GBA is the gene's official symbol. The GBA gene is also known by other names, listed below.
What Is the Normal Function of the GBA Gene? The GBA gene provides instructions for making an enzyme called beta-glucocerebrosidase. This enzyme is active in lysosomes, which are structures inside cells that act as recycling centers. Lysosomes use digestive enzymes to break down toxic substances, digest bacteria that invade the cell, and recycle worn-out cell components. Based on these functions, enzymes in the lysosome are sometimes called housekeeping enzymes. Betaglucocerebrosidase is a housekeeping enzyme that helps break down a large molecule called glucocerebroside into a sugar (glucose) and a simpler fat molecule (ceramide).
What Conditions Are Related to the GBA Gene? Gaucher Disease, Type 1 - Caused by Mutations in the GBA Gene More than 150 mutations in the GBA gene have been identified in people with type 1 Gaucher disease. Four mutations cause most cases of this disease in people of Ashkenazi (eastern and central European) Jewish ancestry. The most common mutation changes a single protein building block (amino acid) in the enzyme beta-glucocerebrosidase. Specifically, this mutation replaces the amino acid asparagine with the amino acid serine at position 370 in the enzyme (written as Asn370Ser or N370S). Gaucher Disease, Type 2 - Caused by Mutations in the GBA Gene More than 150 mutations in the GBA gene have been identified in people with type 1 Gaucher disease. Four mutations cause most cases of this disease in people of Ashkenazi (eastern and central European) Jewish ancestry. The most common mutation changes a single protein building block (amino acid) in the enzyme beta-glucocerebrosidase. Specifically, this mutation replaces the amino acid asparagine with the amino acid serine at position 370 in the enzyme (written as Asn370Ser or N370S). Gaucher Disease, Type 3 - Caused by Mutations in the GBA Gene About 70 mutations in the GBA gene have been found in people with type 2 Gaucher disease. Some of these genetic changes overlap with mutations that cause type 1 or type 3 Gaucher disease. Most of the GBA mutations responsible for type 2 Gaucher disease change single amino acids in beta-glucocerebrosidase, resulting in an unstable enzyme. This altered enzyme has severely reduced activity, and is unable to break down glucocerebroside properly. Deletions or rearrangements of genetic material in the GBA gene also occur
9
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=gba.
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frequently in type 2 Gaucher disease. These mutations result in the total absence of betaglucocerebrosidase in cells. Gaucher-Like Disease - Caused by Mutations in the GBA Gene About 45 GBA mutations have been identified in people with type 3 Gaucher disease. Some of these genetic changes overlap with mutations that cause type 1 or type 2 Gaucher disease. The most common cause of type 3 Gaucher disease is a mutation that substitutes the amino acid proline for the amino acid leucine at position 444 in beta-glucocerebrosidase (written as Leu444Pro). This mutation reduces the activity of the enzyme. As a result, glucocerebroside builds up in macrophages in the body's organs, leading to the signs and symptoms of this disease. Parkinson Disease - Associated with the GBA Gene The specific mutation responsible for Gaucher-like disease, which is an atypical form of Gaucher disease, substitutes the amino acid histidine for the amino acid aspartic acid at position 409 in beta-glucocerebrosidase (written as Asp409His or D409H). When this mutation is present in two copies of the GBA gene, it severely reduces the activity of the enzyme. As a result, glucocerebroside builds up in macrophages in the body's organs. This buildup causes the characteristic features of Gaucher-like disease including damage to the heart valves and the clear front surface of the eye (the cornea). Other Disorders - Associated with the GBA Gene Growing evidence suggests an association between GBA mutations and Parkinson disease or Parkinson-like disorders that affect movement and balance (parkinsonism). People with Gaucher disease have mutations in two copies of the GBA gene in each cell, while those with a mutation in just one copy of the gene are called carriers. Some studies suggest that carriers have an increased risk of developing Parkinson disease or parkinsonism. Symptoms of these disorders result from the loss of nerve cells that produce a chemical messenger called dopamine, which transmits signals within the brain to produce smooth physical movements. It remains unclear how GBA mutations lead to Parkinson disease or parkinsonism. Researchers speculate that GBA mutations may contribute to the faulty breakdown of toxic substances in nerve cells by impairing the function of lysosomes, or mutations may enhance the formation of abnormal protein deposits. As a result, toxic substances or protein deposits could accumulate and kill dopamine-producing nerve cells, leading to abnormal movements and balance problems.
Where Is the GBA Gene Located? Cytogenetic Location: 1q21 Molecular Location on chromosome 1: base pairs 153,470,866 to 153,481,111
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The GBA gene is located on the long (q) arm of chromosome 1 at position 21. More precisely, the GBA gene is located from base pair 153,470,866 to base pair 153,481,111 on chromosome 1.
References These sources were used to develop the Genetics Home Reference gene summary on the GBA gene. •
Aharon-Peretz J, Rosenbaum H, Gershoni-Baruch R. Mutations in the glucocerebrosidase gene and Parkinson's disease in Ashkenazi Jews. N Engl J Med. 2004 Nov 4;351(19):1972-7. PubMed citation
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Barranger JA, O'Rourke E. Lessons learned from the development of enzyme therapy for Gaucher disease. J Inherit Metab Dis. 2001;24 Suppl 2:89-96; discussion 87-8. Review. PubMed citation
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Charrow J, Andersson HC, Kaplan P, Kolodny EH, Mistry P, Pastores G, Prakash-Cheng A, Rosenbloom BE, Scott CR, Wappner RS, Weinreb NJ. Enzyme replacement therapy and monitoring for children with type 1 Gaucher disease: consensus recommendations. J Pediatr. 2004 Jan;144(1):112-20. Review. No abstract available. PubMed citation
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Cox TM. Gaucher disease: understanding the molecular pathogenesis of sphingolipidoses. J Inherit Metab Dis. 2001;24 Suppl 2:106-21; discussion 87-8. Review. PubMed citation
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Germain DP. Gaucher's disease: a paradigm for interventional genetics. Clin Genet. 2004 Feb;65(2):77-86. Review. PubMed citation
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Goker-Alpan O, Giasson BI, Eblan MJ, Nguyen J, Hurtig HI, Lee VM, Trojanowski JQ, Sidransky E. Glucocerebrosidase mutations are an important risk factor for Lewy body disorders. Neurology. 2006 Jun 21; [Epub ahead of print]. PubMed citation
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Jmoudiak M, Futerman AH. Gaucher disease: pathological mechanisms and modern management. Br J Haematol. 2005 Apr;129(2):178-88. Review. PubMed citation
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Lwin A, Orvisky E, Goker-Alpan O, LaMarca ME, Sidransky E. Glucocerebrosidase mutations in subjects with parkinsonism. Mol Genet Metab. 2004 Jan;81(1):70-3. PubMed citation
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Orvisky E, Park JK, Parker A, Walker JM, Martin BM, Stubblefield BK, Uyama E, Tayebi N, Sidransky E. The identification of eight novel glucocerebrosidase (GBA) mutations in patients with Gaucher disease. Hum Mutat. 2002 Apr;19(4):458-9. PubMed citation
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Pelled D, Trajkovic-Bodennec S, Lloyd-Evans E, Sidransky E, Schiffmann R, Futerman AH. Enhanced calcium release in the acute neuronopathic form of Gaucher disease. Neurobiol Dis. 2005 Feb;18(1):83-8. PubMed citation
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Sato C, Morgan A, Lang AE, Salehi-Rad S, Kawarai T, Meng Y, Ray PN, Farrer LA, St George-Hyslop P, Rogaeva E. Analysis of the glucocerebrosidase gene in Parkinson's disease. Mov Disord. 2005 Mar;20(3):367-70. PubMed citation
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Sidransky E. Gaucher disease: complexity in a "simple" disorder. Mol Genet Metab. 2004 Sep-Oct;83(1-2):6-15. Review. PubMed citation
What Is the Official Name of the SNCAIP Gene?10 The official name of this gene is “synuclein, alpha interacting protein (synphilin).” SNCAIP is the gene's official symbol. The SNCAIP gene is also known by other names, listed below.
What Is the Normal Function of the SNCAIP Gene? The SNCAIP gene provides instructions for making a protein called synphilin-1 and a slightly different version of this protein called synphilin-1A. These proteins are produced in the brain. They are usually located in specialized structures called presynaptic terminals, found at the tips of nerve cells. In nerve cells, synphilin-1 and synphilin-1A interact with another protein called alpha-synuclein. The functions of synphilin-1 and synphilin-1A, however, are unknown.
What Conditions Are Related to the SNCAIP Gene? Parkinson Disease - Associated with the SNCAIP Gene One SNCAIP mutation has been identified in a small number of people with Parkinson disease. This mutation leads to a change in one of the building blocks (amino acids) used to make synphilin-1. Specifically, the amino acid arginine is replaced by the amino acid cysteine at position 621 in the protein's chain of amino acids (written as Arg621Cys or R621C).
Where Is the SNCAIP Gene Located? Cytogenetic Location: 5q23.1-q23.3 Molecular Location on chromosome 5: base pairs 121,675,718 to 121,827,692
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Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=sncaip;jsessionid=BD942BD30D0E9A2D2CF316053BE92AD4.
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The SNCAIP gene is located on the long (q) arm of chromosome 5 between positions 23.1 and 23.3. More precisely, the SNCAIP gene is located from base pair 121,675,718 to base pair 121,827,692 on chromosome 5.
References These sources were used to develop the Genetics Home Reference gene summary on the SNCAIP gene. •
Chung KK, Zhang Y, Lim KL, Tanaka Y, Huang H, Gao J, Ross CA, Dawson VL, Dawson TM. Parkin ubiquitinates the alpha-synuclein-interacting protein, synphilin-1: implications for Lewy-body formation in Parkinson disease. Nat Med. 2001 Oct;7(10):1144-50. PubMed citation
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Eyal A, Szargel R, Avraham E, Liani E, Haskin J, Rott R, Engelender S. Synphilin-1A: An aggregation-prone isoform of synphilin-1 that causes neuronal death and is present in aggregates from {alpha}-synucleinopathy patients. Proc Natl Acad Sci U S A. 2006 Apr 4; [Epub ahead of print]. PubMed citation
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Kruger R. The role of synphilin-1 in synaptic function and protein degradation. Cell Tissue Res. 2004 Oct;318(1):195-9. Epub 2004 Aug 19. PubMed citation
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Lee G, Junn E, Tanaka M, Kim YM, Mouradian MM. Synphilin-1 degradation by the ubiquitin-proteasome pathway and effects on cell survival. J Neurochem. 2002 Oct;83(2):346-52. PubMed citation
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Lim KL, Dawson VL, Dawson TM. The cast of molecular characters in Parkinson's disease: felons, conspirators, and suspects. Ann N Y Acad Sci. 2003 Jun;991:80-92. Review. PubMed citation
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Marx FP, Holzmann C, Strauss KM, Li L, Eberhardt O, Gerhardt E, Cookson MR, Hernandez D, Farrer MJ, Kachergus J, Engelender S, Ross CA, Berger K, Schols L, Schulz JB, Riess O, Kruger R. Identification and functional characterization of a novel R621C mutation in the synphilin-1 gene in Parkinson's disease. Hum Mol Genet. 2003 Jun 1;12(11):1223-31. PubMed citation
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Pankratz N, Foroud T. Genetics of Parkinson Disease. Neurorx. 2004 Apr;1(2):235-242. PubMed citation
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What Is the Official Name of the UCHL1 Gene?11 The official name of this gene is “ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase).” UCHL1 is the gene's official symbol. The UCHL1 gene is also known by other names, listed below.
What Is the Normal Function of the UCHL1 Gene? The UCHL1 gene provides instructions for making an enzyme called ubiquitin carboxylterminal esterase L1. This enzyme is found in nerve cells throughout the brain. Ubiquitin carboxyl-terminal esterase L1 is probably involved in the cell machinery that breaks down (degrades) unwanted proteins. In cells, damaged or excess proteins are tagged with molecules called ubiquitin. Ubiquitin serves as a signal to move these unwanted proteins into specialized structures known as proteasomes, where the proteins are degraded. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. Although the exact function of ubiquitin carboxyl-terminal esterase L1 is not fully understood, it appears to have two enzyme activities. One activity, called hydrolase, removes and recycles ubiquitin molecules from degraded proteins. This recycling step is important to sustain the degradation process. The other enzyme activity, known as ligase, links together ubiquitin molecules for use in tagging proteins for disposal.
What Conditions Are Related to the UCHL1 Gene? Parkinson Disease - Associated with the UCHL1 Gene A normal variation (polymorphism) in the UCHL1 gene appears to reduce the risk of developing Parkinson disease, particularly in young adults. This variation leads to a change in one of the building blocks (amino acids) used to make the UCHL1 enzyme. Instead of serine at position 18 in the enzyme's chain of amino acids, people with the protective polymorphism have the amino acid tyrosine. This amino acid variation is written as Ser18Tyr or S18Y. This particular variation is very common in Chinese and Japanese populations and occurs less frequently in European populations. The polymorphism reduces the ligase activity of the UCHL1 enzyme but has little effect on the hydrolase activity. It remains unclear how this amino acid variation protects against Parkinson disease.
Where Is the UCHL1 Gene Located? Cytogenetic Location: 4p14 Molecular Location on chromosome 4: base pairs 40,953,685 to 40,965,202 11
Adapted from the Genetics Home Reference of the National Library of Medicine: http://ghr.nlm.nih.gov/gene=uchl1.
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The UCHL1 gene is located on the short (p) arm of chromosome 4 at position 14. More precisely, the UCHL1 gene is located from base pair 40,953,685 to base pair 40,965,202 on chromosome 4.
References These sources were used to develop the Genetics Home Reference gene summary on the UCHL1 gene. •
Facheris M, Strain KJ, Lesnick TG, de Andrade M, Bower JH, Ahlskog JE, Cunningham JM, Lincoln S, Farrer MJ, Rocca WA, Maraganore DM. UCHL1 is associated with Parkinson's disease: a case-unaffected sibling and case-unrelated control study. Neurosci Lett. 2005 Jun 10-17;381(1-2):131-4. Epub 2005 Feb 25. PubMed citation
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Gasser T. Genetics of Parkinson's disease. Curr Opin Neurol. 2005 Aug;18(4):363-9. PubMed citation
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Lim KL, Dawson VL, Dawson TM. The cast of molecular characters in Parkinson's disease: felons, conspirators, and suspects. Ann N Y Acad Sci. 2003 Jun;991:80-92. Review. PubMed citation
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Liu Y, Fallon L, Lashuel HA, Liu Z, Lansbury PT Jr. The UCH-L1 gene encodes two opposing enzymatic activities that affect alpha-synuclein degradation and Parkinson's disease susceptibility. Cell. 2002 Oct 18;111(2):209-18. PubMed citation
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Maraganore DM, Lesnick TG, Elbaz A, Chartier-Harlin MC, Gasser T, Kruger R, Hattori N, Mellick GD, Quattrone A, Satoh J, Toda T, Wang J, Ioannidis JP, de Andrade M, Rocca WA; UCHL1 Global Genetics Consortium. UCHL1 is a Parkinson's disease susceptibility gene. Ann Neurol. 2004 Apr;55(4):512-21. Erratum in: Ann Neurol. 2004 Jun;55(6):899. Toda, Taksushi [corrected to Toda, Tatsushi]. PubMed citation
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Morris HR. Genetics of Parkinson's disease. Ann Med. 2005;37(2):86-96. Review. PubMed citation
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Pankratz N, Foroud T. Genetics of Parkinson Disease. Neurorx. 2004 Apr;1(2):235-242. PubMed citation
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Toda T, Momose Y, Murata M, Tamiya G, Yamamoto M, Hattori N, Inoko H. Toward identification of susceptibility genes for sporadic Parkinson's disease. J Neurol. 2003 Oct;250 Suppl 3:III40-3. PubMed citation
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Wintermeyer P, Kruger R, Kuhn W, Muller T, Woitalla D, Berg D, Becker G, Leroy E, Polymeropoulos M, Berger K, Przuntek H, Schols L, Epplen JT, Riess O. Mutation analysis and association studies of the UCHL1 gene in German Parkinson's disease patients. Neuroreport. 2000 Jul 14;11(10):2079-82. PubMed citation
Federally Funded Research on Parkinson Disease The U.S. Government supports a variety of research studies relating to Parkinson disease. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.12 CRISP (Computerized Retrieval of Information on Scientific Projects) CRISP is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Parkinson disease. 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 Parkinson disease. The following is typical of the type of information found when searching the CRISP database for Parkinson disease: •
Project Title: ABNORMAL GENE EXPRESSION IN PD Principal Investigator & Institution: Greene, Lloyd A.; Professor; Columbia University Health Sciences Columbia University Medical Center New York, Ny 100323702 Timing: Fiscal Year 2005 Summary: This project's overall goal is to identify genes that undergo abnormal levels of expression in neurons affected by Parkinson Disease (PD) and that contribute to their death. The rationale is that neuron death in models of PD and other neurodegenerations requires transcription-dependent gene regulation. Once such genes are recognized and their causal roles in neuron death established, they will become potential targets for preventive/ameliorative therapy in PD. During the last period, we used SAGE to detect approximately 1,200 transcripts (out of 14,000) that are significantly up-regulated in a cell culture PD model. Among other findings, the SAGE profile revealed that PD mimetics induce an endoplasmic reticulum stress response that may contribute to death. For the next period, we propose the following specific aims: 1 To continue to "mine" our SAGE data of 6-OHDA responsive genes. Bioinformatics will be used to match additional SAGE tags to known transcripts and to provide updated assessments of the potential functional roles of the regulated genes in neuronal death and/or PD. 2. To
12 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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continue studies of the functional roles of select 6-OHDA-responsive genes identified by SAGE. Gene selection will reflect deduced potential relevance to PD and neuron death. Initial emphasis will be on ER stress genes and in particular on the pro-apoptotic transcription factor CHOP. Eight additional regulated genes have been chosen for initial emphasis. Studies will include loss- and gain-of-function experiments with PC12 cells and sympathetic neurons cultured from wild-type and mutant mice. When suitable animal models (null or transgenic) become available, these will be exploited with our collaborators Drs. Burke and Przedborski. 3. To continue examining whether responsive genes detected in our SAGE study are also up-regulated in animals models of PD and in PD tissue. Animal models will be examined collaboratively with Drs. Burke and Przedborski. PD and control tissue will be examined by a) immmunohistochemistry of SNpc and sympathetic neurons (SCG) and b) by quantitative PCR using RNA from such neurons harvested by laser capture microdissection. 4. To use data generated by SAGE or MPSS of control and PD neurons to detect additional regulated transcripts for studies of causal roles in neuronal death in PD. This longer-range aim that will seek to exploit gene profiling of control and PD neurons. Comparison of profiles from SCG, SNpc and PC12 cells will provide a powerful filter for identification of genes for functional in vitro and in vivo analyses as described above. •
Project Title: CLINICAL CENTER FOR NEUROPROTECTION IN PARKINSON DISEASE Principal Investigator & Institution: Dewey, Richard B.; Neurology; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2005; Project Start 15-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Parkinson’s disease is an inexorably progressive disorder of unknown cause in which neurons of the substantial nigra progressively degenerate resulting in ever-greater degrees of brain dopamine deficiency. While a number of treatments have been developed that improve the neurochemical deficit, no treatment has been demonstrated to ameliorate the neuronal deterioration. Such a neuroprotective effect is highly desirable because if this could be achieved, a significant delay in clinical deterioration of patients could be realized. The proposal outlined here aims to establish a Clinical Center for neuroprotective research at UT Southwestern Medical Center which will cooperate with up to 42 other such centers around the country in the development and execution of a large-scale clinical trial to test one or more potentially neuroprotective agents for Parkinson’s disease. The Clinical Center for Movement Disorders at UT Southwestern Medical Center in Dallas, TX is well suited to becoming such a Clinical Center. It is the primary academic referral center for North Texas and its two staff neurologists are experienced in the design, conduct, and reporting of clinical trials in Parkinson’s disease. Once the Clinical Centers are designated, a series of pilot studies will be conducted first to identify the most promising agent or agents. Subsequently, a large trial involving several thousand patients will be developed and conducted to establish whether the chosen agent is actually capable of slowing down the progression of this disease. By studying such a large number of patients under rigorously blinded and controlled conditions, it should be possible to identify even a small beneficial effect on disease progression which would nevertheless be very important, not only for the implications on retarding disease progression, but also because observing such an effect might yield insights into the underlying pathogenesis of this common and disabling disease.
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Project Title: CLINICAL CENTER FOR NEUROPROTECTION CLINICAL TRIAL
THE
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Principal Investigator & Institution: Chou, Kelvin L.; Memorial Hospital of Rhode Island 111 Brewster St Pawtucket, Ri 028604400 Timing: Fiscal Year 2006; Project Start 01-JUN-2006; Project End 30-NOV-2009 Summary: (provided by applicant): The goal of this proposal is to participate as a clinical site in exploratory trials of neuroprotective agents for patients with early Parkinson’s disease (PD). Current therapies for PD address the symptoms, but do not alter the course of the disease. However, a number of new compounds have been identified that have the potential to slow down or even halt the progression of PD. If any of these compounds can truly protect viable neurons from degenerating, they would delay or even prevent significant disability in the millions of patients who suffer from PD. Our primary objective with this project will be to recruit and retain at least 2 research subjects per month. For the remaining exploratory neuroprotection trials, and the subsequent large simple trial. The Parkinson's Disease and Movement Disorders Center (PDMDC) at Memorial Hospital of Rhode Island (MHRI) employs a staff of highly qualified investigators and coordinators with extensive experience (over 35 years in total) in the design and conduct of clinical trials in PD. Our center has consistently recruited PD patients for research studies over many years. We recruit particularly well for the early PD clinical trials, meeting or exceeding expected quotas in each trial needing de novo, untreated PD patients. We are the only movement disorders center in the state of Rhode Island, and see patients from all over Rhode Island and southeastern New England. Our patients do not like to travel far for their medical care, and are unlikely to go to other large movement disorders centers. They are extremely compliant with study protocols, and have a strong interest in participating in clinical studies. We have strong ties with the American Parkinson Disease Association (APDA) Rhode Island Chapter, which is the largest PD advocacy group in the region. The APDA chapter is extremely active and supportive of our endeavors and the APDA's information and Referral (I&R) Center is an intrinsic part of the PDMDC. The I&R Center is responsible for regional education and support, including coordination of support groups. Rhode Island is also home to a large Hispanic and female population, making it relatively easy for us to recruit minorities and women into the study. Because of our track record in recruiting for similar trials, our close connections with local advocacy groups, and our referral population (comprised of a large group of ethnic minorities and women), we believe that we are qualified to serve as a clinical center for the PD neuroprotection trials. •
Project Title: CROSSED GENETIC RISK OF ALZHEIMER AND PARKINSON DISEASE Principal Investigator & Institution: Levey, Allan I.; Professor; Emory University 1784 North Decatur Road, Suite 510 Atlanta, Ga 30322 Timing: Fiscal Year 2005; Project Start 01-JUN-2005; Project End 31-MAR-2010 Summary: Alzheimer's disease (AD) and Parkinson’s disease (PD) are generally considered separate disease entities. However, there is extensive overlap among the clinical and pathologic features, indicating that common mechanisms contribute to neurodegeneration in these disorders. Our preliminary studies from both Emory and Iceland reveal a significantly increased crossed familial risk of AD and PD, suggesting that there are common genetic predispositions in "sporadic" late-onset cases of both diseases. Capitalizing on the ability to examine extended pedigrees in Iceland in collaboration with deCODE Genetics, our exciting preliminary findings demonstrate
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novel loci associated with both AD and PD., In the proposed collaborative studies between Emory and deCODE Genetics, we test our central hypothesis that a novel susceptibility gene on chromosome 7p contributes to both AD and PD risk in the Emory ADC subjects, and is more strongly associated with those cases with overlapping cognitive and extrapyramidal features. In specific aim 1, we test the association of candidate genes at the chromosome 7p locus with AD subjects in a case-control study using subjects in the Emory ADC. In specific aim 2, we test the association of candidate genes at the chromosome 7p locus with PD subjects in a case-control study using subjects in the Emory Parkinson's Disease Center. In specific aim 3, we propose to perform detailed genotype-phenotype correlations in the Emory AD and PD subjects to understand more precisely the role of the chromosome 7p locus in the clinical manifestations of AD and PD. Together, these aims will test our central hypothesis and advance our understanding of the complex genetics of AD, PD, and overlap syndromes. •
Project Title: DEPRESSION DIAGNOSIS AND TREATMENT IN PARKINSON DISEASE Principal Investigator & Institution: Weintraub, Daniel; Psychiatry; University of Pennsylvania Office of Research Services Philadelphia, Pa 19104 Timing: Fiscal Year 2005; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by candidate): This grant application on behalf of Daniel Weintraub, MD, Assistant Professor of Psychiatry at the University of Pennsylvania, is for the Mentored Patient-Oriented Research Career Development Award,(K23). The focus of this award is to enable Dr. Weintraub (PI) to acquire the academic and research expertise to achieve his career goal of becoming an independent researcher in the assessment and treatment of the psychiatric complications of Parkinson’s disease (PD), an area in which there is an urgent need for clinical research due to a lack of consensus over phenomenology and the lack of empirical evidence to support current treatment practice. The research plan for this award will in part involve conducting a depression screening and assessment process in two PD specialty care settings in order to determine demographic, psychiatric, neurologic, and cognitive correlates of depression and to propose modified criteria for affective disorders in PD. In conjunction with this, the PI will conduct an open-label antidepressant study using escitalopram to determine response rates under treatment as a function of different diagnostic criteria and to identify moderators of response under treatment. The impact of antidepressant treatment on comorbid psychiatric and cognitive symptoms, motor symptoms, quality of life, and caregiver burden will also be probed. Identification of modifiers of treatment response will help inform future studies and clinical decision-making. The career development plan will revolve around the acquisition of skills related to Dr. Weintraub becoming a research geriatric- and neuro-psychiatrist with expertise in Parkinson’s disease and proficient in conducting intervention research in this area. The specific skill areas to be developed during the course of the proposed award relate to: (1) intervention research and biostatistics; (2) clinical neuroscience; and (3) the neurology of Parkinson’s disease (PD). Methods of career development include: (1) the proposed research study; (2) the mentorship of Drs. Ira Katz and Matthew Stern; (3) consultation with experts in assessment and treatment of geriatric depression and neuropsychiatric disease; (4) formal coursework in clinical trials research, biostatistics, clinical neuroscience, and neurology; (5) training in the assessment and treatment of Parkinson’s disease (6) attendance at scientific meetings; and (7) mentored data analysis and manuscript preparation.
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Project Title: EFFECTS OF COENZYME Q10 IN PARKINSON DISEASE-PHASE 3 Principal Investigator & Institution: Beal, M Flint.; Professor; Neurology and Neuroscience; Weill Medical College of Cornell Univ 1300 York Avenue New York, Ny 10021 Timing: Fiscal Year 2005; Project Start 30-SEP-2005; Project End 30-NOV-2009 Summary: (provided by applicant): Parkinson's Disease (PD) is a progressive, neurodegenerative disease, which affects over 1,000,000 Americans. In an NIHsupported phase II trial, our group demonstrated that treatment of patients with early, untreated PD with high dosages of coenzyme Q10 (300, 600 and 1200 mg/d) was safe and well tolerated and that there was a positive trend for treatment to slow the progressive impairment as measured by the Unified Parkinson Disease Rating Scale (UPDRS). In pre-specified secondary analyses, we noted that the highest dosage of coenzyme Q10 was the most effective dosage and that treatment with coenzyme Q10 helped the PD patients maintain independence, as measured by Schwab and England Scale. In the proposed study, we will conduct a prospective, randomized, and placebocontrolled, double-blind phase clinical trial of coenzyme Q10 to attempt to confirm and extend the results of our phase II study. We propose to enroll 600 subjects who have early PD and do not yet require treatment with dopaminergic agents. Subjects will be randomly assigned to receive placebo, coenzyme Q10 1200 mg/d or 2400 mg/d, evaluated at screening, baseline, months 1, 4, 8, 12, and 16 visits and assessed with the UPDRS. The investigator will determine whether the subject has reached disability requiring treatment with a dopaminergic agent. Our primary analysis will undertake to confirm the benefit found in our phase II study by analyzing the change in total UPDRS score to the point that the subjects reach disability requiring treatment with a dopaminergic agent or to the 16 month visit. We will also analyze the Schwab and England Scale and the PD Quality of Life Scale data collected to the point that the subjects reach disability requiring treatment with a dopaminergic agent or to the 16 month visit. We will determine the mean plasma coenzyme Q10 levels at baseline and at visits 1, 8 and 16 months, and determine whether the mean correlates with reduction in worsening of the total UPDRS score.
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Project Title: EMORY UNIVERSITY PD NEUROPROTECTION CLINICAL TRIAL CENTER Principal Investigator & Institution: Juncos, Jorge L.; Neurology; Emory University 1784 North Decatur Road, Suite 510 Atlanta, Ga 30322 Timing: Fiscal Year 2006; Project Start 17-MAY-2006; Project End 30-NOV-2010 Summary: (provided by applicant): The Emory University Movement Disorders Program and the Comprehensive Parkinson's Disease Center has proven to have in place the necessary resources and infrastructure to continue to be a Parkinson's Disease Neuroprotection Clinical Trial Center. We have experience in conducting neuroprotective trials and are in fact already participating in the NET-PD Futility Study 2 trial as a subcontractor to University of Alabama in Birmingham (UAB). The aim of this proposal in to revert our center from a subcontracting site to its original status as an independent site. We have been a successful site in this and many other studies in part because of the estimated 50,000 persons currently diagnosed with Parkinson’s disease in our region and the estimated 5,000 patients that are newly diagnosed each year in our region. The demographic characteristics of the area served by Emory University allows for the recruitment of an ethnically diverse population of study patients. The Emory University programs involved in the research and treatment of Parkinson's Disease have the necessary space to comfortably and efficiently conduct clinical trials, prepare and
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process lab specimens and securely and confidentially maintain study medication and documentation. An experienced clinical trial team is currently in place to assure that the studies are conducted in a manner which allows for the accurate, efficient and timely collection of data. The Clinical Trial Staff have all received training and certification to conduct clinical trials from the Emory University Institutional Review Board and have been trained and currently follow Good Clinical Practice Guidelines to assure the safety and protection of study participants. The Principal Investigator, Dr. Jorge L. Juncos, has extensive experience in developing, conducting and monitoring clinical trials and an excellent track record in the recruitment of patients. The Center currently works closely with the American Parkinson Disease Association of Georgia to inform and recruit new patients for these studies. In conclusion this proposal should evidence the fact that our center has demonstrated is capacity for serving as an excellent investigative and recruitment site for these NIH sponsored trials in neuroprotection in PD. •
Project Title: EXPIRATORY PARKINSON'S
MUSCLE
TRAINING
IN
PATIENTS
WITH
Principal Investigator & Institution: Sapienza, Christine M.; Professor and Chair; Communication Sci & Disorders; University of Florida 219 Grinter Hall Gainesville, Fl 32611 Timing: Fiscal Year 2005; Project Start 01-JAN-2005; Project End 31-DEC-2006 Summary: This project tests the outcome of a novel training method for strengthening the muscles of the respiratory system. Targeting the expiratory muscles, the technique is referred to as expiratory muscle strength training (EMST). EMST provides the user with an experimental high-pressure threshold device which places a high physiological load on the muscles during breathing. The treatment lasts 4 weeks and the majority of the training takes place in the person's home. We intend to test the outcome of EMST in a group of individuals with idiopathic Parkinson disease (IPD). Parkinson’s disease is a debilitating disease with well-recognized adverse effects on motor function including breathing, cough, swallow and speech. The general purpose of this research is to first determine if those with a specific severity of IPD can improve expiratory muscle strength and secondly to determine what outcome variables are affected by the improvements in expiratory muscle strength. We anticipate improvements in breathing, cough, swallow and speech following treatment that are attributable to the training technique. Study of three groups of 30 subjects with Hoehn & Yahr, stage I-III IPD in a treatment, sham and control group will define the therapeutic effect of this technique. Quantitative measures include measures of volume, flow, sound pressure level and videoflourographic indices as well as listener perception tests to determine the technique's impact on overall sound quality and speech intelligibility. Results from this project will provide new information about the EMST program as a novel technique. The goals of the grant meet the mission of the R21. Its potential impact is high due to the therapy program's innovative nature and potential cost-effectiveness as a treatment approach. •
Project Title: GENETIC ANALYSIS OF PARKINSONISM IN AN OHIO AMISH FAMILY Principal Investigator & Institution: Lee, Stephen Luming.; Medicine; Dartmouth College Office of Sponsored Projects Hanover, Nh 03755 Timing: Fiscal Year 2005; Project Start 15-SEP-2003; Project End 31-AUG-2008 Summary: (provided by applicant): Disease genes discovered through linkage analysis in familial Parkinson disease (PD) are yielding new insights into the pathogenesis of
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this neurodegenerative disorder. However, the known genes explain only a minor portion of all PD, and the chromosomal regions linked to other families are large and contain numerous genes. The discovery of additional hereditary causes of PD may help further elucidate the underlying etiopathogenesis and provide new pharmacological targets. It is therefore crucial that additional families are characterized. In an extended Amish family in northeastern Ohio, clinical information for familial Parkinsonism has been obtained. To test the hypothesis that genetic influences contribute to the expression of Parkinsonism in this Amish pedigree, the immediate aims of this project are threefold: 1) to fully ascertain the disease phenotype of the affected individuals, through genealogical data, clinical history, medical records, and neurological exam, 2) to identify the genetic locus or loci associated with the disease phenotype, initially by evaluating previously identified genetic loci, and conducting a genome-wide scan using conventional linkage analysis, transcript mapping, and gene identification, and 3) to perform candidate gone analysis to test whether specific gene modifiers enhance or suppress the expression of the disease phenotype. The candidate's long-term goals are to apply well-established and emerging methods toward understanding the genetic basis of Parkinsonism. This grant will help the candidate establish an independent career in academic neurology with specialization in movement disorders and neurogenetics by allowing the candidate 1) to evaluate and treat patients in a movement disorders clinic under the guidance of Thomas L. Davis, M.D., and 2) to learn the laboratory, statistical, and computational methods of genetic epidemiology. This will be accomplished through conduct of the proposed research project and participation in formal courses under the guidance of the candidate's mentor, Jonathan L. Haines, Ph.D. •
Project Title: GENETICS OF PARKINSON DISEASE IN THE AMISH Principal Investigator & Institution: Racette, Brad A.; Neurology; Washington University 1 Brookings Dr, Campus Box 1054 Saint Louis, Mo 631304899 Timing: Fiscal Year 2005; Project Start 15-MAY-2002; Project End 30-APR-2007 Summary: The applicant is a neurologist and movement disorders specialist with three years of post-fellowship, faculty experience involving clinical care, clinical trials, and clinical research into etiologic risk factors for PD including genetic factors. The goal of this career development award is to provide the applicant with comprehensive training in genetic epidemiology through course work, individual tutorials, and practical application of gene mapping techniques to a multi-incident Amish family with Parkinson Disease (PD). PD is a neurodegenerative disorder that produces substantial disability for nearly 1 million people in North America. There is no known cause of the disease in the majority of patients; however, a genetic etiology has been found in a few rare multi-incidence families. Identification of such genes and subsequent determination of the cell biological effects of these mutations will provide important clues to the pathophysiology. Each new mutation discovered adds critical converging evidence about pathophysiological mechanisms common to all to those affected with PD. We have identified 27 members of a large Amish family with clinically typical PD and have excluded known PD genetic mutations. However, we still need to prove that PD is inherited in this pedigree. We will use two different methods to prove that PD in this kindred has a genetic basis. The first approach will assume an autosomal recessive model of inheritance and use genetic marker data provided by CIDR on our subjects to perform homozygosity mapping. A second approach will be to calculate a kinship coefficient to determine if the affected members of the pedigree are "more related" than randomly selected age-matched individuals from the same population. Finally, we will test whether [18]FDOPA PET permits the conversion of some people identified clinically as possible or probable PD in to PET-confirmed PD and thereby functioning as an
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endophenotype for disease state. This family provides a unique opportunity for the candidate to become a productive independent investigator in genetics of Parkinson Disease and other movements disorders and to develop skills needed for interpretation of [18]FDOPA PET. •
Project Title: IN VIVO AMYLOID AND DEMENTIA IN SYNUCLEIONOPATHIES Principal Investigator & Institution: Moore, Robert Y.; Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2005; Project Start 01-DEC-2004; Project End 30-NOV-2009 Summary: Synucleinopathies are now recognized as major causes of dementia. The principal synucleinopathies are the overlapping clinical entities of Parkinson disease (PD), including Parkinson disease with dementia (PDD), and dementia with Lewy bodies (DLB). PDD and DLB are the most common causes of dementia after Alzheimer disease (AD). A clinical distinction between PDD and DLB, and distinguishing them from AD, is often difficult and, perhaps more importantly, the clinician encounters many situations in which it is unclear from clinical data and structural imaging whether a dementia reflects predominantly a single process or a complex one with Alzheimer changes coexisting with one or more of the other pathologies. In addition, as more specific therapies become available, it will be important to have methods to distinguish among the contributing pathological processes. The intent of this project is to use amyloid PET (PIB PET) combined with Clinical and neuropsychological evaluation, fluorodeoxyglucose (FDG) PET and dopamine transporter PET (in DLB ) to determine the contribution of amyloid deposition to dementia in PD and DLB. The specific aims are as follows: 1) to perform PIB PET in DLB and PDD subjects that have been carefully characterized with respect to clinical features, changes on structural MRI, PD rating scales, neuropsychological performance, FDG PET and DAT PET (DLB); 2) to perform PIB PET at study entry and after 3 years in PD subjects characterized at both time points with respect to clinical features, PD rating scales, changes on structural MRI, neuropsychological performance and FDG PET. The overall objectives of the project are to determine the following: 1) the contribution of beta-amyloid accumulation to the dementia in PDD and DLB; 2) the role of beta-amyloid accumulation in the conversion of PD to PDD; 3) the contribution of FDG, PIB PET and dopamine transporter PET, correlated with clinical evaluation, neuropsychological testing and structural imaging, to understanding the pathophysiology of dementia associated with synucleinopathies.
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Project Title: INCREASE ACCESS TO TRAINING IN EFFICACIOUS SPEECH THERAPY THROUGH TECHNOLOGY Principal Investigator & Institution: Fox, Cynthia M.; Gleeco, Llc 1222 Wildwood Cir Boulder, Co 80305 Timing: Fiscal Year 2006; Project Start 01-MAY-2006; Project End 31-MAR-2007 Summary: (provided by applicant): Project Summary: We propose to develop and evaluate a DVD training program for teaching speech therapists an efficacious speech treatment (LSVT) for Parkinson disease (PD). LSVT is a proven efficacious speech treatment program that restores oral communication in people with PD beyond what current pharmacological and surgical interventions can offer. A critical problem is that the vast majority of people who could benefit from this treatment do not have access to LSVT trained speech therapists. Thus, patients suffer unnecessarily with disordered communication. The current LSVT training program for speech therapists (live two day training) affords access to only a limited number of speech therapists. This Phase 1 work proposes to develop, administer and evaluate an innovative DVD Training and
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Parkinson Disease
Certification Program to teach speech therapists to deliver LSVT. It is expected that the proposed DVD training program will be shown to be feasible and effective, and produce the same quality training as the current live two day trainings. Successful outcomes of the proposed project will directly support Phase II goals for expanding DVD product lines and expanding the DVD training channel to include ongoing research updates, multi- lingual training, advances in technology supported LSVT. The outcomes of this project will drive innovative training mechanisms to improve quality of speech therapy training by providing a more feasible and efficient transfer of knowledge from the research lab to clinical practice, while supporting development of a commercially viable product line. Relevance: Although nearly 90% people with Parkinson disease have a speech or voice problem, which can negatively impact quality of life, only 4% receive speech treatment. The proposed work will benefit the health and well-being of these individuals by increasing access to speech therapists who are trained to administer a speech treatment (LSVT) that is known to be effective in improving speech and voice in people with Parkinson disease. The long-term vision for this proposed work is to make LSVT available to all who could benefit worldwide •
Project Title: MASKED FACES IN PARKINSON DISEASE: MECHANISM & TREATMENT Principal Investigator & Institution: Bowers, Dawn; Associate Professor; Clinical & Health Psychology; University of Florida 219 Grinter Hall Gainesville, Fl 32611 Timing: Fiscal Year 2005; Project Start 15-DEC-2004; Project End 30-NOV-2008 Summary: (provided by applicant): The overall goal of this research is to improve understanding of nonverbal communication disorders among patients with neurologic disease. Facial expressions are complex signals that are brief, last only a few minutes and important for communicating intention, motivation, and emotional states. In humans a variety of neurologic and psychiatric conditions alter the propensity to use facial signals. In fact, diminished facial expressivity, or the "masked face" is one of the cardinal features of Parkinson’s disease, a neurodegenerative basal ganglia disorder that primarily affects older adults. Classically, it has been held that Parkinson’s disease represents a "model system" for impairing spontaneous (limbic) facial emotions, whilst leaving intentionally posed (cortical) facial expressions intact. Preliminary data, using computer imaging methods to quantify dynamic movement changes over the face, tentatively suggests that this dissociation may be unfounded (Bowers et al., in press). The purpose of the proposed research is to apply computing imaging methods to learn: (a) whether diminished facial expressivity among Parkinson patients involves modulatory defects that influence both volitional and spontaneous emotions; (b) whether these modulatory defects are related to dopaminergic deficiency, and (c) which parameters of facial expressivity (timing, frequency, entropy) are improved by a behavioral intervention for treating respiratory strength in PD. Taken together, the findings from this study may facilitate understanding of the mechanisms underlying diminished facial expressivity in Parkinson’s disease and provide information that may ultimately be useful in the treatment of nonverbal communication disturbances.
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Project Title: MICHIGAN STATE UNIVERSITY PARKINSON DISEASE CLINICAL CENTER Principal Investigator & Institution: Goudreau, John L.; Assistant Professor; Neurology and Epidemiology; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2006; Project Start 17-MAY-2006; Project End 30-NOV-2010
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Summary: (provided by applicant): This is an application for the Michigan State University (MSU) Department of Neurology to become a clinical center in the Parkinson Disease Neuroprotection Clinical Trial consortium. The objective of the this clinical trial is demonstrate the efficacy of one or several neuroprotective agents in slowing the progression of Parkinson Disease (PD) in a large, double blind, placebo-controlled clinical trial. The MSU Parkinson Disease Clinical Center will identify, enroll, and maintain patients with mild, early PD (Hoehn and Yahr < 2, within 5 years of symptom onset) in the pilot and Phase III trial components of this multicenter clinical trial. This proposal documents the outstanding patient recruitment and retention potential of the experienced clinical staff at MSU. Collectively, the primary investigators and the Department of Neurology at MSU have an average of nearly 700 PD patient visits and see approximately 125 new PD patients per year. Based on data from direct chart review, 55% of the new patients would meet the inclusion and exclusion criteria if patients taking symptomatic medications are included; 20% would meet criteria if those taking symptomatic medications were excluded. The large pool of potentially eligible cases reflects the referral pattern for the Department of Neurology at MSU, which is the focus of primary and secondary referrals from a large area of the state that is relatively underserved by other neurologists. The central location of MSU within the state of Michigan, combined with the dispersed statewide medical school campus system, is ideal for maximal patient recruitment. Established relationships with area neurologists, local support groups and with the Michigan Parkinson Foundation, the premier statewide PD support organization, will enhance the unique recruitment base at MSU. Collaboration with the University of Michigan, as well as regional neurologists and movement disorders subspecialty providers, will foster efficient and comprehensive patient ascertainment. MSU neurologists with expertise in movement disorders will enroll and follow patients. MSU's previous experience with large, longitudinal clinical trials provide a proven track record in recruiting, retention and data acquisition in similar multi-center studies of neurological disease. MSU is an optimum environment highly successful participation in the Parkinson Disease Neuroprotection Clinical Trial. •
Project Title: NEUROPROTECTION IN PARKINSON DISEASE: CLINICAL CENTER Principal Investigator & Institution: Elble, Rodger; Interim Chairman & Medical Director; Neurology; Southern Illinois University Sch of Med P.O. Box 19616 Springfield, Il 627949616 Timing: Fiscal Year 2005; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): We propose that Southern Illinois University Parkinson Disease Center participate in the design and performance of a large, multicenter clinical trial of neuroprotective agents in Parkinson disease. There are more than 500,000 people in the United States who are affected by Parkinson disease with 50,000 new cases each year. The annual cost is estimated to be 10 billion dollars per year [1]. Parkinson disease is an age-related disease and with the aging of the baby boom population, the number of people with Parkinson disease will increase substantially after the year 2010. Parkinson disease is characterized by a long preclinical phase, the onset of symptoms at about 60 years of age and progression to severe disability over about 10 to 25 years. The objective of the present project is to identify compounds that are safe and effective in retarding clinical progression in Parkinson disease. The specific aims of the project are to: (1) identify compounds that have potential as neuroprotective agents in Parkinson disease; (2) design clinical trials to test the effects of experimental compounds on the rate of progression of Parkinson disease; (3) conduct pilot studies of selected compounds to determine tolerance and safety of their use in man; and, (4)
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Parkinson Disease
conduct a large, multicenter clinical trial to determine if selected compounds retard the rate of progression in Parkinson disease. The final design of the pilot studies and large, multicenter clinical trial will be developed collaboratively by the Steering and Oversight Committees, the Coordinating Center and Statistical Center, and the NINDS Scientific Program Director for the project. The following suggestions are proposed regarding the study design: (1) to include the study of estrogen as a potential neuroprotective agent in Parkinson disease; (2) to stratify the study population on the basis of rural vs. urban residence; (3) to use cognitive impairment as one of the measures of the progression of Parkinson disease; (5) to study the pharmacogenomics of the selected compounds studied in the large clinical trial; and, (6) to include a brain autopsy study to confirm the diagnosis and a neuropathology study of the effects of the selected compounds tested on the pathological changes in Parkinson disease. It is proposed that the Autopsy/Neuropathology Program at Southern Illinois University serve as the central resource for a brain autopsy and neuropathology study if it is included in the final study design. •
Project Title: PARKIN SYNAPTOTAGMIN
FUNCTION:
REGULATION
OF
MEMBERS
OF
Principal Investigator & Institution: Huynh, Duong Phuoc.; Cedars-Sinai Medical Center 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2005; Project Start 11-APR-2005; Project End 31-MAR-2010 Summary: (provided by applicant): Parkinson’s disease (PD) is a disabling movement disorders caused by reduced dopamine levels in the striatum resulting from the death of dopaminergic neurons in the substantia nigra. Inactivating mutations in the parkin gene cause autosomal recessive-juvenile Parkinson disease with dystonia (PARK2), but can also cause a later onset tremor-predominant disease indistinguishable from sporadic PD. Using the yeast two-hybrid system, we have identified new parkin binding proteins: members of the synaptotagmin (syt) family, and a novel protein with homologies to the beta-adrenergic receptor. We will test the following hypotheses: Parkin regulates the level of synaptotagmin 1 (syt1) and protects against cell death induced by syt1 overexpression, whereas mutated parkin proteins do not. As syt1 is a key protein involved in vesicle docking, fusion, and recycling, changes in cellular parkin levels by overexpression or knockdown will alter synaptic vesicle release and uptake. Parkin deficiency results in increased levels of intracellular free dopamine, thus increasing oxidative stress in dopaminergic neurons. To further elucidate the role of parkin in neuronal dysfunction and cell death, three specific aims are proposed: 1) We will investigate the role of syt1 in causing cell death, and the protective role of parkin using MTT and trypan blue exclusion assays. We will use Tet-Off PC12 cells expressing regulated levels of syt1 or parkin and mouse primary dopaminergic neurons. We will co-express parkin with syt1 to determine if parkin protects these cells from syt1-induced cytotoxicity. Lentiviral vectors will be used to achieve consistent expression levels. 2) We will investigate the role of parkin on presynaptic vesicle release and uptake by measuring the release and reuptake of styryl fluorescent FM4- 64 dyes in response to overexpression and knockdown of parkin and syt1. We will use established parkin siRNAs to block the synthesis of endogenous parkin, and then determine its effect on synaptic vesicle release and reuptake. 3) We will investigate the role of parkinsynaptotagmin interaction and parkin deficiency on vesicular and cytoplasmic levels of dopamine in PC12 cells and dopaminergic neurons. The ultimate goal of this proposal is to elucidate how parkin deficiency results in dopaminergic dysfunction and cell death in Parkinson’s disease.
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Project Title: PARKIN INTERACTING PROTEINS Principal Investigator & Institution: Pulst, Stefan M.; Warschaw Chair and Professor; Cedars-Sinai Medical Center 8700 Beverly Blvd Los Angeles, Ca 90048 Timing: Fiscal Year 2005; Project Start 15-SEP-2005; Project End 30-JUN-2007 Summary: (provided by applicant): Mutations in the parkin gene cause PARK2, a predominantly early-onset autosomal recessive form of Parkinsonism. Parkin mutations are also found in patients with tremor-predominant later onset forms of Parkinson disease (PD) indistinguishable from idiopathic Parkinson’s disease. Parkin is an E3 ubiquitin ligase that attaches ubiquitin chains to several proteins destined for degradation through the proteasome-dependent protein degradation pathway. Some proteins that interact with parkin, such as a-synuclein and synphilin-1, have themselves been found to cause Parkinson’s disease, when mutated. In previous experiments, we identified two members of the synaptotagmin (syt) family as parkin binders. We have now identified a novel parkin-binding protein with homologies to synapsin, designated synapsin-like-protein (SLP). SLP and synaptotagmin XI are both found in Lewy bodies of PD patients. We will test the following hypotheses: 1) parkin interacts and regulates a select group of synaptic vesicle associated proteins. 2) Genes encoding these proteins contain causative mutations or predisposing sequence variants in patients with familial or sporadic forms of Parkinsonism. Two Specific Aims are proposed: 1) We will further characterize the parkin-SLP interaction, and investigate whether mutant parkins lose the ability to bind SLP or to ubiquitinate SLP. We will determine whether parkin accelerates degradation of SLP. 2) We will explore sequence variants in the SLP, SYT1 and SYT11 genes in two PD patient groups and five matched control groups. We will establish which variants represent rare causative mutations and which variants may constitute susceptibility alleles. Variants will be tested for cell toxicity using an in vitro assay. The ultimate goal of this R21 proposal is to further characterize proteins involved in parkin function and to screen these proteins for mutations or susceptibility alleles in PD patients.
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Project Title: PARKINSON DISEASE COLLABORATIVE STUDY OF GENETIC LINKAGE Principal Investigator & Institution: Foroud, Tatiana M.; Professor; Medical and Molecular Genetics; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2005; Project Start 01-SEP-1998; Project End 31-JAN-2009 Summary: (provided by applicant): In 1998, in response to an NIH invitation (PA-96050) for investigator-initiated research on genetic factors that may be important in the development of Parkinson Disease (PD) a collaborative research effort to identify susceptibility genes for PD was established between Indiana University and investigators currently at the University of Rochester, the Parkinson Study Group (PSG), the University of California, San Diego, Cincinnati Children' s Hospital Medical Center, and the University of California, Irvine. During the first 4.5 years of this grant award, 422 multiplex PD families with 550 affected sibling pairs were recruited and rigorously evaluated. These genetically informative families were used to examine the role of the parkin gene in familial Parkinson’s disease. Additionally, a genome screen was completed and evidence of linkage to chromosomes 2, 10 and X was consistently found in these family-based samples. During the next 5 years, we propose to extend our current results to: 1) continue to ascertain multiplex families with PD and thereby increase our power to detect and isolate PD susceptibility genes; 2) further examine the role of the parkin gene in PD through careful clinical evaluation of families with known
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Parkinson Disease
parkin mutations; 3) identify the genes contributing to PD susceptibility in our multiplex families; and 4) test the role of any putative candidate genes identified through our family-based studies in a sample of sporadic PD cases and unaffected controls. In this way, we will expand the understanding of the etiology, pathogenesis, diagnosis, and ultimately, the prevention of this disease. To accomplish these goals we will focus on the following Specific Aims: 1. Expand the family resources so as to increase the power to identify the genes contributing to PD susceptibility. 2. Study the role of parkin mutations in Parkinson’s disease. 3. Perform molecular studies to identify PD susceptibility genes. 4. Evaluate putative PD susceptibility genes in a case-control sample. •
Project Title: PARKINSON DISEASE NEUROPROTECTION CLINICAL TRIAL CENTER Principal Investigator & Institution: Manyam, Bala V.; Professor (Emeritus) and Director (Retir; Scott and White Memorial Hospital 2401 S 31St St Temple, Tx 76504 Timing: Fiscal Year 2005; Project Start 30-SEP-2002; Project End 01-SEP-2005 Summary: (provided by applicant): This application is in response to the Parkinson agenda for the NIH for the initiation of a randomized controlled clinical trial to test potential neuroprotectants in patients with early Parkinson’s disease. The neuroprotectants to be tested in the trial have not yet been chosen and will be selected by an NINDS-appointed oversight committee. It is expected that NIH will fund 42 Parkinson's Disease Neuroprotection Clinical Centers to the institutions who demonstrate the ability to recruit subjects and provide high quality data for the trial(s). This application describes the characteristics of the staff and Parkinson’s disease clinical center at Scott & White Clinic/Texas A & M College of Medicine that will be able to fulfill these goals. The following specific aims will be met subject to final common protocol finalized by the NINDS-appointed oversight committee. 1). Recruit 12 or more patients in the early stages of Parkinson’s disease for the pilot study. 2). Recruit 72 or more patients for the main study once the final neuroprotectant is chosen from the initial pilot studies. The above patients will be in the early, mild Parkinson’s disease, not yet requiring symptomatic treatment and unexposed to prior treatment with levodopa/dopamine agonist/selegiline (within four months). 3). For primary outcome measure to assess the degree of Parkinson’s disease, and its progression the Unified Parkinson's Disease Rating Scale (UPDRS) (or one selected by NINDS-appointed oversight committee) will be followed for a highly reliable functional outcome or disability scale that is multi-modal in each subject and other protocols that may be implemented with the subject and investigator remaining "blinded" as to treatment assignment through the duration of the study. 4). For secondary outcome measures, monitor any adverse events from medication(s), quality of life measurement, depression, dementia and others by use of appropriate scales included in the final common protocol (such as Adverse Reaction Form, Hamilton Depression Scale and Mini-Mental State Exam) over the duration of the study. The PI has a proven track record in having participated in a large number of clinical trials involving early Parkinson’s disease patients, has been involved in drug development for Parkinson’s disease and has a team of well qualified staff, with access to large number of early Parkinson’s disease patients including women and minority patients, through a network of a large primary care physicians along with a long-term track record of involvement in both laboratory and clinical care in the treatment of Parkinson’s disease. Thus, the investigators have adequate experience, resources, and proven ability to recruit suitable early Parkinson’s disease subjects and carry out the clinical trial to meet the requirements of RFA-NS-02-010 in a timely manner.
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Project Title: PARKINSON DISEASE NEUROPROTECTION TRIAL: CLINICAL CENTER Principal Investigator & Institution: Martin, W W.; University of Alberta Research Services Office Edmonton, Ab T6g 2E1 Timing: Fiscal Year 2006; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): The long-term objectives are to develop a neuroprotective strategy that can be applied to patients with Parkinson’s disease (PD) in order to alter disease progression, and to evaluate in the setting of a multi-center clinical trial the efficacy of any such strategies. In PD, there is a prolonged course of progressive neuronal loss which is not altered by existing treatments. The development of neuroprotective strategies is therefore important to lessen the medical, societal, and economic impact of PD-related disability Patients will be recruited with early Parkinson’s disease who have been symptomatic for fewer than five years, and who have received levodopa or dopamine agonists for no more than six months. Patients will be followed clinically over a period of three years to assess the potential neuroprotective benefit associated with a drug or drugs chosen by the Steering Committee. Although the multi-center trial will be based on clinical rather than surrogate endpoints, at this site, magnetic resonance imaging will be used to obtain a quantitative index of regional brain iron concentration which we hypothesize to correlate with disease progression.
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Project Title: PARKINSON'S DIS. NEUROPROTECTION:BROOKLYN CLINICAL CTR. Principal Investigator & Institution: Bodis-Wollner, Ivan G.; Professor of Ophthalmology; Neurology; Suny Downstate Medical Center 450 Clarkson Ave Brooklyn, Ny 11203 Timing: Fiscal Year 2005; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): This is an application to be selected to become one of the centers of an NIH directed research to Brooklyn explore therapeutic agents in the prevention and retardation of neural degeneration in Parkinson’s disease. The location and patient population of our Parkinson's Disease and Related Disorders Center is unique. We serve a large population of minority Parkinson Disease patients consisting almost entirely of black Afro-Americans and of Caribbean descent in the heaviest populated borough, Brooklyn, New York. We have more than the requested minimum new patients for the study even though the bulk of our patients are not specifically referred but diagnosed in our general neurology clinic. We will implement visiting nurse service to ensure retention.What we will contribute by participation in the neuroprotective study are to:provide scientifically usable data from OUR neurodegenerative study in the minority population enhance the capability of the federal health system to embrace this minority population with forefront treatment possibilities provide the best available care to a large segment of the Brooklyn minority population.
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Project Title: PARKINSON'S DISEASE CLINICAL TRIAL GROUP SITE Principal Investigator & Institution: Taylor, John R.; Mcguire Research Institute, Inc. 1201 Broad Rock Blvd, Res 151 Richmond, Va 23249 Timing: Fiscal Year 2005; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Researchers at the McGuire Veterans Affairs Medical Center (MVAMC) bring to the Parkinson Disease (PD) Neuroprotection Clinical Trial Group exceptional expertise, outstanding clinical and laboratory resources,
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Parkinson Disease
and a qualified and motivated patient population from which to recruit subjects. The McGuire Parkinson Disease Research, Education, and Clinical Center (PADRECC) provides PD treatment for military personnel and veterans throughout the southeastern United States, ranging from Pennsylvania down to Florida (including Puerto Rico) and west to the Mississippi River. Veterans with PD from this entire region are referred to MVAMC for treatment. Native Americans in this region seeking treatment for PD and patients referred from private practice are also eligible to attend the MVAMC PADRECC. This combined pool of potential study participants will exceed the enrollment needs for a member site of the proposed PD Neuroprotection Clinical Trial Group. The research mission of the MVAMC PADRECC is to establish a center of excellence for clinical trials, emerging biomolecular strategies, and integrated health services. The MVAMC and its affiliate university, Virginia Commonwealth University/Medical College of Virginia Hospitals (VCU/MCVH), boast a talented group of scientist-practitioners with a broad range of clinical interests and research expertise related to PD. The MVAMC PADRECC personnel, resourc6s, and patient population will be available for the PD Neuroprotection Clinical Trial Group. MVAMC investigators have a long history of excellent recruitment and retention capabilities and a supportive clinical environment in which to conduct studies. Their history of participation in multicenter trials managed by pharmaceutical companies, the Parkinson Study Group, and the NIH demonstrate their commitment to cooperative research projects. MVAMC investigators will cooperate fully with all other centers in the PD Neuroprotection Clinical Trial Group in the conduct of each pilot and main study to test agents approved by the Oversight and Steering Committees. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PARKINSON'S DISEASE NEUROPROTECTION TRIAL Principal Investigator & Institution: Burns, Richard; St. Joseph's Hospital and Medical Center 350 West Thomas Road Phoenix, Az 85013 Timing: Fiscal Year 2006; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): The objective of this application is to be selected by the Neurodegeneration and Clinical Trial Groups of the NINDS to participate in the Parkinson Disease Neuroprotection Clinical Trial. It is our understanding that the study design will include 42 clinical sites, the use of two or more neuroprotective agents, and an initial pilot study followed by a larger trial of approximately 3000 subjects with early Parkinson's Disease. It is also our understanding that the protocol for this study is currently under development by representatives from the coordinating center, statistical center, the NINDS Oversight Committee and others. As a clinical site for the study, Dr. Mark Stacy and the research staff at the Muhammad Ali Parkinson Research Center (MAPRC) at Barrow Neurological Institute agree to recruit and follow the required number of participants for the duration of the study, collect accurate and timely data and strictly adhere to the protocol.As a major referral center for Parkinson's Disease patients in the southwestern United States, approximately 4800 PD patients are examined and treated annually at our site. The MAPRC has extensive experience in the execution of clinical trials in the Parkinson's population, averaging approximately 15 to 20 clinical research studies annually. If given the opportunity to act as a clinical center for the Parkinson Disease Neuroprotection trial we will recruit the appropriate number of eligible subjects, taking special effort to ensure adequate representation of females and minorities. We will take all appropriate measures to protect these subjects and follow the participants for the entire duration of the trial.
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Project Title: PARKINSON'S NEUROPROTECTION TRIAL: CLINICAL CENTER IN SHREVEPORT Principal Investigator & Institution: Zweig, Richard M.; Neurology; Louisiana State Univ Hsc Shreveport 1501 Kings Hwy Shreveport, La 711303932 Timing: Fiscal Year 2006; Project Start 02-JUN-2006; Project End 30-NOV-2010 Summary: (provided by applicant): This application is in response to RFA-NS-05-004 entitled "Parkinson Disease Neuroprotection Clinical Trial: Clinical Centers." The specific aim is to collaborate, as a clinical center, in clinical trials to test potential neuroprotective agents in patients with Parkinson’s disease. This is a timely and exciting initiative as, despite the availability of increasingly sophisticated medical and surgical treatments to alleviate many of its symptoms, no treatment has, to date, been definitively proven to slow or arrest the progression of Parkinson’s disease. As director of the Movement Disorders Section of the Department of Neurology at LSU Health Sciences Center - Shreveport, serving as a medical hub for a region that includes northern and central LA, northeast TX, and southwestern AR with well over 500,000 people, the PI actively follows 333 patients with a diagnosis of Parkinson’s disease in private office, hospital-based, and VA clinics. He has established local and regional support groups, comprehensive rehabilitation programs, and a privately funded resource center for patients that also serve as a source of pilot funding for Parkinson'srelated research. As investigator and coordinator members of the Parkinson Study Group (PSG), the PI and this study's designated nurse coordinator are currently participating in a PSG sponsored trial of a medication for early, untreated, Parkinson’s disease. Eleven patients were randomized for this study in under 16 months; all of these patients have remained in this study (last patient enrolled 1/04), with strict protocol adherence maintained. The PI is currently participating in an additional double-blind study for more advanced patients, and in an open-label study of the same medication. In previous trials with this and other medications, enrollment goals were typically achieved. The PI should have no difficulty in recruiting one or more de novo participants per month for pilot trials, and up to 2 or more per month during the phase 3 trial that will include patients recently started on symptomatic therapy. Support for this study has been offered by the Department, by neurologists in the community and local VA, by the Parkinson Association of LA, and by regional support groups. An afternoon clinic will be set aside for evaluating newly referred patients, including minorities and women, who might be candidates for this study. A secretary dedicated full-time to Parkinson's activities will assist with recruitment and a student worker will assist with data management.
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Project Title: PD NEUROPROTECTION CLINICAL TRIAL: CLINICAL CENTERS Principal Investigator & Institution: Hauser, Robert A.; Neurology; University of South Florida 3650 Spectrum Blvd., Suite 160 Tampa, Fl 33612 Timing: Fiscal Year 2005; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Specific Aim 1: To participate as a clinical center in the National Institute of Neurological Disorders and Stroke (NINDS) Parkinson Disease Neuroprotection clinical trial.The University of South Florida Parkinson's Disease and Movement Disorders Center and affiliated clinics will enroll at least 84 subjects with early Parkinson’s disease over 3 1/2 years as part of the NINDS simple neuroprotection trial. The clinical trial will be conducted at the University of South Florida's Parkinson’s disease and Movement Disorders Center, a very active clinical care and clinical research facility located in Harbourside Medical Tower adjacent to Tampa General Hospital. Subjects will be recruited from this center and affiliated clinics. These include 1) James
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A. Haley VA Parkinson’s disease and Movement Disorders Center, 2) The University of South Florida Medical clinics and 3) The University of South Florida/Tampa General Hospital Indigent Care Neurology Clinic. The center has a proven track record and reputation as a high quality and high enrollment clinical trials site in Parkinson’s disease and other movement disorders. Over 54 clinical trials have been conducted at the center since its inception and 43 over the last 5 years. Over the last 5 years, 256 Parkinson’s disease patients have been entered in these clinical trials and 104 Parkinson’s disease patients with early Parkinson’s disease have been entered in the clinical trials.Participating physicians will include Robert A. Hauser, M.D., Thresa A. Zesiewicz, M.D., and Juan Sanchez-Ramos, M.D. Lisa Gauger will serve as administrator and Roberta Henneman will serve as study coordinator.Specific Aim II: To participate in the development of the design of the neuroprotection trial.Specific Aim III: To participate in the selection of possible neuroprotective agents to be studied. •
Project Title: PHYSICAL LIMITS OF QUANTITATIVE SPECT Principal Investigator & Institution: Kijewski, Marie Foley.; Assistant Professor; Brigham and Women's Hospital Research Administration Boston, Ma 02115 Timing: Fiscal Year 2005; Project Start 01-AUG-1993; Project End 31-MAR-2007 Summary: The long-term goal of this project is to develop quantitative imaging task based metrics and, using them, determine the fundamental limits on quantitative SPECT. In the previous project period, we focused on optimization of methods to correct for scatter, attenuation, and distance- dependent spatial resolution, as well as optimizing the acquisition strategy for imaging deep brain structures. In this renewal application, we turn our attention to the areas of simultaneous dual-isotope imaging, comparison of analytical and iterative image processing and reconstruction and on generalizing collimation advances, developed during the last project period for a dedicated brain system, to more commonly available dual-head systems. Our approaches include analysis, simulation, phantom experiments and patient studies. The analyses and simulation studies, although pertaining to prototypical estimation and classification tasks, will incorporate realistic anatomy and biological variability. We will continue the development of special-purpose collimators which sample the projections unequally in order to compensate for loss of information from central brain structures by attenuation. We will manufacture one such collimator, designed for a dedicated brain SPECT system during the last project period. We will design a similar collimator for a dual-head SPECT system, optimizing its performance for quantitative brain imaging tasks, relevant to Parkinson disease, using computer simulations of an anatomically realistic digital phantom. We will also determine the theoretical limits on activity estimation in simultaneous dual-energy imaging for both Tc/I and Tc/TI, and assess the value of dual-isotope imaging in clinical tasks related to glioblastoma and adult attention deficit hyperactivity disorder. We will compare analytical methods to correct for attenuation and distance dependent resolution to corrections incorporated into an iterative reconstruction algorithm in prototypical estimation tasks, as well as clinical tasks relevant to Alzheimer disease.
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Project Title: SOMATIC CELL GENE TRANSFER/NEUROLOGICAL & CLIN APPLICS Principal Investigator & Institution: During, Matthew J.; Professor and Director; Neurological Surgery; Weill Medical College of Cornell Univ 1300 York Avenue New York, Ny 10021 Timing: Fiscal Year 2005; Project Start 25-SEP-2004; Project End 31-MAY-2009
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Summary: (provided by applicant): Gene transfer in the mammalian nervous system has been the primary research focus of our laboratory for the past decade. We are excited that this RFA has come at a time when the field is flourishing, yet clinical translation remains daunting, and much work needs to be done for ultimate success in the clinic. In this grant application we propose to focus on some of the more pressing needs using rat models of Parkinson Disease. Our first aim is to further develop more efficient and readily packaged and purified AAV vectors for clinical translation. Here, we will characterize and compare pseudotyped and chimeric AAV vectors and in addition develop novel reagents, including helper plasmids and protocols which can be used by the entire gene therapy community to more efficiently generate these vectors. Our preliminary data suggests that these new chimeric and pseudotyped vectors represent a significant advance above our current generation rAAV-2 vectors. Secondly, we will develop optimal expression cassettes with a focus on promoter; post regulatory sequences as well as elements like the human beta-interferon scaffold attachment region (SAR) to boost expression. Thirdly, we will further develop a regulatable system. We present in our preliminary data our latest generation bi-directional tet cassette with tandem minimal insulator sequences flanking the vector genome. Here we propose to use this vector as the starting point to develop a novel cassette with the use of KRAB-AB domain from kid-1 as a suppressor. Our fourth aim is the use of rAAV to over express PAEL receptor in the adult rat substantial nigra with characterization of the phenotype as a potential genetic model of Parkinson Disease. Finally, we propose the use of a picospritzer and in vivo single unit recording to develop methods for focal and electrophysiological mapped neuronal gene delivery. We will target the substantia nigra pars compacta, using AAV expressing wildtype parkin, as a potential therapy for parkin mutation associated, autosomal recessive Parkinson Disease (AR-PD) as modeled by the PAEL receptor over expressing rats as developed in specific aim 4. •
Project Title: SOUTHEASTERN MICHIGAN PARKINSON'S DISEASE PROGRAM Principal Investigator & Institution: Lewitt, Peter A.; Professor of Neurology; William Beaumont Hospital Research Inst 3811 West 13 Mile Road, Suite 501 Royal Oak, Mi 48073 Timing: Fiscal Year 2006; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): This application responds to RFA-NS-02-010 ("Parkinson Disease Neuroprotection Trial: Clinical Centers"). The Southeastern Michigan Parkinson's Disease Program describes the research experience, facilities, and operational capabilities for collaborative sites that will work together closely: the William Beaumont Hospital System, the Clinical Neuroscience Center (CNC), a Parkinson’s disease (PD) research and treatment program in Southfield, and the PD clinics at the Wayne State University School of Medicine (WSU SOM) campus in Detroit. We propose to participate in a nationwide effort for recruiting and conducting randomized, double blind clinical trials of neuroprotection for PD. The CNC, designated by the National Parkinson Foundation as Michigan's Center of Excellence, has developed the State's largest PD patient base and referral network. For almost 20 years, the CNC has been one of the nation's leading sites for conducting Phase 1 through IV clinical research in PD. The CNC's extensive affiliations with the region's PD patient community as well as with health providers in Michigan, Ohio, and southwestern Ontario should maximize opportunities for recruiting de novo PD patients. The two sites will enhance the diversity of study participants, especially with the WSU SOM services to a large inner city population and a major Veterans Administration Medical Center.The CNC's extensive experience in PD drug research has involved clinical trials (including several neuroprotection studies) sponsored by the pharmaceutical industry,
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the NIH, and the Parkinson Study Group. The Principal Investigator is enthusiastic to participate in the multi-site collaborative program and can offer a leadership role in the choice and coordination of studies.This application also discusses concepts for three pharmacological agents that could be investigated in pilot studies and, if promising, in multicenter clinical trials for assessing neuroprotection. •
Project Title: SPEECH THERAPY FOR INDIVIDUALS WITH PARKINSON DISEASE Principal Investigator & Institution: Cole, Ronald A.; Mentor Machines, Inc. 4789 Sunshine Canyon Boulder, Co 80302 Timing: Fiscal Year 2005; Project Start 01-SEP-2005; Project End 30-APR-2006 Summary: (provided by applicant): PROJECT SUMMARY: We propose to develop and test the technical and clinical feasibility of computer-based system that conducts speech therapy with individuals with Parkinson disease. The system uses a virtual therapist-a lifelike animated three dimensional character that is programmed to emulate the behaviors of an expert speech clinician conducting LSVT (Lee Silverman Voice Therapy), an efficacious treatment that improves the speech communication abilities of individuals with Parkinson disease. LSVT is an intensive therapy, requiring sixteen one hour face-to-face sessions over a one month period by a trained clinician, resulting in a maximum case load of six to eight patients per clinician each month. The proposed system is expected to produce the same benefits as face-to-face therapy by enabling patients to work with the virtual therapist independently following an initial orientation and training session. To assure efficacious treatment, the system is designed to enable clinicians to monitor and review sessions and provide feedback to patients. The specific aims of the proposed work are to develop the proposed system and to demonstrate its technical and clinical feasibility in trials using LSVT clinicians and former LSVT patients. Successful outcomes of the proposed work will demonstrate the feasibility of developing a commercial product that will increase accessibility of LSVT therapy by a factor of 5 to 6, and reduce treatment costs significantly. RELEVANCE: Although 90% of the over 1.5 million individuals with Parkinson disease suffer from speech and voice disorders that significantly impact their quality of life, only 3% to 4% of these individuals receive speech therapy. The proposed work will benefit the health and well being these individuals by providing accessible and effective treatment to improve their speech communication abilities. The research will also contribute to scientific knowledge by demonstrating that virtual therapy offers the potential to provide inexpensive and accessible behavioral therapy for individuals with various neurological disorders.
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Project Title: THE ROLES OF A-SYNUCLEIN AND PARKIN IN PARKINSON DISEASE Principal Investigator & Institution: Schlossmacher, Michael G.; Brigham and Women's Hospital Research Administration Boston, Ma 02115 Timing: Fiscal Year 2005; Project Start 30-SEP-1999; Project End 28-FEB-2006 Summary: (provided by applicant): The pathogenesis of Parkinson disease (PD) is unknown but dopamine-induced oxidative stress, proteasomal abnormalities and mitochondrial dysfunction are associated with its neurodegeneration. Rare heritable forms of PD are linked to an increasing number of gene loci. At the PARK1 locus, SNCA encodes a neuronal protein, alpha-synuclein (alpha-S), that is involved in the transition of synaptic vesicles from the reserve-resting pool to the readily releasable pool in vivo and in vitro. It is linked to sporadic PD by the formation of fibrillar inclusions that
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contain phosphorylated alpha-S, and to autosomal dominant PD by a likely gain-offunction effect of two infrequent point mutations. The PARK2 gene encodes parkin, an E3 ubiquitin ligase. It is mutated in <50% of all autosomal recessive PD cases by a probable loss-of-function phenomenon. In normal human brain (but not rat brain), a pool of alpha-S undergoes O-linked glycosylation, thereby generating alpha-Sp22. This glycoprotein is a substrate for parkin's E3 ligase function in vitro and accumulates in PARK2-mutant PD brain. The central hypotheses of this application state that 1) a shared pathogenetic pathway is encoded by PD-linked genes, 2) characterization of the alpha-S glycosylation in primate brain will provide insights into the pathogenesis of PD, 3) the normal function of the Parkin E3 complex is essential for the sustained survival of catecholaminergic neurons in adult human brain, and 4) the identification of the in vivo subunits of the assembled parkin E3 complex will validate reported binding partners and reveal potentially neurotoxic substrates. To this end, I have identified two Specific Aims: Aim 1: To characterize the glycosylation of alpha-S in human control brain as well as PARK1-linked PD brain and to model its biosynthesis in a cell model, and Aim 2: To biochemically purify the subunits of the Parkin E3 ligase complex from human brain, and verify them in vitro. •
Project Title: UAB PD NEUROPROTECTION CLINICAL TRIAL CENT* Principal Investigator & Institution: Watts, Ray L.; Professor and Vice Chairman of Neurology; Neurology; University of Alabama at Birmingham 1530 3Rd Avenue South Birmingham, Al 35294 Timing: Fiscal Year 2005; Project Start 30-SEP-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Emory University has all of the necessary components to become a Parkinson's Disease Neuroprotection Clinical Trial Center. There are an estimated 50,000 persons currently diagnosed with Parkinson’s disease and an estimated 5,000 newly diagnosed patients each year in the area served by Emory University. The demographic characteristics of the area served by Emory University allows for the recruitment of an ethnically diverse population of study patients. Emory University is an established Clinical Trials Center with the necessary space to efficiently conduct clinical trials, prepare and process lab specimens and securely and confidentially maintain study medication and documentation. An experienced clinical trial team is currently in place to assure that the studies are conducted in a manner which allows for accurate, efficient and timely collection of data and provides a safe and pleasant environment for the patients. The Clinical Trial Staff have all received training and certification to conduct clinical trials from the Emory University Institutional Review Board and have been trained and currently follow Good Clinical Practice Guidelines to assure the safety and protection of study participants. The Principal Investigator, Dr. Ray L. Wafts, has extensive experience in developing, conducting and monitoring clinical trials and an excellent track record in the recruitment of patients. The Center currently works closely with the American Parkinson Disease Association and all of its local chapters and support groups to facilitate patient recruitment through multiple resources provided to the Center by the American Parkinson Disease Association. Emory University's Advanced Center for Parkinson Research/A. Worley Brown Family PD Clinical Research Unit is willing and dedicated to adhering to a common protocol and to cooperate with other centers and NINDS in the conduct of both pilot studies and the main efficacy study.
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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.13 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 Parkinson disease, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type Parkinson disease (or synonyms) into the search box, and click Go. The following is the type of output you can expect from PubMed for Parkinson disease (hyperlinks lead to article summaries): •
A case-control association study of the 12 single-nucleotide polymorphisms implicated in Parkinson disease by a recent genome scan. Author(s): Li Y, Rowland C, Schrodi S, Laird W, Tacey K, Ross D, Leong D, Catanese J, Sninsky J, Grupe A. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16685663&query_hl=40&itool=pubmed_docsum
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A common genetic factor for Parkinson disease in ethnic Chinese population in Taiwan. Author(s): Fung HC, Chen CM, Hardy J, Singleton AB, Wu YR. Source: Bmc Neurology [electronic Resource]. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17187665&query_hl=40&itool=pubmed_docsum
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A controlled trial of rasagiline in early Parkinson disease: the TEMPO Study. Author(s): Parkinson Study Group. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12470183&query_hl=40&itool=pubmed_docsum
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A precipitating role for truncated alpha-synuclein and the proteasome in alphasynuclein aggregation: implications for pathogenesis of Parkinson disease. Author(s): Liu CW, Giasson BI, Lewis KA, Lee VM, Demartino GN, Thomas PJ. Source: The Journal of Biological Chemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15840579&query_hl=40&itool=pubmed_docsum
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PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease. Author(s): The NINDS NET-PD Investigators. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17200487&query_hl=40&itool=pubmed_docsum
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A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations. Author(s): Blindauer K, Shoulson I, Oakes D, Kieburtz K, Schwid S, Fahn S, Stern M, Goetz C, Nutt J, Goren S, Sayag N, Scolnik M, Levy R, Eyal E, Salzman P, Pagano M; Parkinson Study Group. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16476809&query_hl=40&itool=pubmed_docsum
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A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Author(s): NINDS NET-PD Investigators. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16481597&query_hl=40&itool=pubmed_docsum
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Acoustic analysis of clear versus conversational speech in individuals with Parkinson disease. Author(s): Goberman AM, Elmer LW. Source: Journal of Communication Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15748725&query_hl=40&itool=pubmed_docsum
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Acute akinesia in Parkinson disease. Author(s): Onofrj M, Thomas A. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15824341&query_hl=40&itool=pubmed_docsum
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Acute cervical motor radiculopathy induced by neck and limb immobilization in a patient with Parkinson disease. Author(s): Shimizu T, Komori T, Hayashi H. Source: Intern Med. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16847370&query_hl=40&itool=pubmed_docsum
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Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA). Author(s): Jellinger KA. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15977648&query_hl=40&itool=pubmed_docsum
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Alpha-synuclein lesions in normal aging, Parkinson disease, and Alzheimer disease: evidence from the Baltimore Longitudinal Study of Aging (BLSA). Author(s): Mikolaenko I, Pletnikova O, Kawas CH, O'Brien R, Resnick SM, Crain B, Troncoso JC. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15751230&query_hl=40&itool=pubmed_docsum
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An algorithmic approach to understand trace elemental homeostasis in serum samples of Parkinson disease. Author(s): Pande MB, Nagabhushan P, Hegde ML, Rao TS, Rao KS. Source: Computers in Biology and Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15780860&query_hl=40&itool=pubmed_docsum
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Apathy does not equal depression in Parkinson disease: why we should care. Author(s): Richard IH. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16832069&query_hl=40&itool=pubmed_docsum
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Apomorphine: a rapid rescue agent for the management of motor fluctuations in advanced Parkinson disease. Author(s): Kolls BJ, Stacy M. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16960475&query_hl=40&itool=pubmed_docsum
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Approach to diagnosis of Parkinson disease. Author(s): Frank C, Pari G, Rossiter JP. Source: Can Fam Physician. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16893149&query_hl=40&itool=pubmed_docsum
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Association between family history of dementia and hallucinations in Parkinson disease. Author(s): Paleacu D, Schechtman E, Inzelberg R. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15911796&query_hl=40&itool=pubmed_docsum
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Association between the neuron-specific RNA-binding protein ELAVL4 and Parkinson disease. Author(s): Noureddine MA, Qin XJ, Oliveira SA, Skelly TJ, van der Walt J, Hauser MA, Pericak-Vance MA, Vance JM, Li YJ. Source: Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15827745&query_hl=40&itool=pubmed_docsum
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Association of dopamine agonist use with impulse control disorders in Parkinson disease. Author(s): Weintraub D, Siderowf AD, Potenza MN, Goveas J, Morales KH, Duda JE, Moberg PJ, Stern MB. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16831966&query_hl=40&itool=pubmed_docsum
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Atypical antipsychotics in the elderly with Parkinson disease and the "black box" warning. Author(s): Friedman JH. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16924004&query_hl=40&itool=pubmed_docsum
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Behavioural changes after bilateral subthalamic stimulation in advanced Parkinson disease: a systematic review. Author(s): Temel Y, Kessels A, Tan S, Topdag A, Boon P, Visser-Vandewalle V. Source: Parkinsonism & Related Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16621661&query_hl=40&itool=pubmed_docsum
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Beneficial effects of testosterone replacement for the nonmotor symptoms of Parkinson disease. Author(s): Okun MS, Walter BL, McDonald WM, Tenover JL, Green J, Juncos JL, DeLong MR. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12433262&query_hl=40&itool=pubmed_docsum
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Benefits of rivastigmine on attention in dementia associated with Parkinson disease. Author(s): Wesnes KA, McKeith I, Edgar C, Emre M, Lane R. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16301500&query_hl=40&itool=pubmed_docsum
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Biceps pain as the presenting symptom of Parkinson disease: effective treatment with L-dopa. Author(s): Gilbert GJ. Source: Southern Medical Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15352675&query_hl=40&itool=pubmed_docsum
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Bilateral high-frequency stimulation in the subthalamic nucleus for the treatment of Parkinson disease: correlation of therapeutic effect with anatomical electrode position. Author(s): Voges J, Volkmann J, Allert N, Lehrke R, Koulousakis A, Freund HJ, Sturm V. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11838801&query_hl=40&itool=pubmed_docsum
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Bilateral stimulation of the subthalamic nucleus in patients with Parkinson disease: a study of efficacy and safety. Author(s): Simuni T, Jaggi JL, Mulholland H, Hurtig HI, Colcher A, Siderowf AD, Ravina B, Skolnick BE, Goldstein R, Stern MB, Baltuch GH. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11990805&query_hl=40&itool=pubmed_docsum
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Bilateral subthalamic stimulation in patients with Parkinson disease: long-term follow up. Author(s): Pahwa R, Wilkinson SB, Overman J, Lyons KE. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12854747&query_hl=40&itool=pubmed_docsum
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Bilineal transmission of Parkinson disease on Crete suggests a complex inheritance. Author(s): Spanaki C, Plaitakis A. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15007141&query_hl=40&itool=pubmed_docsum
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Body mass index and the risk of Parkinson disease. Author(s): Hu G, Jousilahti P, Nissinen A, Antikainen R, Kivipelto M, Tuomilehto J. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17159100&query_hl=40&itool=pubmed_docsum
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Bornaprine vs placebo in Parkinson disease: double-blind controlled cross-over trial in 30 patients. Author(s): Cantello R, Riccio A, Gilli M, Delsedime M, Scarzella L, Aguggia M, Bergamasco B. Source: Italian Journal of Neurological Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3514543&query_hl=40&itool=pubmed_docsum
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Botulinum toxin injections do not improve freezing of gait in Parkinson disease. Author(s): Wieler M, Camicioli R, Jones CA, Martin WR. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16116132&query_hl=40&itool=pubmed_docsum
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Brain imaging to assess the effects of dopamine agonists on progression of Parkinson disease. Author(s): Morrish PK. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12117387&query_hl=40&itool=pubmed_docsum
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Brain imaging to assess the effects of dopamine agonists on progression of Parkinson disease. Author(s): Albin RL, Nichols TE, Frey KA. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12117386&query_hl=40&itool=pubmed_docsum
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Brain imaging to assess the effects of dopamine agonists on progression of Parkinson disease. Author(s): Ahlskog JE, Maraganore DM, Uitti RJ, Uhl GR. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12117385&query_hl=40&itool=pubmed_docsum
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Brain iron in patients with Parkinson disease: MR visualization using gradient modification. Author(s): Norfray JF, Chiaradonna NL, Heiser WJ, Song SH, Manyam BV, Devleschoward AB, Eastwood LM. Source: Ajnr. American Journal of Neuroradiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3128074&query_hl=40&itool=pubmed_docsum
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Brain magnetic resonance imaging in multiple-system atrophy and Parkinson disease: a diagnostic algorithm. Author(s): Bhattacharya K, Saadia D, Eisenkraft B, Yahr M, Olanow W, Drayer B, Kaufmann H. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12020268&query_hl=40&itool=pubmed_docsum
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Brain peroxidase and catalase in Parkinson disease. Author(s): Ambani LM, Van Woert MH, Murphy S. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=1122174&query_hl=40&itool=pubmed_docsum
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Brain transplantation of human neural stem cells transduced with tyrosine hydroxylase and GTP cyclohydrolase 1 provides functional improvement in animal models of Parkinson disease. Author(s): Kim SU, Park IH, Kim TH, Kim KS, Choi HB, Hong SH, Bang JH, Lee MA, Joo IS, Lee CS, Kim YS. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16708545&query_hl=40&itool=pubmed_docsum
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Bromocriptine in Parkinson disease. Author(s): Lieberman AN, Goldstein M. Source: Pharmacological Reviews. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3901046&query_hl=40&itool=pubmed_docsum
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Budipine provides additional benefit in patients with Parkinson disease receiving a stable optimum dopaminergic drug regimen. Author(s): Przuntek H, Bittkau S, Bliesath H, Buttner U, Fuchs G, Glass J, Haller H, Klockgether T, Kraus P, Lachenmayer L, Muller D, Muller T, Rathay B, Sgonina J, Steinijans V, Teshmar E, Ulm G, Volc D. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12020263&query_hl=40&itool=pubmed_docsum
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Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Author(s): McSherry JW. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15781848&query_hl=40&itool=pubmed_docsum
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Cardiovascular aspects of Parkinson disease. Author(s): Goldstein DS. Source: Journal of Neural Transmission. Supplementum. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17017550&query_hl=40&itool=pubmed_docsum
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Cardiovascular response to treadmill testing in Parkinson disease. Author(s): Werner WG, DiFrancisco-Donoghue J, Lamberg EM. Source: J Neurol Phys Ther. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16796771&query_hl=40&itool=pubmed_docsum
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Challenging the serotonergic system in Parkinson disease patients: effects on cognition, mood, and motor performance. Author(s): Scholtissen B, Verhey FR, Adam JJ, Weber W, Leentjens AF. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16960473&query_hl=40&itool=pubmed_docsum
Studies
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Classification of locomotor activity by acceleration measurement: validation in Parkinson disease. Author(s): Keenan DB, Wilhelm FH. Source: Biomed Sci Instrum. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15850127&query_hl=40&itool=pubmed_docsum
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Clinical correlates of levodopa-induced dopamine release in Parkinson disease: a PET study. Author(s): Pavese N, Evans AH, Tai YF, Hotton G, Brooks DJ, Lees AJ, Piccini P. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17101892&query_hl=40&itool=pubmed_docsum
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Clinical features and gene analysis in Korean patients with early-onset Parkinson disease. Author(s): Chung EJ, Ki CS, Lee WY, Kim IS, Kim JY. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16908747&query_hl=40&itool=pubmed_docsum
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Clinical features associated with impulse control disorders in Parkinson disease. Author(s): Pontone G, Williams JR, Bassett SS, Marsh L. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17030761&query_hl=40&itool=pubmed_docsum
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Clinical features of Parkinson disease patients with homozygous leucine-rich repeat kinase 2 G2019S mutations. Author(s): Ishihara L, Warren L, Gibson R, Amouri R, Lesage S, Durr A, Tazir M, Wszolek ZK, Uitti RJ, Nichols WC, Griffith A, Hattori N, Leppert D, Watts R, Zabetian CP, Foroud TM, Farrer MJ, Brice A, Middleton L, Hentati F. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16966502&query_hl=40&itool=pubmed_docsum
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Clinical pharmacology of rasagiline: a novel, second-generation propargylamine for the treatment of Parkinson disease. Author(s): Chen JJ, Swope DM. Source: Journal of Clinical Pharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16027398&query_hl=40&itool=pubmed_docsum
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Clinical phenotype of Parkinson disease dementia. Author(s): Galvin JE, Pollack J, Morris JC. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17101891&query_hl=40&itool=pubmed_docsum
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Cognitive changes following subthalamic nucleus stimulation in two patients with Parkinson disease. Author(s): Moretti R, Torre P, Antonello RM, Capus L, Gioulis M, Marsala SZ, Cazzato G, Bava A. Source: Percept Mot Skills. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12434839&query_hl=40&itool=pubmed_docsum
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Cognitive status correlates with neuropathologic stage in Parkinson disease. Author(s): Braak H, Rub U, Jansen Steur EN, Del Tredici K, de Vos RA. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15851731&query_hl=40&itool=pubmed_docsum
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Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease. Author(s): Maraganore DM, de Andrade M, Elbaz A, Farrer MJ, Ioannidis JP, Kruger R, Rocca WA, Schneider NK, Lesnick TG, Lincoln SJ, Hulihan MM, Aasly JO, Ashizawa T, Chartier-Harlin MC, Checkoway H, Ferrarese C, Hadjigeorgiou G, Hattori N, Kawakami H, Lambert JC, Lynch T, Mellick GD, Papapetropoulos S, Parsian A, Quattrone A, Riess O, Tan EK, Van Broeckhoven C; Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16896109&query_hl=40&itool=pubmed_docsum
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Comparison of 2-dimensional magnetic resonance imaging and 3-planar reconstruction methods for targeting the subthalamic nucleus in Parkinson disease. Author(s): Andrade-Souza YM, Schwalb JM, Hamani C, Hoque T, Saint-Cyr J, Lozano AM. Source: Surgical Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15808723&query_hl=40&itool=pubmed_docsum
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Comprehensive association analysis of the NOS2A gene with Parkinson disease. Author(s): Schulte C, Sharma M, Mueller JC, Lichtner P, Prestel J, Berg D, Gasser T. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17159127&query_hl=40&itool=pubmed_docsum
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Consumption of milk and calcium in midlife and the future risk of Parkinson disease. Author(s): Park M, Ross GW, Petrovitch H, White LR, Masaki KH, Nelson JS, Tanner CM, Curb JD, Blanchette PL, Abbott RD. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15781824&query_hl=40&itool=pubmed_docsum
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Contribution of aging to the severity of different motor signs in Parkinson disease. Author(s): Levy G, Louis ED, Cote L, Perez M, Mejia-Santana H, Andrews H, Harris J, Waters C, Ford B, Frucht S, Fahn S, Marder K. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15767513&query_hl=40&itool=pubmed_docsum
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Correlation between the Overactive Bladder questionnaire (OAB-q) and urodynamic data of Parkinson disease patients affected by neurogenic detrusor overactivity during antimuscarinic treatment. Author(s): Palleschi G, Pastore AL, Stocchi F, Bova G, Inghilleri M, Sigala S, Carbone A. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16855424&query_hl=40&itool=pubmed_docsum
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Daily affect in Parkinson disease is responsive to life events and motor symptoms. Author(s): Weintraub D, Cary MS, Stern MB, Taraborelli D, Katz IR. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16473981&query_hl=40&itool=pubmed_docsum
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Daytime sleepiness and the COMT val158met polymorphism in patients with Parkinson disease. Author(s): Rissling I, Frauscher B, Kronenberg F, Tafti M, Stiasny-Kolster K, Robyr AC, Korner Y, Oertel WH, Poewe W, Hogl B, Moller JC. Source: Sleep. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16453988&query_hl=40&itool=pubmed_docsum
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Deep brain stimulation improves orthostatic regulation of patients with Parkinson disease. Author(s): Stemper B, Beric A, Welsch G, Haendl T, Sterio D, Hilz MJ. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17130410&query_hl=40&itool=pubmed_docsum
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Deep brain stimulation in Parkinson disease: a metaanalysis of patient outcomes. Author(s): Weaver F, Follett K, Hur K, Ippolito D, Stern M. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16381181&query_hl=40&itool=pubmed_docsum
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Deep brain stimulation of the subthalamic nucleus enhances emotional processing in Parkinson disease. Author(s): Schneider F, Habel U, Volkmann J, Regel S, Kornischka J, Sturm V, Freund HJ. Source: Archives of General Psychiatry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12622663&query_hl=40&itool=pubmed_docsum
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Dementia in Parkinson disease: functional imaging of cholinergic and dopaminergic pathways. Author(s): Hilker R, Thomas AV, Klein JC, Weisenbach S, Kalbe E, Burghaus L, Jacobs AH, Herholz K, Heiss WD. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16344512&query_hl=40&itool=pubmed_docsum
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Dendritic degeneration in neostriatal medium spiny neurons in Parkinson disease. Author(s): Zaja-Milatovic S, Milatovic D, Schantz AM, Zhang J, Montine KS, Samii A, Deutch AY, Montine TJ. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15699393&query_hl=40&itool=pubmed_docsum
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Depression is associated with impairment of ADL, not motor function in Parkinson disease. Author(s): Holroyd S, Currie LJ, Wooten GF. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15985588&query_hl=40&itool=pubmed_docsum
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Depression is associated with impairment of ADL, not motor function in Parkinson disease. Author(s): Iwasaki Y, Ikeda K, Igarashi O, Baba S. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16567734&query_hl=40&itool=pubmed_docsum
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Diagnosis and treatment of Parkinson disease: molecules to medicine. Author(s): Savitt JM, Dawson VL, Dawson TM. Source: The Journal of Clinical Investigation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16823471&query_hl=40&itool=pubmed_docsum
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Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease. Author(s): Gill SS, Patel NK, Hotton GR, O'Sullivan K, McCarter R, Bunnage M, Brooks DJ, Svendsen CN, Heywood P. Source: Nature Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12669033&query_hl=40&itool=pubmed_docsum
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Disease progression and pharmacodynamics in Parkinson disease - evidence for functional protection with levodopa and other treatments. Author(s): Holford NH, Chan PL, Nutt JG, Kieburtz K, Shoulson I; Parkinson Study Group. Source: Journal of Pharmacokinetics and Pharmacodynamics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16625427&query_hl=40&itool=pubmed_docsum
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Dissociating apathy and depression in Parkinson disease. Author(s): Kirsch-Darrow L, Fernandez HH, Marsiske M, Okun MS, Bowers D. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16832074&query_hl=40&itool=pubmed_docsum
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Does this patient have Parkinson disease? Author(s): Rao G, Fisch L, Srinivasan S, D'Amico F, Okada T, Eaton C, Robbins C. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12525236&query_hl=40&itool=pubmed_docsum
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Dopamine agonists and cardiac valvulopathy in Parkinson disease: a case-control study. Author(s): Yamamoto M, Uesugi T, Nakayama T. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17030757&query_hl=40&itool=pubmed_docsum
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Drug-induced psychosis in Parkinson disease: phenomenology and correlations among psychosis rating instruments. Author(s): Papapetropoulos S. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16518136&query_hl=40&itool=pubmed_docsum
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Education and occupations preceding Parkinson disease: a population-based casecontrol study. Author(s): Frigerio R, Elbaz A, Sanft KR, Peterson BJ, Bower JH, Ahlskog JE, Grossardt BR, de Andrade M, Maraganore DM, Rocca WA. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16301484&query_hl=40&itool=pubmed_docsum
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Effect of MDR1 haplotype on risk of Parkinson disease. Author(s): Tan EK, Chan DK, Ng PW, Woo J, Teo YY, Tang K, Wong LP, Chong SS, Tan C, Shen H, Zhao Y, Lee CG. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15767512&query_hl=40&itool=pubmed_docsum
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Effects of bilateral subthalamic nucleus stimulation on sleep, daytime sleepiness, and early morning dystonia in patients with Parkinson disease. Author(s): Lyons KE, Pahwa R. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16619652&query_hl=40&itool=pubmed_docsum
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Effects of caffeine on levodopa pharmacokinetics and pharmacodynamics in Parkinson disease. Author(s): Deleu D, Jacob P, Chand P, Sarre S, Colwell A. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16966563&query_hl=40&itool=pubmed_docsum
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Effects of long-term gait training using visual cues in an individual with Parkinson disease. Author(s): Sidaway B, Anderson J, Danielson G, Martin L, Smith G. Source: Physical Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16445332&query_hl=40&itool=pubmed_docsum
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Effects of Parkinson disease on two putative nondeclarative learning tasks: probabilistic classification and gambling. Author(s): Perretta JG, Pari G, Beninger RJ. Source: Cognitive and Behavioral Neurology : Official Journal of the Society for Behavioral and Cognitive Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16340390&query_hl=40&itool=pubmed_docsum
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Effects of subthalamic nucleus stimulation and levodopa treatment on gait abnormalities in Parkinson disease. Author(s): Krystkowiak P, Blatt JL, Bourriez JL, Duhamel A, Perina M, Blond S, Guieu JD, Destee A, Defebvre L. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12533092&query_hl=40&itool=pubmed_docsum
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Efficacy and safety of donepezil in the treatment of executive dysfunction in Parkinson disease: a pilot study. Author(s): Linazasoro G, Lasa A, Van Blercom N. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16062096&query_hl=40&itool=pubmed_docsum
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Efficacy and tolerability of levetiracetam in Parkinson disease patients with levodopa-induced dyskinesia. Author(s): Lyons KE, Pahwa R. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16772814&query_hl=40&itool=pubmed_docsum
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Emergence of restless legs syndrome during subthalamic stimulation for Parkinson disease. Author(s): Kedia S, Moro E, Tagliati M, Lang AE, Kumar R. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15623715&query_hl=40&itool=pubmed_docsum
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Employment as a welder and Parkinson disease among heavy equipment manufacturing workers. Author(s): Marsh GM, Gula MJ. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17033503&query_hl=40&itool=pubmed_docsum
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End-of-dose wearing off in Parkinson disease: a 9-question survey assessment. Author(s): Stacy M, Hauser R, Oertel W, Schapira A, Sethi K, Stocchi F, Tolosa E. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17095894&query_hl=40&itool=pubmed_docsum
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Excessive daytime sleepiness and subsequent development of Parkinson disease. Author(s): Abbott RD, Ross GW, White LR, Tanner CM, Masaki KH, Nelson JS, Curb JD, Petrovitch H. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16275833&query_hl=40&itool=pubmed_docsum
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Excessive daytime sleepiness in Parkinson disease: a SPECT study. Author(s): Matsui H, Nishinaka K, Oda M, Hara N, Komatsu K, Kubori T, Udaka F. Source: Sleep. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16895259&query_hl=40&itool=pubmed_docsum
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Excessive daytime sleepiness in Parkinson disease: is it the drugs or the disease? Author(s): Gjerstad MD, Alves G, Wentzel-Larsen T, Aarsland D, Larsen JP. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16966550&query_hl=40&itool=pubmed_docsum
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Experimental study of serum substantia nigra neuron autoantibody and its effect in Parkinson disease patients. Author(s): Chen J, Cao X, Xu Y, Sun S. Source: J Tongji Med Univ. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12539547&query_hl=40&itool=pubmed_docsum
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Expression patterns of retinoblastoma protein in Parkinson disease. Author(s): Jordan-Sciutto KL, Dorsey R, Chalovich EM, Hammond RR, Achim CL. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12528819&query_hl=40&itool=pubmed_docsum
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Expression profiling of substantia nigra in Parkinson disease, progressive supranuclear palsy, and frontotemporal dementia with parkinsonism. Author(s): Hauser MA, Li YJ, Xu H, Noureddine MA, Shao YS, Gullans SR, Scherzer CR, Jensen RV, McLaurin AC, Gibson JR, Scott BL, Jewett RM, Stenger JE, Schmechel DE, Hulette CM, Vance JM. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15956162&query_hl=40&itool=pubmed_docsum
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Extradural motor cortex stimulation for advanced Parkinson disease. Report of two cases. Author(s): Canavero S, Paolotti R, Bonicalzi V, Castellano G, Greco-Crasto S, Rizzo L, Davini O, Zenga F, Ragazzi P. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12450046&query_hl=40&itool=pubmed_docsum
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Factors associated with the development of motor fluctuations and dyskinesias in Parkinson disease. Author(s): Hauser RA, McDermott MP, Messing S. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17172616&query_hl=40&itool=pubmed_docsum
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Factors influencing susceptibility to compulsive dopaminergic drug use in Parkinson disease. Author(s): Evans AH, Lawrence AD, Potts J, Appel S, Lees AJ. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16301483&query_hl=40&itool=pubmed_docsum
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Failure of single-unit neuronal activity to differentiate globus pallidus internus and externus in Parkinson disease. Author(s): Schiff SJ, Dunagan BK, Worth RM. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12134901&query_hl=40&itool=pubmed_docsum
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Failure to find alpha-synuclein gene dosage changes in 190 patients with familial Parkinson disease. Author(s): Gispert S, Trenkwalder C, Mota-Vieira L, Kostic V, Auburger G. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15642855&query_hl=40&itool=pubmed_docsum
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Failures and successes of clinical trials for Parkinson disease treatments. Author(s): Dawson TM. Source: Retina (Philadelphia, Pa.). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16374349&query_hl=40&itool=pubmed_docsum
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Familial aggregation of Parkinson disease: a comparative study of early-onset and late-onset disease. Author(s): Payami H, Zareparsi S, James D, Nutt J. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12020270&query_hl=40&itool=pubmed_docsum
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Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Author(s): Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10888878&query_hl=40&itool=pubmed_docsum
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Family-based case-control study of cigarette smoking and Parkinson disease. Author(s): Scott WK, Zhang F, Stajich JM, Scott BL, Stacy MA, Vance JM. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15699372&query_hl=40&itool=pubmed_docsum
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Fetal pig neural cells for Parkinson disease. Author(s): Friedrich MJ. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10605960&query_hl=40&itool=pubmed_docsum
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Fibroblast growth factor 20 polymorphisms and haplotypes strongly influence risk of Parkinson disease. Author(s): van der Walt JM, Noureddine MA, Kittappa R, Hauser MA, Scott WK, McKay R, Zhang F, Stajich JM, Fujiwara K, Scott BL, Pericak-Vance MA, Vance JM, Martin ER. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15122513&query_hl=40&itool=pubmed_docsum
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Fluorodopa F 18 positron emission tomography and the progression of Parkinson disease. Author(s): Borghammer P, Kumakura Y, Cumming P. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16157762&query_hl=40&itool=pubmed_docsum
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Frequency of a specific cytochrome P4502D6B (CYP2D6B) mutant allele in clinically differentiated groups of patients with Parkinson disease. Author(s): Akhmedova SN, Pushnova EA, Yakimovsky AF, Avtonomov VV, Schwartz EI. Source: Biochemical and Molecular Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8581363&query_hl=40&itool=pubmed_docsum
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Frequency of dementia in Parkinson disease. Author(s): Aarsland D, Tandberg E, Larsen JP, Cummings JL. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8660156&query_hl=40&itool=pubmed_docsum
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Frequency of LRRK2 mutations in early- and late-onset Parkinson disease. Author(s): Clark LN, Wang Y, Karlins E, Saito L, Mejia-Santana H, Harris J, Louis ED, Cote LJ, Andrews H, Fahn S, Waters C, Ford B, Frucht S, Ottman R, Marder K. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17050822&query_hl=40&itool=pubmed_docsum
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Frequency, reasons, and risk factors of entacapone discontinuation in Parkinson disease. Author(s): Parashos SA, Wielinski CL, Kern JA. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15190234&query_hl=40&itool=pubmed_docsum
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Functional decline in Parkinson disease. Author(s): Jankovic J, Kapadia AS. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11594919&query_hl=40&itool=pubmed_docsum
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Functional effects of striatal dysfunction in Parkinson disease. Author(s): Holthoff-Detto VA, Kessler J, Herholz K, Bonner H, Pietrzyk U, Wurker M, Ghaemi M, Wienhard K, Wagner R, Heiss WD. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9041855&query_hl=40&itool=pubmed_docsum
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Further studies with pergolide in Parkinson disease. Author(s): Lieberman AN, Goldstein M, Gopinathan G, Leibowitz M, Neophytides A, Walker R, Hiesiger E, Nelson J. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=6889703&query_hl=40&itool=pubmed_docsum
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Gain-of-function haplotypes in the vesicular monoamine transporter promoter are protective for Parkinson disease in women. Author(s): Glatt CE, Wahner AD, White DJ, Ruiz-Linares A, Ritz B. Source: Human Molecular Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16339215&query_hl=40&itool=pubmed_docsum
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Gait analysis in patients with advanced Parkinson disease: different or additive effects on gait induced by levodopa and chronic STN stimulation. Author(s): Lubik S, Fogel W, Tronnier V, Krause M, Konig J, Jost WH. Source: Journal of Neural Transmission (Vienna, Austria : 1996). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15959852&query_hl=40&itool=pubmed_docsum
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Gait initiation in community-dwelling adults with Parkinson disease. Author(s): Andrew PD. Source: Physical Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12444883&query_hl=40&itool=pubmed_docsum
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Gambling and Parkinson disease. Author(s): Lu C, Bharmal A, Suchowersky O. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16476827&query_hl=40&itool=pubmed_docsum
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Gamma knife subthalamotomy for Parkinson disease: the subthalamic nucleus as a new radiosurgical target. Case report. Author(s): Keep MF, Mastrofrancesco L, Erdman D, Murphy B, Ashby LS. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12507103&query_hl=40&itool=pubmed_docsum
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Gastric emptying after semi-solid food in multiple system atrophy and Parkinson disease. Author(s): Thomaides T, Karapanayiotides T, Zoukos Y, Haeropoulos C, Kerezoudi E, Demacopoulos N, Floodas G, Papageorgiou E, Armakola F, Thomopoulos Y, Zaloni I. Source: Journal of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15795792&query_hl=40&itool=pubmed_docsum
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Generative naming in Parkinson disease patients. Author(s): Bayles KA, Trosset MW, Tomoeda CK, Montgomery EB Jr, Wilson J. Source: J Clin Exp Neuropsychol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8354708&query_hl=40&itool=pubmed_docsum
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Genetic evidence for ubiquitin-specific proteases USP24 and USP40 as candidate genes for late-onset Parkinson disease. Author(s): Li Y, Schrodi S, Rowland C, Tacey K, Catanese J, Grupe A. Source: Human Mutation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16917932&query_hl=40&itool=pubmed_docsum
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Genetic polymorphisms in Parkinson disease subjects with and without hallucinations: an analysis of the cholecystokinin system. Author(s): Goldman JG, Goetz CG, Berry-Kravis E, Leurgans S, Zhou L. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15313848&query_hl=40&itool=pubmed_docsum
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Genetic testing in Parkinson disease: promises and pitfalls. Author(s): Tan EK, Jankovic J. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16966499&query_hl=40&itool=pubmed_docsum
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Genetics of Parkinson disease. Author(s): Pankratz N, Foroud T. Source: Neurorx. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15717024&query_hl=40&itool=pubmed_docsum
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Genetics of Parkinson disease: paradigm shifts and future prospects. Author(s): Farrer MJ. Source: Nature Reviews. Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16543934&query_hl=40&itool=pubmed_docsum
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Genomewide association, Parkinson disease, and PARK10. Author(s): Farrer MJ, Haugarvoll K, Ross OA, Stone JT, Milkovic NM, Cobb SA, Whittle AJ, Lincoln SJ, Hulihan MM, Heckman MG, White LR, Aasly JO, Gibson JM, Gosal D, Lynch T, Wszolek ZK, Uitti RJ, Toft M. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16685661&query_hl=40&itool=pubmed_docsum
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Genomic convergence to identify candidate genes for Parkinson disease: SAGE analysis of the substantia nigra. Author(s): Noureddine MA, Li YJ, van der Walt JM, Walters R, Jewett RM, Xu H, Wang T, Walter JW, Scott BL, Hulette C, Schmechel D, Stenger JE, Dietrich F, Vance JM, Hauser MA. Source: Movement Disorders : Official Journal of the Movement Disorder Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15966006&query_hl=40&itool=pubmed_docsum
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Genotype-phenotype correlation: familial Parkinson disease. Author(s): Mori H, Hattori N, Mizuno Y. Source: Neuropathology : Official Journal of the Japanese Society of Neuropathology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12722931&query_hl=40&itool=pubmed_docsum
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Genotyping Parkinson disease-associated mitochondrial polymorphisms. Author(s): Jiang Y, Ellis T, Greenlee AR. Source: Clin Med Res. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15931342&query_hl=40&itool=pubmed_docsum
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Glial cell line-derived neurotrophic factor-supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage. Author(s): Hebb AO, Hebb K, Ramachandran AC, Mendez I. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12744369&query_hl=40&itool=pubmed_docsum
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Glial cell line-derived neurotrophic factor-supplemented hibernation of fetal ventral mesencephalic neurons for transplantation in Parkinson disease: long-term storage. Author(s): Hebb AO, Hebb K, Ramachandran AC, Mendez I. Source: Neurosurg Focus. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15769073&query_hl=40&itool=pubmed_docsum
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Glucocerebrosidase gene mutations and Parkinson disease in the Norwegian population. Author(s): Toft M, Pielsticker L, Ross OA, Aasly JO, Farrer MJ. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16476943&query_hl=40&itool=pubmed_docsum
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Great shakes: famous people with Parkinson disease. Author(s): Jones JM. Source: Southern Medical Journal. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15646755&query_hl=40&itool=pubmed_docsum
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Hallucinations in Parkinson disease in the prelevodopa era. Author(s): Fenelon G, Goetz CG, Karenberg A. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16401853&query_hl=40&itool=pubmed_docsum
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Hallucinations in Parkinson disease: neuropsychological study. Author(s): Meco G, Bonifati V, Cusimano G, Fabrizio E, Vanacore N. Source: Italian Journal of Neurological Sciences. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2246120&query_hl=40&itool=pubmed_docsum
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Heterozygosity for a mutation in the parkin gene leads to later onset Parkinson disease. Author(s): Foroud T, Uniacke SK, Liu L, Pankratz N, Rudolph A, Halter C, Shults C, Marder K, Conneally PM, Nichols WC; Parkinson Study Group. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12629236&query_hl=40&itool=pubmed_docsum
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Heterozygous PINK1 mutations: a susceptibility factor for Parkinson disease? Author(s): Djarmati A, Hedrich K, Svetel M, Lohnau T, Schwinger E, Romac S, Pramstaller PP, Kostic V, Klein C. Source: Movement Disorders : Official Journal of the Movement Disorder Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16755580&query_hl=40&itool=pubmed_docsum
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Hiccups associated with dopamine agonists in Parkinson disease. Author(s): Sharma P, Morgan JC, Sethi KD. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16534128&query_hl=40&itool=pubmed_docsum
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High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Author(s): Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16604074&query_hl=40&itool=pubmed_docsum
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High-resolution whole-genome association study of Parkinson disease. Author(s): Maraganore DM, de Andrade M, Lesnick TG, Strain KJ, Farrer MJ, Rocca WA, Pant PV, Frazer KA, Cox DR, Ballinger DG. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16252231&query_hl=40&itool=pubmed_docsum
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Homocysteine and levodopa: should Parkinson disease patients receive preventative therapy? Author(s): Postuma RB, Lang AE. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15365141&query_hl=40&itool=pubmed_docsum
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Hyperhidrosis in Parkinson disease. Author(s): Feddersen B, Klopstock T, Noachtar S. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15699402&query_hl=40&itool=pubmed_docsum
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Hyperprolactinemia may have a therapeutic role in Parkinson disease. Author(s): Login IS. Source: Annals of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7316496&query_hl=40&itool=pubmed_docsum
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Hypersexuality after pallidal surgery in Parkinson disease. Author(s): Roane DM, Yu M, Feinberg TE, Rogers JD. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12464751&query_hl=40&itool=pubmed_docsum
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Hypothalamic releasing factors and Parkinson disease. Author(s): Chase TN, Woods AC, Lipton MA, Morris CE. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=4209275&query_hl=40&itool=pubmed_docsum
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Identification and haplotype analysis of LRRK2 G2019S in Japanese patients with Parkinson disease. Author(s): Zabetian CP, Morino H, Ujike H, Yamamoto M, Oda M, Maruyama H, Izumi Y, Kaji R, Griffith A, Leis BC, Roberts JW, Yearout D, Samii A, Kawakami H. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16728648&query_hl=40&itool=pubmed_docsum
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Identification of risk and age-at-onset genes on chromosome 1p in Parkinson disease. Author(s): Oliveira SA, Li YJ, Noureddine MA, Zuchner S, Qin X, Pericak-Vance MA, Vance JM. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15986317&query_hl=40&itool=pubmed_docsum
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Identifying the pattern of olfactory deficits in Parkinson disease using the brief smell identification test. Author(s): Double KL, Rowe DB, Hayes M, Chan DK, Blackie J, Corbett A, Joffe R, Fung VS, Morris J, Halliday GM. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12707068&query_hl=40&itool=pubmed_docsum
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Immunologic diseases, anti-inflammatory drugs, and Parkinson disease: a casecontrol study. Author(s): Bower JH, Maraganore DM, Peterson BJ, Ahlskog JE, Rocca WA. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16894114&query_hl=40&itool=pubmed_docsum
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Impact of functional age on the use of dopamine agonists in patients with Parkinson disease. Author(s): Silver D. Source: The Neurologist. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16832240&query_hl=40&itool=pubmed_docsum
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Impact of gastric emptying on levodopa pharmacokinetics in Parkinson disease patients. Author(s): Muller T, Erdmann C, Bremen D, Schmidt WE, Muhlack S, Woitalla D, Goetze O. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16614536&query_hl=40&itool=pubmed_docsum
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Implications of genetics on the diagnosis and care of patients with Parkinson disease. Author(s): Klein C. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16533959&query_hl=40&itool=pubmed_docsum
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Improvement of bilateral motor functions in patients with Parkinson disease through the unilateral intraputaminal infusion of glial cell line-derived neurotrophic factor. Author(s): Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, Young B. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15739547&query_hl=40&itool=pubmed_docsum
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Incidence of Parkinson disease in Wakayama, Japan. Author(s): Morioka S, Sakata K, Yoshida S, Nakai E, Shiba M, Yoshimura N, Hashimoto T. Source: J Epidemiol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12462274&query_hl=40&itool=pubmed_docsum
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Increased incidence of Parkinson disease among relatives of patients with Gaucher disease. Author(s): Halperin A, Elstein D, Zimran A. Source: Blood Cells, Molecules & Diseases. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16651014&query_hl=40&itool=pubmed_docsum
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Increased risk for heterozygotes in recessive Parkinson disease. Author(s): Beffert U, Rosenberg RN. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16769859&query_hl=40&itool=pubmed_docsum
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Indirect-pathway neurons lose their spines in Parkinson disease. Author(s): Gerfen CR. Source: Nature Neuroscience. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16439979&query_hl=40&itool=pubmed_docsum
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Influence of heterozygosity for parkin mutation on onset age in familial Parkinson disease: the GenePD study. Author(s): Sun M, Latourelle JC, Wooten GF, Lew MF, Klein C, Shill HA, Golbe LI, Mark MH, Racette BA, Perlmutter JS, Parsian A, Guttman M, Nicholson G, Xu G, Wilk JB, Saint-Hilaire MH, DeStefano AL, Prakash R, Williamson S, Suchowersky O, Labelle N, Growdon JH, Singer C, Watts RL, Goldwurm S, Pezzoli G, Baker KB, Pramstaller PP, Burn DJ, Chinnery PF, Sherman S, Vieregge P, Litvan I, Gillis T, MacDonald ME, Myers RH, Gusella JF. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16769863&query_hl=40&itool=pubmed_docsum
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Inhaled cocaine used to relieve "off" periods in patients with Parkinson disease and unpredictable motor fluctuations: a report of 2 cases. Author(s): Di Rocco A, Nasser S, Werner P. Source: Journal of Clinical Psychopharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17110842&query_hl=40&itool=pubmed_docsum
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Initial agonist treatment of Parkinson disease: a critique. Author(s): Albin RL, Frey KA. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12580185&query_hl=40&itool=pubmed_docsum
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Initial pharmacotherapy in a population of veterans with Parkinson disease. Author(s): Swarztrauber K, Koudelka C, Brodsky MA. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16682678&query_hl=40&itool=pubmed_docsum
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Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study. Author(s): Stocchi F, Vacca L, Ruggieri S, Olanow CW. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15956161&query_hl=40&itool=pubmed_docsum
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Inverse relationship between brain noradrenaline level and dopamine loss in Parkinson disease: a possible neuroprotective role for noradrenaline. Author(s): Tong J, Hornykiewicz O, Kish SJ. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17172611&query_hl=40&itool=pubmed_docsum
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Inversion recovery MRI in idiopathic Parkinson disease is a very sensitive tool to assess neurodegeneration in the substantia nigra: preliminary investigation. Author(s): Raff U, Hutchinson M, Rojas GM, Huete I. Source: Academic Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16679274&query_hl=40&itool=pubmed_docsum
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Is decreased dexterity in Parkinson disease due to apraxia? Author(s): Landau WM, Mink JW. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17210888&query_hl=40&itool=pubmed_docsum
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JAMA patient page. Parkinson disease. Author(s): Torpy JM, Lynm C, Glass RM. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14734603&query_hl=40&itool=pubmed_docsum
Studies
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Judgment of disability stages in Parkinson disease patients due to pathological tremor of index finger. Author(s): Makabe H, Sakamoto K. Source: Electromyogr Clin Neurophysiol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11142111&query_hl=40&itool=pubmed_docsum
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Juvenile Parkinson disease and the C212Y mutation of parkin. Author(s): Ruiz-Linares A. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15023824&query_hl=40&itool=pubmed_docsum
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Keeping depression at bay helps patients with Parkinson disease. Author(s): Phillips P. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=10501101&query_hl=40&itool=pubmed_docsum
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Lack of regional selectivity during the progression of Parkinson disease: implications for pathogenesis. Author(s): Lee CS, Schulzer M, de la Fuente-Fernandez R, Mak E, Kuramoto L, Sossi V, Ruth TJ, Calne DB, Stoessl AJ. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15596613&query_hl=40&itool=pubmed_docsum
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L-dopa responsiveness in dementia with Lewy bodies, Parkinson disease with and without dementia. Author(s): Bonelli SB, Ransmayr G, Steffelbauer M, Lukas T, Lampl C, Deibl M. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15277644&query_hl=40&itool=pubmed_docsum
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Levels of alpha-synuclein mRNA in sporadic Parkinson disease patients. Author(s): Chiba-Falek O, Lopez GJ, Nussbaum RL. Source: Movement Disorders : Official Journal of the Movement Disorder Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16795004&query_hl=40&itool=pubmed_docsum
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Levodopa addiction in idiopathic Parkinson disease. Author(s): Borek LL, Friedman JH. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16275855&query_hl=40&itool=pubmed_docsum
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Parkinson Disease
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Levodopa infusion therapy in Parkinson disease: state of the art in 2004. Author(s): Nyholm D, Aquilonius SM. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15602106&query_hl=40&itool=pubmed_docsum
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Levodopa intake increases plasma levels of S-adenosylmethionine in treated patients with Parkinson disease. Author(s): Muller T, Fowler B, Kuhn W. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16340382&query_hl=40&itool=pubmed_docsum
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Levodopa-associated dyskinesia risk among Parkinson disease patients in Olmsted County, Minnesota, 1976-1990. Author(s): Van Gerpen JA, Kumar N, Bower JH, Weigand S, Ahlskog JE. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16476808&query_hl=40&itool=pubmed_docsum
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Limb-kinetic apraxia in Parkinson disease. Author(s): Quencer K, Okun MS, Crucian G, Fernandez HH, Skidmore F, Heilman KM. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17151340&query_hl=40&itool=pubmed_docsum
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Linkage disequilibrium and association of MAPT H1 in Parkinson disease. Author(s): Skipper L, Wilkes K, Toft M, Baker M, Lincoln S, Hulihan M, Ross OA, Hutton M, Aasly J, Farrer M. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15297935&query_hl=40&itool=pubmed_docsum
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Locomotor training in people with Parkinson disease. Author(s): Morris ME. Source: Physical Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17012646&query_hl=40&itool=pubmed_docsum
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Long-duration response to levodopa in patients with advanced Parkinson disease treated with subthalamic deep brain stimulation. Author(s): Wider C, Russmann H, Villemure JG, Robert B, Bogousslavsky J, Burkhard PR, Vingerhoets FJ. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16831963&query_hl=40&itool=pubmed_docsum
Studies
77
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Long-term benefits in quality of life provided by bilateral subthalamic stimulation in patients with Parkinson disease. Author(s): Lyons KE, Pahwa R. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16175854&query_hl=40&itool=pubmed_docsum
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Long-term effects of bilateral subthalamic nucleus stimulation in advanced Parkinson disease: a four year follow-up study. Author(s): Visser-Vandewalle V, van der Linden C, Temel Y, Celik H, Ackermans L, Spincemaille G, Caemaert J. Source: Parkinsonism & Related Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15823480&query_hl=40&itool=pubmed_docsum
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Long-term follow-up (24 months) of quetiapine treatment in drug-induced Parkinson disease psychosis. Author(s): Klein C, Prokhorov T, Miniovich A, Dobronevsky E, Rabey JM. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16855423&query_hl=40&itool=pubmed_docsum
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LRRK2 G2019S in families with Parkinson disease who originated from Europe and the Middle East: evidence of two distinct founding events beginning two millennia ago. Author(s): Zabetian CP, Hutter CM, Yearout D, Lopez AN, Factor SA, Griffith A, Leis BC, Bird TD, Nutt JG, Higgins DS, Roberts JW, Kay DM, Edwards KL, Samii A, Payami H. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16960813&query_hl=40&itool=pubmed_docsum
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LRRK2 gene in Parkinson disease: mutation analysis and case control association study. Author(s): Paisan-Ruiz C, Lang AE, Kawarai T, Sato C, Salehi-Rad S, Fisman GK, AlKhairallah T, St George-Hyslop P, Singleton A, Rogaeva E. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16157901&query_hl=40&itool=pubmed_docsum
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LRRK2 haplotype analyses in European and North African families with Parkinson disease: a common founder for the G2019S mutation dating from the 13th century. Author(s): Lesage S, Leutenegger AL, Ibanez P, Janin S, Lohmann E, Durr A, Brice A; French Parkinson's Disease Genetics Study Group. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16145815&query_hl=40&itool=pubmed_docsum
78
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LRRK2 mutations in Parkinson disease. Author(s): Farrer M, Stone J, Mata IF, Lincoln S, Kachergus J, Hulihan M, Strain KJ, Maraganore DM. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16157908&query_hl=40&itool=pubmed_docsum
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LRRK2 mutations in Spanish patients with Parkinson disease: frequency, clinical features, and incomplete penetrance. Author(s): Gaig C, Ezquerra M, Marti MJ, Munoz E, Valldeoriola F, Tolosa E. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16533964&query_hl=40&itool=pubmed_docsum
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LRRK2: both a cause and a risk factor for Parkinson disease? Author(s): Foroud T. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16157895&query_hl=40&itool=pubmed_docsum
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Malignant melanoma and other types of cancer preceding Parkinson disease. Author(s): Olsen JH, Friis S, Frederiksen K. Source: Epidemiology (Cambridge, Mass.). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16837822&query_hl=40&itool=pubmed_docsum
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Mitochondria in Parkinson disease: back in fashion with a little help from genetics. Author(s): Muqit MM, Gandhi S, Wood NW. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16682534&query_hl=40&itool=pubmed_docsum
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Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Author(s): van der Walt JM, Nicodemus KK, Martin ER, Scott WK, Nance MA, Watts RL, Hubble JP, Haines JL, Koller WC, Lyons K, Pahwa R, Stern MB, Colcher A, Hiner BC, Jankovic J, Ondo WG, Allen FH Jr, Goetz CG, Small GW, Mastaglia F, Stajich JM, McLaurin AC, Middleton LT, Scott BL, Schmechel DE, Pericak-Vance MA, Vance JM. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12618962&query_hl=40&itool=pubmed_docsum
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Mitochondriopathy in Parkinson disease and amyotrophic lateral sclerosis. Author(s): Martin LJ. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17146283&query_hl=40&itool=pubmed_docsum
Studies
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Modeling of the sedative and airway obstruction effects of propofol in patients with Parkinson disease undergoing stereotactic surgery. Author(s): Fabregas N, Rapado J, Gambus PL, Valero R, Carrero E, Salvador L, NaldaFelipe MA, Troconiz IF. Source: Anesthesiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12459662&query_hl=40&itool=pubmed_docsum
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Molecular pathogenesis of Parkinson disease. Author(s): Eriksen JL, Wszolek Z, Petrucelli L. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15767499&query_hl=40&itool=pubmed_docsum
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Monitoring activity in individuals with Parkinson disease: a validity study. Author(s): White DK, Wagenaar RC, Ellis T. Source: J Neurol Phys Ther. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16630367&query_hl=40&itool=pubmed_docsum
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Motor circuitry re-organization after pallidotomy in Parkinson disease: a neurophysiological study of the bereitschaftspotential, contingent negative variation, and N30. Author(s): Gironell A, Rodriguez-Fornells A, Kulisevsky J, Pascual B, Barbanoj M, Otermin P. Source: Journal of Clinical Neurophysiology : Official Publication of the American Electroencephalographic Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12488787&query_hl=40&itool=pubmed_docsum
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Motor learning and Parkinson disease: Refinement of movement velocity and endpoint excursion in a limits of stability balance task. Author(s): Jessop RT, Horowicz C, Dibble LE. Source: Neurorehabilitation and Neural Repair. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17082501&query_hl=40&itool=pubmed_docsum
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Movement-related cortical activation in familial Parkinson disease. Author(s): Delval A, Defebvre L, Labyt E, Douay X, Bourriez JL, Waucquiez N, Derambure P, Destee A. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17000986&query_hl=40&itool=pubmed_docsum
80
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Movement-related neurons of the subthalamic nucleus in patients with Parkinson disease. Author(s): Abosch A, Hutchison WD, Saint-Cyr JA, Dostrovsky JO, Lozano AM. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12450039&query_hl=40&itool=pubmed_docsum
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MR imaging of middle cerebellar peduncle width: differentiation of multiple system atrophy from Parkinson disease. Author(s): Nicoletti G, Fera F, Condino F, Auteri W, Gallo O, Pugliese P, Arabia G, Morgante L, Barone P, Zappia M, Quattrone A. Source: Radiology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16714464&query_hl=40&itool=pubmed_docsum
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Mutations in DJ-1 are rare in familial Parkinson disease. Author(s): Pankratz N, Pauciulo MW, Elsaesser VE, Marek DK, Halter CA, Wojcieszek J, Rudolph A, Shults CW, Foroud T, Nichols WC; Parkinson Study Group - PROGENI Investigators. Source: Neuroscience Letters. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16997464&query_hl=40&itool=pubmed_docsum
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Mutations in NR4A2 associated with familial Parkinson disease. Author(s): Le WD, Xu P, Jankovic J, Jiang H, Appel SH, Smith RG, Vassilatis DK. Source: Nature Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12496759&query_hl=40&itool=pubmed_docsum
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Mutations in the pantothenate kinase gene PANK2 are not associated with Parkinson disease. Author(s): Klopstock T, Elstner M, Lucking CB, Muller-Myhsok B, Gasser T, Botz E, Lichtner P, Hortnagel K. Source: Neuroscience Letters. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15843062&query_hl=40&itool=pubmed_docsum
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My dad has Parkinson disease: and my mother has boundless love. Author(s): Torrisi D. Source: The American Journal of Nursing. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15867531&query_hl=40&itool=pubmed_docsum
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Neuropathologic changes in Parkinson disease with late onset of dementia. Author(s): Jellinger KA, Seppi K, Wenning GK. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12633162&query_hl=40&itool=pubmed_docsum
Studies
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Neuroprotective therapy in Parkinson disease. Author(s): Chen S, Le W. Source: American Journal of Therapeutics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16988541&query_hl=40&itool=pubmed_docsum
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Neuropsychological effects of bilateral STN stimulation in Parkinson disease: a controlled study. Author(s): Smeding HM, Speelman JD, Koning-Haanstra M, Schuurman PR, Nijssen P, van Laar T, Schmand B. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16801645&query_hl=40&itool=pubmed_docsum
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Neurosurgery in Parkinson disease: a distressed mind in a repaired body? Author(s): Schupbach M, Gargiulo M, Welter ML, Mallet L, Behar C, Houeto JL, Maltete D, Mesnage V, Agid Y. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16801642&query_hl=40&itool=pubmed_docsum
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New pharmacologic horizons in the treatment of Parkinson disease. Author(s): Bonuccelli U, Del Dotto P. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17030738&query_hl=40&itool=pubmed_docsum
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No evidence for association with Parkinson disease for 13 single-nucleotide polymorphisms identified by whole-genome association screening. Author(s): Goris A, Williams-Gray CH, Foltynie T, Compston DA, Barker RA, Sawcer SJ. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16685662&query_hl=40&itool=pubmed_docsum
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No evidence for heritability of Parkinson disease in Swedish twins. Author(s): Lin MT, Simon DK. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15753453&query_hl=40&itool=pubmed_docsum
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Nocturnal activity with nighttime pergolide in Parkinson disease: a controlled study using actigraphy. Author(s): Comella CL, Morrissey M, Janko K. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15851743&query_hl=40&itool=pubmed_docsum
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Parkinson Disease
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Nonlinear progression of Parkinson disease as determined by serial positron emission tomographic imaging of striatal fluorodopa F 18 activity. Author(s): Hilker R, Schweitzer K, Coburger S, Ghaemi M, Weisenbach S, Jacobs AH, Rudolf J, Herholz K, Heiss WD. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15767502&query_hl=40&itool=pubmed_docsum
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Normalizing motor-related brain activity: subthalamic nucleus stimulation in Parkinson disease. Author(s): Grafton ST, Turner RS, Desmurget M, Bakay R, Delong M, Vitek J, Crutcher M. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16636237&query_hl=40&itool=pubmed_docsum
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Obstructive and restrictive pulmonary dysfunction increases disability in Parkinson disease. Author(s): Sabate M, Rodriguez M, Mendez E, Enriquez E, Gonzalez I. Source: Archives of Physical Medicine and Rehabilitation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=8554470&query_hl=40&itool=pubmed_docsum
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Olfaction differentiates parkin disease from early-onset parkinsonism and Parkinson disease. Author(s): Khan NL, Katzenschlager R, Watt H, Bhatia KP, Wood NW, Quinn N, Lees AJ. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15079034&query_hl=40&itool=pubmed_docsum
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Onset age of Parkinson disease. Author(s): Inzelberg R, Schechtman E, Paleacu D. Source: American Journal of Medical Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12210316&query_hl=40&itool=pubmed_docsum
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Optimal location of thalamotomy lesions for tremor associated with Parkinson disease: a probabilistic analysis based on postoperative magnetic resonance imaging and an integrated digital atlas. Author(s): Atkinson JD, Collins DL, Bertrand G, Peters TM, Pike GB, Sadikot AF. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12005392&query_hl=40&itool=pubmed_docsum
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Optimizing the ongoing search for new treatments for Parkinson disease: using futility designs. Author(s): Tilley BC, Palesch YY, Kieburtz K, Ravina B, Huang P, Elm JJ, Shannon K, Wooten GF, Tanner CM, Goetz GC; NET-PD Investigators. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16534099&query_hl=40&itool=pubmed_docsum
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Orthostatic hypotension in de novo Parkinson disease. Author(s): Bonuccelli U, Lucetti C, Del Dotto P, Ceravolo R, Gambaccini G, Bernardini S, Rossi G, Piaggesi A. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14568810&query_hl=40&itool=pubmed_docsum
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Parkinson disease with old-age onset: a comparative study with subjects with middleage onset. Author(s): Diederich NJ, Moore CG, Leurgans SE, Chmura TA, Goetz CG. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12707066&query_hl=40&itool=pubmed_docsum
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Pathological gambling caused by drugs used to treat Parkinson disease. Author(s): Dodd ML, Klos KJ, Bower JH, Geda YE, Josephs KA, Ahlskog JE. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16009751&query_hl=40&itool=pubmed_docsum
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Patterns of lung volume use during an extemporaneous speech task in persons with Parkinson disease. Author(s): Bunton K. Source: Journal of Communication Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15963334&query_hl=40&itool=pubmed_docsum
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Pergolide: multiple-dose pharmacokinetics in patients with mild to moderate Parkinson disease. Author(s): Thalamas C, Rajman I, Kulisevsky J, Lledo A, Mackie AE, Blin O, Gillespie TA, Seger M, Rascol O. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15965310&query_hl=40&itool=pubmed_docsum
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Plantation work and risk of Parkinson disease in a population-based longitudinal study. Author(s): Petrovitch H, Ross GW, Abbott RD, Sanderson WT, Sharp DS, Tanner CM, Masaki KH, Blanchette PL, Popper JS, Foley D, Launer L, White LR. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12433267&query_hl=40&itool=pubmed_docsum
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Practice parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Author(s): Montgomery EB Jr. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17190966&query_hl=40&itool=pubmed_docsum
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Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Author(s): Aarsland D, Emre M, Lees A, Poewe W, Ballard C. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17200503&query_hl=40&itool=pubmed_docsum
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Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study. Author(s): Aarsland D, Andersen K, Larsen JP, Lolk A, Kragh-Sorensen P. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12633150&query_hl=40&itool=pubmed_docsum
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Prognosis of Parkinson disease: risk of dementia and mortality: the Rotterdam Study. Author(s): de Lau LM, Schipper CM, Hofman A, Koudstaal PJ, Breteler MM. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16087767&query_hl=40&itool=pubmed_docsum
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Quantitative measurement of pain sensation in patients with Parkinson disease. Author(s): Djaldetti R, Shifrin A, Rogowski Z, Sprecher E, Melamed E, Yarnitsky D. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15210877&query_hl=40&itool=pubmed_docsum
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Quetiapine for insomnia in Parkinson disease: results from an open-label trial. Author(s): Juri C, Chana P, Tapia J, Kunstmann C, Parrao T. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16062098&query_hl=40&itool=pubmed_docsum
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Rare genetic mutations shed light on the pathogenesis of Parkinson disease. Author(s): Dawson TM, Dawson VL. Source: The Journal of Clinical Investigation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12531866&query_hl=40&itool=pubmed_docsum
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Reduced autonomic activity in Parkinson disease patients. Author(s): Friedman EH. Source: Stroke; a Journal of Cerebral Circulation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16917085&query_hl=40&itool=pubmed_docsum
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Reduced risk factors for vascular disorders in Parkinson disease patients: a casecontrol study. Author(s): Scigliano G, Musicco M, Soliveri P, Piccolo I, Ronchetti G, Girotti F. Source: Stroke; a Journal of Cerebral Circulation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16574924&query_hl=40&itool=pubmed_docsum
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Relationship among alpha-synuclein accumulation, dopamine synthesis, and neurodegeneration in Parkinson disease substantia nigra. Author(s): Mori F, Nishie M, Kakita A, Yoshimoto M, Takahashi H, Wakabayashi K. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16896314&query_hl=40&itool=pubmed_docsum
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Relationship between Parkinson disease with dementia and dementia with Lewy bodies. Author(s): Guo L, Itaya M, Takanashi M, Mizuno Y, Mori H. Source: Parkinsonism & Related Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15882957&query_hl=40&itool=pubmed_docsum
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Repetitive and impulsive behaviors in treated Parkinson disease. Author(s): Black KJ, Friedman JH. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17030743&query_hl=40&itool=pubmed_docsum
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Research on Parkinson disease. Author(s): Slevin JT, Gerhardt GA, Smith CD, Gash DM, Kryscio R, Young B. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15739575&query_hl=40&itool=pubmed_docsum
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Role of peroxidases in Parkinson disease: a hypothesis. Author(s): Everse J, Coates PW. Source: Free Radical Biology & Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15855048&query_hl=40&itool=pubmed_docsum
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Rotigotine transdermal patch enables rapid titration to effective doses in advancedstage idiopathic Parkinson disease: subanalysis of a parallel group, open-label, doseescalation study. Author(s): Babic T, Boothmann B, Polivka J, Rektor I, Boroojerdi B, Hack HJ, Randerath O. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16855426&query_hl=40&itool=pubmed_docsum
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Safety, tolerability, and efficacy of continuous transdermal dopaminergic stimulation with rotigotine patch in early-stage idiopathic Parkinson disease. Author(s): Guldenpfennig WM, Poole KH, Sommerville KW, Boroojerdi B. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15965307&query_hl=40&itool=pubmed_docsum
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Self-awareness of deficits in Parkinson disease. Author(s): Leritz E, Loftis C, Crucian G, Friedman W, Bowers D. Source: Clin Neuropsychol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15739807&query_hl=40&itool=pubmed_docsum
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Sex differences in clinical and genetic determinants of levodopa peak-dose dyskinesias in Parkinson disease: an exploratory study. Author(s): Zappia M, Annesi G, Nicoletti G, Arabia G, Annesi F, Messina D, Pugliese P, Spadafora P, Tarantino P, Carrideo S, Civitelli D, De Marco EV, Ciro-Candiano IC, Gambardella A, Quattrone A. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15824260&query_hl=40&itool=pubmed_docsum
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Significant linkage of Parkinson disease to chromosome 2q36-37. Author(s): Pankratz N, Nichols WC, Uniacke SK, Halter C, Rudolph A, Shults C, Conneally PM, Foroud T; Parkinson Study Group. Source: American Journal of Human Genetics. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12638082&query_hl=40&itool=pubmed_docsum
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Staging of sporadic Parkinson disease-related alpha-synuclein pathology: inter- and intra-rater reliability. Author(s): Muller CM, de Vos RA, Maurage CA, Thal DR, Tolnay M, Braak H. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16042314&query_hl=40&itool=pubmed_docsum
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Status of fetal tissue transplantation for the treatment of advanced Parkinson disease. Author(s): Greene PE, Fahn S. Source: Neurosurg Focus. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15769072&query_hl=40&itool=pubmed_docsum
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Stimulation of the subthalamic nucleus increases heart rate in patients with Parkinson disease. Author(s): Kaufmann H, Bhattacharya KF, Voustianiouk A, Gracies JM. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12451221&query_hl=40&itool=pubmed_docsum
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Subthalamic nucleus deep brain stimulation in Parkinson disease patients over age 70 years. Author(s): Tagliati M, Pourfar MH, Alterman RL. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16009925&query_hl=40&itool=pubmed_docsum
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Sudden uncontrollable somnolence and medication use in Parkinson disease. Author(s): Avorn J, Schneeweiss S, Sudarsky LR, Benner J, Kiyota Y, Levin R, Glynn RJ. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16087765&query_hl=40&itool=pubmed_docsum
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Survival study of Parkinson disease in Olmsted County, Minnesota. Author(s): Elbaz A, Bower JH, Peterson BJ, Maraganore DM, McDonnell SK, Ahlskog JE, Schaid DJ, Rocca WA. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12533094&query_hl=40&itool=pubmed_docsum
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T313M PINK1 mutation in an extended highly consanguineous Saudi family with early-onset Parkinson disease. Author(s): Chishti MA, Bohlega S, Ahmed M, Loualich A, Carroll P, Sato C, St GeorgeHyslop P, Westaway D, Rogaeva E. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17030667&query_hl=40&itool=pubmed_docsum
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Temporal lobe atrophy on MRI in Parkinson disease with dementia: a comparison with Alzheimer disease and dementia with Lewy bodies. Author(s): Tam CW, Burton EJ, McKeith IG, Burn DJ, O'Brien JT. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15753423&query_hl=40&itool=pubmed_docsum
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The effect of entacapone on homocysteine levels in Parkinson disease. Author(s): Ostrem JL, Kang GA, Subramanian I, Guarnieri M, Hubble J, Rabinowicz AL, Bronstein J. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15851757&query_hl=40&itool=pubmed_docsum
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The genetics of Parkinson disease: Implications for neurological care. Author(s): Klein C, Schlossmacher MG. Source: Nat Clin Pract Neurol. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16932540&query_hl=40&itool=pubmed_docsum
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The impact of stereotactic pallidal surgery on the dopamine D2 receptor in Parkinson disease: a positron emission tomography study. Author(s): Nakajima T, Nimura T, Yamaguchi K, Ando T, Itoh M, Yoshimoto T, Shirane R. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12546353&query_hl=40&itool=pubmed_docsum
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The importance of LRRK2 mutations in Parkinson disease. Author(s): Schapira AH. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16966498&query_hl=40&itool=pubmed_docsum
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The PINK1 phenotype can be indistinguishable from idiopathic Parkinson disease. Author(s): Albanese A, Valente EM, Romito LM, Bellacchio E, Elia AE, Dallapiccola B. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15955954&query_hl=40&itool=pubmed_docsum
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The ratio of square wave jerk rates to blink rates distinguishes progressive supranuclear palsy from Parkinson disease. Author(s): Altiparmak UE, Eggenberger E, Coleman A, Condon K. Source: Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17204917&query_hl=40&itool=pubmed_docsum
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The relation between visual hallucinations and visual evoked potential in Parkinson disease. Author(s): Matsui H, Udaka F, Tamura A, Oda M, Kubori T, Nishinaka K, Kameyama M. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15795550&query_hl=40&itool=pubmed_docsum
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Understanding Parkinson disease. Author(s): Cummings JL. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9929094&query_hl=40&itool=pubmed_docsum
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Unexplained sudden amnesia, postencephalitic Parkinson disease, subacute sclerosing panencephalitis, and Alzheimer disease: does viral synergy produce neurofibrillary tangles? Author(s): Ball MJ. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12707087&query_hl=40&itool=pubmed_docsum
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Unilateral intraputaminal glial cell line-derived neurotrophic factor in patients with Parkinson disease: response to 1 year each of treatment and withdrawal. Author(s): Slevin JT, Gash DM, Smith CD, Gerhardt GA, Kryscio R, Chebrolu H, Walton A, Wagner R, Young AB. Source: Neurosurg Focus. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16711657&query_hl=40&itool=pubmed_docsum
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Unilateral stimulation of the subthalamic nucleus in Parkinson disease: a doubleblind 12-month evaluation study. Author(s): Germano IM, Gracies JM, Weisz DJ, Tse W, Koller WC, Olanow CW. Source: Journal of Neurosurgery. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15255249&query_hl=40&itool=pubmed_docsum
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Unilateral subthalamic nucleus deep brain stimulation contralateral to thalamic stimulation in Parkinson disease. Author(s): Samii A, Slimp JC, Goodkin R. Source: Parkinsonism & Related Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15878588&query_hl=40&itool=pubmed_docsum
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Update on Parkinson disease. Author(s): Siderowf A, Stern M. Source: Annals of Internal Medicine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12693888&query_hl=40&itool=pubmed_docsum
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Update on Parkinson disease. Author(s): Lieberman AN. Source: N Y State J Med. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=3472111&query_hl=40&itool=pubmed_docsum
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Upregulation of protease-activated receptor-1 in astrocytes in Parkinson disease: astrocyte-mediated neuroprotection through increased levels of glutathione peroxidase. Author(s): Ishida Y, Nagai A, Kobayashi S, Kim SU. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16410750&query_hl=40&itool=pubmed_docsum
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Urinary 8-hydroxydeoxyguanosine levels as a biomarker for progression of Parkinson disease. Author(s): Sato S, Mizuno Y, Hattori N. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15781836&query_hl=40&itool=pubmed_docsum
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Urinary incontinence in female Parkinson disease patients. Pitfalls of diagnosis. Author(s): Khan Z, Starer P, Bhola A. Source: Urology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=2728154&query_hl=40&itool=pubmed_docsum
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Variability in spatiotemporal gait characteristics over the course of the L-dopa cycle in people with advanced Parkinson disease. Author(s): MacKay-Lyons M. Source: Physical Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9781702&query_hl=40&itool=pubmed_docsum
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Variation in the dopaminergic response during the day in Parkinson disease. Author(s): Monge A, Viselli F, Stocchi F, Barbato L, Bolner A, Modugno N, Paradiso M, Ruggieri S, Nordera G. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15190233&query_hl=40&itool=pubmed_docsum
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Viral antibodies in the sera from patients with Parkinson disease. Author(s): Marttila RJ, Arstila P, Nikoskelainen J, Halonen PE, Rinne UK. Source: European Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=323017&query_hl=40&itool=pubmed_docsum
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Viral-mediated temporally controlled dopamine production in a rat model of Parkinson disease. Author(s): Li XG, Okada T, Kodera M, Nara Y, Takino N, Muramatsu C, Ikeguchi K, Urano F, Ichinose H, Metzger D, Chambon P, Nakano I, Ozawa K, Muramatsu S. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16182609&query_hl=40&itool=pubmed_docsum
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Visual dysfunction in Parkinson disease without dementia. Author(s): Uc EY, Rizzo M, Anderson SW, Qian S, Rodnitzky RL, Dawson JD. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16282276&query_hl=40&itool=pubmed_docsum
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Visual loss as a causative factor in visual hallucinations associated with Parkinson disease. Author(s): Lepore FE. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=9236567&query_hl=40&itool=pubmed_docsum
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Visual perception in Parkinson disease dementia and dementia with Lewy bodies. Author(s): Mosimann UP, Mather G, Wesnes KA, O'Brien JT, Burn DJ, McKeith IG. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15596755&query_hl=40&itool=pubmed_docsum
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Visualizing the next steps in Parkinson disease. Author(s): Bodis-Wollner I. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12164717&query_hl=40&itool=pubmed_docsum
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Voice quality changes following phonatory-respiratory effort treatment (LSVT) versus respiratory effort treatment for individuals with Parkinson disease. Author(s): Baumgartner CA, Sapir S, Ramig TO. Source: Journal of Voice : Official Journal of the Voice Foundation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12269625&query_hl=40&itool=pubmed_docsum
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Volunteering for early phase gene transfer research in Parkinson disease. Author(s): Kim SY, Holloway RG, Frank S, Beck CA, Zimmerman C, Wilson R, Kieburtz K. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16540601&query_hl=40&itool=pubmed_docsum
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Waiting for ON: a major problem in patients with Parkinson disease and ON/OFF motor fluctuations. Author(s): Merims D, Djaldetti R, Melamed E. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12897640&query_hl=40&itool=pubmed_docsum
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Weekly drug holiday in Parkinson disease. Author(s): Goetz CG, Tanner CM, Nausieda PA. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=7031503&query_hl=40&itool=pubmed_docsum
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Welding and Parkinson disease: is there a bond? Author(s): Kieburtz K, Kurlan R. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15985564&query_hl=40&itool=pubmed_docsum
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What is the risk of sham surgery in Parkinson disease clinical trials? A review of published reports. Author(s): Frank S, Kieburtz K, Holloway R, Kim SY. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16033990&query_hl=40&itool=pubmed_docsum
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What is the risk of sham surgery in Parkinson disease clinical trials? A review of published reports. Author(s): Landau W. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16769977&query_hl=40&itool=pubmed_docsum
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When do patients with Parkinson disease disclose their diagnosis? Author(s): Haines S, Chen H, Anderson KE, Fishman PS, Shulman LM, Weiner WJ, Reich SG. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16894111&query_hl=40&itool=pubmed_docsum
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Where does Parkinson disease pathology begin in the brain? Author(s): Del Tredici K, Rub U, De Vos RA, Bohl JR, Braak H. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12030260&query_hl=40&itool=pubmed_docsum
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Which symptoms of anxiety diminish after surgical interventions for Parkinson disease? Author(s): Higginson CI, Fields JA, Troster AI. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11417665&query_hl=40&itool=pubmed_docsum
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Wild-type PINK1 prevents basal and induced neuronal apoptosis, a protective effect abrogated by Parkinson disease-related mutations. Author(s): Petit A, Kawarai T, Paitel E, Sanjo N, Maj M, Scheid M, Chen F, Gu Y, Hasegawa H, Salehi-Rad S, Wang L, Rogaeva E, Fraser P, Robinson B, St George-Hyslop P, Tandon A. Source: The Journal of Biological Chemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16079129&query_hl=40&itool=pubmed_docsum
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Young-onset Parkinson disease with and without parkin gene mutations: a fluorodopa F 18 positron emission tomography study. Author(s): Thobois S, Ribeiro MJ, Lohmann E, Durr A, Pollak P, Rascol O, Guillouet S, Chapoy E, Costes N, Agid Y, Remy P, Brice A, Broussolle E; French Parkinson's Disease Genetics Study Group. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12756135&query_hl=40&itool=pubmed_docsum
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Ziprasidone and psychosis in Parkinson disease. Author(s): Micheli F, Taubenslag N, Gatto E, Scorticati MC. Source: Clinical Neuropharmacology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16239772&query_hl=40&itool=pubmed_docsum
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Zonisamide improves motor function in Parkinson disease: a randomized, doubleblind study. Author(s): Murata M, Hasegawa K, Kanazawa I; The Japan Zonisamide on PD Study Group. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17200492&query_hl=40&itool=pubmed_docsum
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CHAPTER 2. ALTERNATIVE MEDICINE AND PARKINSON DISEASE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Parkinson disease. 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 Parkinson disease 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 Parkinson disease (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 Parkinson disease: •
Cannabis for dyskinesia in Parkinson disease: a randomized double-blind crossover study. Author(s): Carroll CB, Bain PG, Teare L, Liu X, Joint C, Wroath C, Parkin SG, Fox P, Wright D, Hobart J, Zajicek JP. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15477546&query_hl=1&itool=pubmed_docsum
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Cell survival and clinical outcome following intrastriatal transplantation in Parkinson disease. Author(s): Hagell P, Brundin P. Source: Journal of Neuropathology and Experimental Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11487048&query_hl=1&itool=pubmed_docsum
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Concise review: therapeutic strategies for Parkinson disease based on the modulation of adult neurogenesis. Author(s): Geraerts M, Krylyshkina O, Debyser Z, Baekelandt V. Source: Stem Cells (Dayton, Ohio). http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17082225&query_hl=1&itool=pubmed_docsum
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Creatine supplementation in Parkinson disease: a placebo-controlled randomized pilot trial. Author(s): Bender A, Koch W, Elstner M, Schombacher Y, Bender J, Moeschl M, Gekeler F, Muller-Myhsok B, Gasser T, Tatsch K, Klopstock T. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17030762&query_hl=1&itool=pubmed_docsum
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Dietary fatty acids and the risk of Parkinson disease: the Rotterdam study. Author(s): de Lau LM, Bornebroek M, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15985568&query_hl=1&itool=pubmed_docsum
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Dietary folate, vitamin B12, and vitamin B6 and the risk of Parkinson disease. Author(s): de Lau LM, Koudstaal PJ, Witteman JC, Hofman A, Breteler MM. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16864826&query_hl=1&itool=pubmed_docsum
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Does transcranial magnetic stimulation improve the motor symptoms of Parkinson disease? Author(s): Tsuji S, Akamatsu N. Source: Journal of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=14579125&query_hl=1&itool=pubmed_docsum
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Dopaminergic drugs restore facilitatory premotor-motor interactions in Parkinson disease. Author(s): Mir P, Matsunaga K, Gilio F, Quinn NP, Siebner HR, Rothwell JC. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15955942&query_hl=1&itool=pubmed_docsum
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Driving with distraction in Parkinson disease. Author(s): Uc EY, Rizzo M, Anderson SW, Sparks JD, Rodnitzky RL, Dawson JD. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17130409&query_hl=1&itool=pubmed_docsum
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Early descriptions of Parkinson disease in ancient China. Author(s): Zhang ZX, Dong ZH, Roman GC. Source: Archives of Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16682554&query_hl=1&itool=pubmed_docsum
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Estrogens and Parkinson disease: novel approach for neuroprotection. Author(s): Sawada H, Shimohama S. Source: Endocrine. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12777706&query_hl=1&itool=pubmed_docsum
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Experimental study on inhibition of neuronal toxical effect of levodopa by ginkgo biloba extract on Parkinson disease in rats. Author(s): Cao F, Sun S, Tong ET. Source: J Huazhong Univ Sci Technolog Med Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12973934&query_hl=1&itool=pubmed_docsum
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Experimental study on the protective effect of puerarin to Parkinson disease. Author(s): Li X, Sun S, Tong E. Source: J Huazhong Univ Sci Technolog Med Sci. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=12973933&query_hl=1&itool=pubmed_docsum
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High-frequency rTMS improves time perception in Parkinson disease. Author(s): Koch G, Oliveri M, Brusa L, Stanzione P, Torriero S, Caltagirone C. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15623713&query_hl=1&itool=pubmed_docsum
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In vivo complementation of complex I by the yeast Ndi1 enzyme. Possible application for treatment of Parkinson disease. Author(s): Seo BB, Nakamaru-Ogiso E, Flotte TR, Matsuno-Yagi A, Yagi T. Source: The Journal of Biological Chemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16543240&query_hl=1&itool=pubmed_docsum
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Parkinson disease studies yield insights. Author(s): Friedrich MJ. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15671413&query_hl=1&itool=pubmed_docsum
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Peroperative transcranial sonography for electrode placement into the targeted subthalamic nucleus of patients with Parkinson disease: technical note. Author(s): Moringlane JR, Fuss G, Becker G.
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Source: Surgical Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15639532&query_hl=1&itool=pubmed_docsum •
Postmortem brain fatty acid profile of levodopa-treated Parkinson disease patients and parkinsonian monkeys. Author(s): Julien C, Berthiaume L, Hadj-Tahar A, Rajput AH, Bedard PJ, Di Paolo T, Julien P, Calon F. Source: Neurochemistry International. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16442670&query_hl=1&itool=pubmed_docsum
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Practice Parameter: Neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology. Author(s): Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T, Weiner WJ. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16585047&query_hl=1&itool=pubmed_docsum
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Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Author(s): Montgomery EB Jr. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17210906&query_hl=1&itool=pubmed_docsum
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Practice Parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Author(s): Suchowersky O, Gronseth G, Perlmutter J, Reich S, Zesiewicz T, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16606908&query_hl=1&itool=pubmed_docsum
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Protective effect and mechanism of Ginkgo biloba leaf extracts for Parkinson disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Author(s): Yang SF, Wu Q, Sun AS, Huang XN, Shi JS. Source: Acta Pharmacologica Sinica. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11749805&query_hl=1&itool=pubmed_docsum
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Proteomic identification of a stress protein, mortalin/mthsp70/GRP75: relevance to Parkinson disease. Author(s): Jin J, Hulette C, Wang Y, Zhang T, Pan C, Wadhwa R, Zhang J.
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Source: Molecular & Cellular Proteomics : Mcp. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16565515&query_hl=1&itool=pubmed_docsum •
Research yields clues to improving cell therapy for Parkinson disease. Author(s): Friedrich MJ. Source: Jama : the Journal of the American Medical Association. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11779245&query_hl=1&itool=pubmed_docsum
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Role of cell therapy in Parkinson disease. Author(s): Lindvall O, Hagell P. Source: Neurosurg Focus. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15769071&query_hl=1&itool=pubmed_docsum
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Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication. Author(s): Panov A, Dikalov S, Shalbuyeva N, Taylor G, Sherer T, Greenamyre JT. Source: The Journal of Biological Chemistry. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16243845&query_hl=1&itool=pubmed_docsum
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rTMS of supplementary motor area modulates therapy-induced dyskinesias in Parkinson disease. Author(s): Koch G, Brusa L, Caltagirone C, Peppe A, Oliveri M, Stanzione P, Centonze D. Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16116131&query_hl=1&itool=pubmed_docsum
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Sleep disturbances in the rotenone animal model of Parkinson disease. Author(s): Garcia-Garcia F, Ponce S, Brown R, Cussen V, Krueger JM. Source: Brain Research. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15854587&query_hl=1&itool=pubmed_docsum
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Subthalamic GAD gene transfer in Parkinson disease patients who are candidates for deep brain stimulation. Author(s): During MJ, Kaplitt MG, Stern MB, Eidelberg D. Source: Human Gene Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11529246&query_hl=1&itool=pubmed_docsum
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Subthalamic nucleus stimulation modulates afferent inhibition in Parkinson disease. Author(s): Sailer A, Cunic DI, Paradiso GO, Gunraj CA, Wagle-Shukla A, Moro E, Lozano AM, Lang AE, Chen R.
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Source: Neurology. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=17261682&query_hl=1&itool=pubmed_docsum •
Suppressed sympathetic skin response in Parkinson disease. Author(s): Haapaniemi TH, Korpelainen JT, Tolonen U, Suominen K, Sotaniemi KA, Myllyla VV. Source: Clinical Autonomic Research : Official Journal of the Clinical Autonomic Research Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=11324989&query_hl=1&itool=pubmed_docsum
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Taiji for individuals with Parkinson disease and their support partners: a program evaluation. Author(s): Klein PJ, Rivers L. Source: J Neurol Phys Ther. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16630368&query_hl=1&itool=pubmed_docsum
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Temporal variability of gait in Parkinson disease: effects of a rehabilitation programme based on rhythmic sound cues. Author(s): del Olmo MF, Cudeiro J. Source: Parkinsonism & Related Disorders. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15619459&query_hl=1&itool=pubmed_docsum
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Testing functional performance in people with Parkinson disease. Author(s): Brusse KJ, Zimdars S, Zalewski KR, Steffen TM. Source: Physical Therapy. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=15679464&query_hl=1&itool=pubmed_docsum
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The sequence effect and gait festination in Parkinson disease: contributors to freezing of gait? Author(s): Iansek R, Huxham F, McGinley J. Source: Movement Disorders : Official Journal of the Movement Disorder Society. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16773644&query_hl=1&itool=pubmed_docsum
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Training with verbal instructional cues results in near-term improvement of gait in people with Parkinson disease. Author(s): Lehman DA, Toole T, Lofald D, Hirsch MA. Source: J Neurol Phys Ther. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16386155&query_hl=1&itool=pubmed_docsum
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Tutorial on maximum inspiratory and expiratory mouth pressures in individuals with idiopathic Parkinson disease (IPD) and the preliminary results of an expiratory
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muscle strength training program. Author(s): Silverman EP, Sapienza CM, Saleem A, Carmichael C, Davenport PW, Hoffman-Ruddy B, Okun MS. Source: Neurorehabilitation. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=A bstractPlus&list_uids=16720940&query_hl=1&itool=pubmed_docsum
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://health.aol.com/healthyliving/althealth
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/naturalmedicine.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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Open Directory Project: http://dmoz.org/Health/Alternative/
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to Parkinson disease; 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
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Herbs and Supplements Carbidopa Source: Healthnotes, Inc.; www.healthnotes.com Carbidopa/Levodopa 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
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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 3. BOOKS ON PARKINSON DISEASE Overview This chapter provides bibliographic book references relating to Parkinson disease. In addition to online booksellers such as www.amazon.com and www.bn.com, the National Library of Medicine is an excellent source for book titles on Parkinson disease. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for Parkinson disease at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Parkinson disease” (or a synonym) in their titles. The following is indicative of the results you might find when searching for Parkinson disease (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
100 Questions & Answers About Parkinson Disease (100 Questions & Answers about.) Abraham Lieberman (2002); ISBN: 0763704334; http://www.amazon.com/exec/obidos/ASIN/0763704334/icongroupinterna
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A Parkinson Disease Gene Discovered, an Oncogene Remembered: An article from: The Scientist Nicole Johnston (2005); ISBN: B000BGBELM; http://www.amazon.com/exec/obidos/ASIN/B000BGBELM/icongroupinterna
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A popular dietary supplement shows promise as an early Parkinson disease treatment: An article from: HealthFacts Maryann Napoli (2005); ISBN: B000BE5Q40; http://www.amazon.com/exec/obidos/ASIN/B000BE5Q40/icongroupinterna
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Acoustic analysis of clear versus conversational speech in individuals with Parkinson disease A.M. Goberman and L.W. Elmer; ISBN: B000M5M8AI; http://www.amazon.com/exec/obidos/ASIN/B000M5M8AI/icongroupinterna
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Biceps pain as the presenting symptom of Parkinson disease: effective treatment with L-dopa.(Case Report): An article from: Southern Medical Journal Gordon J. Gilbert (2005); ISBN: B0008426QY; http://www.amazon.com/exec/obidos/ASIN/B0008426QY/icongroupinterna
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Depression: a primary symptom of Parkinson Disease?: An article from: The Journal of Rehabilitation Franklin H. Silverman and Barbara Henry (2005); ISBN: B0008MFKVE; http://www.amazon.com/exec/obidos/ASIN/B0008MFKVE/icongroupinterna
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Detection of preclinical Parkinson disease in at-risk family members with use of [123I] beta-CIT and SPECT: An exploratory study : An article from: Mayo Clinic Proceedings Demetrius M Maraganore, Michael K O'Connor, James H Bower, and Karen M Kuntz (2005); ISBN: B000B5ESXY; http://www.amazon.com/exec/obidos/ASIN/B000B5ESXY/icongroupinterna
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Developmental pesticide models of the Parkinson disease phenotype.(Research / Mini-Monograph) : An article from: Environmental Health Perspectives Deborah A. Cory-Slechta, Mona Thiruchelvam, Brian K. Barlow, and Eric K. Richfield (2005); ISBN: B000BQGQHE; http://www.amazon.com/exec/obidos/ASIN/B000BQGQHE/icongroupinterna
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Enza Maria Valente: Pursuing Parkinson Disease : An article from: The Scientist Eugene Russo (2006); ISBN: B000FEC35Q; http://www.amazon.com/exec/obidos/ASIN/B000FEC35Q/icongroupinterna
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Fundamental frequency (F0) measures comparing speech tasks in aphasia and Parkinson disease. : An article from: Journal of Medical Speech - Language Pathology Diana Van Lancker Sidtis, Wayne Hanson, Catherine Jackson, and Andrew Lanto (2005); ISBN: B0009GTE0C; http://www.amazon.com/exec/obidos/ASIN/B0009GTE0C/icongroupinterna
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Gale Encyclopedia of Medicine: Parkinson disease Laith Farid Gulli M.D. (2004); ISBN: B00075V1L0; http://www.amazon.com/exec/obidos/ASIN/B00075V1L0/icongroupinterna
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Great shakes: famous people with Parkinson disease.(Original Article): An article from: Southern Medical Journal Jeffrey M. Jones (2005); ISBN: B00081WS56; http://www.amazon.com/exec/obidos/ASIN/B00081WS56/icongroupinterna
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Jaw and finger movements during visual and auditory motor tracking in Parkinson disease.: An article from: Journal of Medical Speech - Language Pathology Scott G. Adams, Mandar Jog, T. Eadie, and A. Dykstra (2005); ISBN: B0009GTDWQ; http://www.amazon.com/exec/obidos/ASIN/B0009GTDWQ/icongroupinterna
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Joining forces to understand Parkinson disease.(NIEHS Extramural Update) : An article from: Environmental Health Perspectives (2005); ISBN: B0009H3LIC; http://www.amazon.com/exec/obidos/ASIN/B0009H3LIC/icongroupinterna
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Medical services utilization and prognosis in Parkinson disease: A population-based study : An article from: Mayo Clinic Proceedings Sotirios A Parashos, Demetrius M Maraganore, Peter C O'Brien, and Walter A Rocca (2005); ISBN: B000BE3J8A; http://www.amazon.com/exec/obidos/ASIN/B000BE3J8A/icongroupinterna
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Pesticides and Parkinson disease.(Neurology) : An article from: Environmental Health Perspectives Renee Twombly (2005); ISBN: B000BR6KKQ; http://www.amazon.com/exec/obidos/ASIN/B000BR6KKQ/icongroupinterna
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Reliability of speech intelligibility ratings using the Unified Parkinson Disease Rating Scale.: An article from: Journal of Medical Speech - Language Pathology Richard I. Zraick, Tara M. Dennie, Samer D. Tabbal, and Terri J. Hutton (2005); ISBN: B0008IRJI0; http://www.amazon.com/exec/obidos/ASIN/B0008IRJI0/icongroupinterna
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Respiratory function and variability in individuals with Parkinson disease: pre- and post-Lee Silverman Voice Treatment.: An article from: Journal of Medical Speech Language Pathology Jessica E. Huber, Elaine T. Stathopoulos, Lorraine O. Ramig, and Sandi L. Lancaster (2005); ISBN: B0008IRJH6; http://www.amazon.com/exec/obidos/ASIN/B0008IRJH6/icongroupinterna
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Service delivery variables and outcomes of treatment for hypokinetic dysarthria in Parkinson disease.: An article from: Journal of Medical Speech - Language Pathology Amy B. Wohlert (2005); ISBN: B0009GTE1G; http://www.amazon.com/exec/obidos/ASIN/B0009GTE1G/icongroupinterna
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Shaking Up Parkinson Disease: Fighting Like a Tiger, Thinking Like a Fox Abraham Lieberman (2001); ISBN: 0763718661; http://www.amazon.com/exec/obidos/ASIN/0763718661/icongroupinterna
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Susceptibility of speakers with Parkinson disease to delayed feedback.: An article from: Journal of Medical Speech - Language Pathology Bernard Rousseau and Christopher R. Watts (2005); ISBN: B0008FR3CA; http://www.amazon.com/exec/obidos/ASIN/B0008FR3CA/icongroupinterna
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The Comfort of Home for Parkinson Disease: A Guide for Caregivers (The Comfort of Home) Maria M. Meyer, Paula Derr, and Susan C. Imke (2007); ISBN: 0966476778; http://www.amazon.com/exec/obidos/ASIN/0966476778/icongroupinterna
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The effects of delayed and frequency shifted feedback on speakers with Parkinson disease.: An article from: Journal of Medical Speech - Language Pathology Bettina Brendel, Anja Lowit, and Peter Howell (2005); ISBN: B0009GTDX0; http://www.amazon.com/exec/obidos/ASIN/B0009GTDX0/icongroupinterna
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The role of early life environmental risk factors in Parkinson disease: what is the evidence?(Research / Mini-Monograph): An article from: Environmental Health Perspectives Giancarlo Logroscino (2005); ISBN: B000BQGQG0; http://www.amazon.com/exec/obidos/ASIN/B000BQGQG0/icongroupinterna
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APPENDICES
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APPENDIX A. HELP ME UNDERSTAND GENETICS Overview This appendix presents basic information about genetics in clear language and provides links to online resources.14
The Basics: Genes and How They Work This section gives you information on the basics of cells, DNA, genes, chromosomes, and proteins. What Is a Cell? Cells are the basic building blocks of all living things. The human body is composed of trillions of cells. They provide structure for the body, take in nutrients from food, convert those nutrients into energy, and carry out specialized functions. Cells also contain the body’s hereditary material and can make copies of themselves. Cells have many parts, each with a different function. Some of these parts, called organelles, are specialized structures that perform certain tasks within the cell. Human cells contain the following major parts, listed in alphabetical order: •
Cytoplasm: The cytoplasm is fluid inside the cell that surrounds the organelles.
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Endoplasmic reticulum (ER): This organelle helps process molecules created by the cell and transport them to their specific destinations either inside or outside the cell.
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Golgi apparatus: The golgi apparatus packages molecules processed by the endoplasmic reticulum to be transported out of the cell.
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Lysosomes and peroxisomes: These organelles are the recycling center of the cell. They digest foreign bacteria that invade the cell, rid the cell of toxic substances, and recycle worn-out cell components.
14 This appendix is an excerpt from the National Library of Medicine’s handbook, Help Me Understand Genetics. For the full text of the Help Me Understand Genetics handbook, see http://ghr.nlm.nih.gov/handbook.
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•
Mitochondria: Mitochondria are complex organelles that convert energy from food into a form that the cell can use. They have their own genetic material, separate from the DNA in the nucleus, and can make copies of themselves.
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Nucleus: The nucleus serves as the cell’s command center, sending directions to the cell to grow, mature, divide, or die. It also houses DNA (deoxyribonucleic acid), the cell’s hereditary material. The nucleus is surrounded by a membrane called the nuclear envelope, which protects the DNA and separates the nucleus from the rest of the cell.
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Plasma membrane: The plasma membrane is the outer lining of the cell. It separates the cell from its environment and allows materials to enter and leave the cell.
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Ribosomes: Ribosomes are organelles that process the cell’s genetic instructions to create proteins. These organelles can float freely in the cytoplasm or be connected to the endoplasmic reticulum. What Is DNA?
DNA, or deoxyribonucleic acid, is the hereditary material in humans and almost all other organisms. Nearly every cell in a person’s body has the same DNA. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). The information in DNA is stored as a code made up of four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). Human DNA consists of about 3 billion bases, and more than 99 percent of those bases are the same in all people. The order, or sequence, of these bases determines the information available for building and maintaining an organism, similar to the way in which letters of the alphabet appear in a certain order to form words and sentences. DNA bases pair up with each other, A with T and C with G, to form units called base pairs. Each base is also attached to a sugar molecule and a phosphate molecule. Together, a base, sugar, and phosphate are called a nucleotide. Nucleotides are arranged in two long strands that form a spiral called a double helix. The structure of the double helix is somewhat like a ladder, with the base pairs forming the ladder’s rungs and the sugar and phosphate molecules forming the vertical sidepieces of the ladder. An important property of DNA is that it can replicate, or make copies of itself. Each strand of DNA in the double helix can serve as a pattern for duplicating the sequence of bases. This is critical when cells divide because each new cell needs to have an exact copy of the DNA present in the old cell.
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DNA is a double helix formed by base pairs attached to a sugar-phosphate backbone. What Is Mitochondrial DNA? Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA. This genetic material is known as mitochondrial DNA or mtDNA. Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Each cell contains hundreds to thousands of mitochondria, which are located in the fluid that surrounds the nucleus (the cytoplasm). Mitochondria produce energy through a process called oxidative phosphorylation. This process uses oxygen and simple sugars to create adenosine triphosphate (ATP), the cell’s main energy source. A set of enzyme complexes, designated as complexes I-V, carry out oxidative phosphorylation within mitochondria. In addition to energy production, mitochondria play a role in several other cellular activities. For example, mitochondria help regulate the self-destruction of cells (apoptosis). They are also necessary for the production of substances such as cholesterol and heme (a component of hemoglobin, the molecule that carries oxygen in the blood). Mitochondrial DNA contains 37 genes, all of which are essential for normal mitochondrial function. Thirteen of these genes provide instructions for making enzymes involved in oxidative phosphorylation. The remaining genes provide instructions for making molecules called transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs), which are chemical cousins of
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DNA. These types of RNA help assemble protein building blocks (amino acids) into functioning proteins. What Is a Gene? A gene is the basic physical and functional unit of heredity. Genes, which are made up of DNA, act as instructions to make molecules called proteins. In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases. The Human Genome Project has estimated that humans have between 20,000 and 25,000 genes. Every person has two copies of each gene, one inherited from each parent. Most genes are the same in all people, but a small number of genes (less than 1 percent of the total) are slightly different between people. Alleles are forms of the same gene with small differences in their sequence of DNA bases. These small differences contribute to each person’s unique physical features.
Genes are made up of DNA. Each chromosome contains many genes. What Is a Chromosome? In the nucleus of each cell, the DNA molecule is packaged into thread-like structures called chromosomes. Each chromosome is made up of DNA tightly coiled many times around proteins called histones that support its structure. Chromosomes are not visible in the cell’s nucleus—not even under a microscope—when the cell is not dividing. However, the DNA that makes up chromosomes becomes more tightly packed during cell division and is then visible under a microscope. Most of what researchers know about chromosomes was learned by observing chromosomes during cell division. Each chromosome has a constriction point called the centromere, which divides the chromosome into two sections, or “arms.” The short arm of the chromosome is labeled the “p arm.” The long arm of the chromosome is labeled the “q arm.” The location of the centromere on each chromosome gives the chromosome its characteristic shape, and can be used to help describe the location of specific genes.
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DNA and histone proteins are packaged into structures called chromosomes. How Many Chromosomes Do People Have? In humans, each cell normally contains 23 pairs of chromosomes, for a total of 46. Twentytwo of these pairs, called autosomes, look the same in both males and females. The 23rd pair, the sex chromosomes, differ between males and females. Females have two copies of the X chromosome, while males have one X and one Y chromosome.
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The 22 autosomes are numbered by size. The other two chromosomes, X and Y, are the sex chromosomes. This picture of the human chromosomes lined up in pairs is called a karyotype. How Do Geneticists Indicate the Location of a Gene? Geneticists use maps to describe the location of a particular gene on a chromosome. One type of map uses the cytogenetic location to describe a gene’s position. The cytogenetic location is based on a distinctive pattern of bands created when chromosomes are stained with certain chemicals. Another type of map uses the molecular location, a precise description of a gene’s position on a chromosome. The molecular location is based on the sequence of DNA building blocks (base pairs) that make up the chromosome. Cytogenetic Location Geneticists use a standardized way of describing a gene’s cytogenetic location. In most cases, the location describes the position of a particular band on a stained chromosome: 17q12 It can also be written as a range of bands, if less is known about the exact location: 17q12-q21 The combination of numbers and letters provide a gene’s “address” on a chromosome. This address is made up of several parts: •
The chromosome on which the gene can be found. The first number or letter used to describe a gene’s location represents the chromosome. Chromosomes 1 through 22 (the autosomes) are designated by their chromosome number. The sex chromosomes are designated by X or Y.
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•
The arm of the chromosome. Each chromosome is divided into two sections (arms) based on the location of a narrowing (constriction) called the centromere. By convention, the shorter arm is called p, and the longer arm is called q. The chromosome arm is the second part of the gene’s address. For example, 5q is the long arm of chromosome 5, and Xp is the short arm of the X chromosome.
•
The position of the gene on the p or q arm. The position of a gene is based on a distinctive pattern of light and dark bands that appear when the chromosome is stained in a certain way. The position is usually designated by two digits (representing a region and a band), which are sometimes followed by a decimal point and one or more additional digits (representing sub-bands within a light or dark area). The number indicating the gene position increases with distance from the centromere. For example: 14q21 represents position 21 on the long arm of chromosome 14. 14q21 is closer to the centromere than 14q22.
Sometimes, the abbreviations “cen” or “ter” are also used to describe a gene’s cytogenetic location. “Cen” indicates that the gene is very close to the centromere. For example, 16pcen refers to the short arm of chromosome 16 near the centromere. “Ter” stands for terminus, which indicates that the gene is very close to the end of the p or q arm. For example, 14qter refers to the tip of the long arm of chromosome 14. (“Tel” is also sometimes used to describe a gene’s location. “Tel” stands for telomeres, which are at the ends of each chromosome. The abbreviations “tel” and “ter” refer to the same location.)
The CFTR gene is located on the long arm of chromosome 7 at position 7q31.2.
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Molecular Location The Human Genome Project, an international research effort completed in 2003, determined the sequence of base pairs for each human chromosome. This sequence information allows researchers to provide a more specific address than the cytogenetic location for many genes. A gene’s molecular address pinpoints the location of that gene in terms of base pairs. For example, the molecular location of the APOE gene on chromosome 19 begins with base pair 50,100,901 and ends with base pair 50,104,488. This range describes the gene’s precise position on chromosome 19 and indicates the size of the gene (3,588 base pairs). Knowing a gene’s molecular location also allows researchers to determine exactly how far the gene is from other genes on the same chromosome. Different groups of researchers often present slightly different values for a gene’s molecular location. Researchers interpret the sequence of the human genome using a variety of methods, which can result in small differences in a gene’s molecular address. For example, the National Center for Biotechnology Information (NCBI) identifies the molecular location of the APOE gene as base pair 50,100,901 to base pair 50,104,488 on chromosome 19. The Ensembl database identifies the location of this gene as base pair 50,100,879 to base pair 50,104,489 on chromosome 19. Neither of these addresses is incorrect; they represent different interpretations of the same data. For consistency, Genetics Home Reference presents data from NCBI for the molecular location of genes. What Are Proteins and What Do They Do? Proteins are large, complex molecules that play many critical roles in the body. They do most of the work in cells and are required for the structure, function, and regulation of the body’s tissues and organs. Proteins are made up of hundreds or thousands of smaller units called amino acids, which are attached to one another in long chains. There are 20 different types of amino acids that can be combined to make a protein. The sequence of amino acids determines each protein’s unique 3-dimensional structure and its specific function.
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Examples of Protein Functions Proteins can be described according to their large range of functions in the body, listed in alphabetical order: Function Antibody
Description Antibodies bind to specific foreign particles, such as viruses and bacteria, to help protect the body.
Example Immunoglobulin G (IgG)
Enzyme
Enzymes carry out almost all of the thousands of chemical reactions that take place in cells. They also assist with the formation of new molecules by reading the genetic information stored in DNA.
Phenylalanine hydroxylase
Messenger
Messenger proteins, such as some types of hormones, transmit signals to coordinate biological processes between different cells, tissues, and organs.
Growth hormone
Structural component
These proteins provide structure and support for cells. On a larger scale, they also allow the body to move. These proteins bind and carry atoms and small molecules within cells and throughout the body.
Actin
Transport/storage
Ferritin
How Does a Gene Make a Protein? Most genes contain the information needed to make functional molecules called proteins. (A few genes produce other molecules that help the cell assemble proteins.) The journey from gene to protein is complex and tightly controlled within each cell. It consists of two major steps: transcription and translation. Together, transcription and translation are known as gene expression. During the process of transcription, the information stored in a gene’s DNA is transferred to a similar molecule called RNA (ribonucleic acid) in the cell nucleus. Both RNA and DNA are made up of a chain of nucleotide bases, but they have slightly different chemical properties. The type of RNA that contains the information for making a protein is called messenger RNA (mRNA) because it carries the information, or message, from the DNA out of the nucleus into the cytoplasm. Translation, the second step in getting from a gene to a protein, takes place in the cytoplasm. The mRNA interacts with a specialized complex called a ribosome, which “reads” the sequence of mRNA bases. Each sequence of three bases, called a codon, usually codes for
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one particular amino acid. (Amino acids are the building blocks of proteins.) A type of RNA called transfer RNA (tRNA) assembles the protein, one amino acid at a time. Protein assembly continues until the ribosome encounters a “stop” codon (a sequence of three bases that does not code for an amino acid). The flow of information from DNA to RNA to proteins is one of the fundamental principles of molecular biology. It is so important that it is sometimes called the “central dogma.”
Through the processes of transcription and translation, information from genes is used to make proteins.
Can Genes Be Turned On and Off in Cells? Each cell expresses, or turns on, only a fraction of its genes. The rest of the genes are repressed, or turned off. The process of turning genes on and off is known as gene regulation. Gene regulation is an important part of normal development. Genes are turned on and off in different patterns during development to make a brain cell look and act different from a liver cell or a muscle cell, for example. Gene regulation also allows cells to react quickly to changes in their environments. Although we know that the regulation of genes is critical for life, this complex process is not yet fully understood. Gene regulation can occur at any point during gene expression, but most commonly occurs at the level of transcription (when the information in a gene’s DNA is transferred to mRNA). Signals from the environment or from other cells activate proteins called transcription factors. These proteins bind to regulatory regions of a gene and increase or decrease the level of transcription. By controlling the level of transcription, this process can determine the amount of protein product that is made by a gene at any given time.
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How Do Cells Divide? There are two types of cell division: mitosis and meiosis. Most of the time when people refer to “cell division,” they mean mitosis, the process of making new body cells. Meiosis is the type of cell division that creates egg and sperm cells. Mitosis is a fundamental process for life. During mitosis, a cell duplicates all of its contents, including its chromosomes, and splits to form two identical daughter cells. Because this process is so critical, the steps of mitosis are carefully controlled by a number of genes. When mitosis is not regulated correctly, health problems such as cancer can result. The other type of cell division, meiosis, ensures that humans have the same number of chromosomes in each generation. It is a two-step process that reduces the chromosome number by half—from 46 to 23—to form sperm and egg cells. When the sperm and egg cells unite at conception, each contributes 23 chromosomes so the resulting embryo will have the usual 46. Meiosis also allows genetic variation through a process of DNA shuffling while the cells are dividing.
Mitosis and meiosis, the two types of cell division. How Do Genes Control the Growth and Division of Cells? A variety of genes are involved in the control of cell growth and division. The cell cycle is the cell’s way of replicating itself in an organized, step-by-step fashion. Tight regulation of this process ensures that a dividing cell’s DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. The cycle has checkpoints (also called restriction points), which allow certain genes to check for mistakes and halt the cycle for repairs if something goes wrong.
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If a cell has an error in its DNA that cannot be repaired, it may undergo programmed cell death (apoptosis). Apoptosis is a common process throughout life that helps the body get rid of cells it doesn’t need. Cells that undergo apoptosis break apart and are recycled by a type of white blood cell called a macrophage. Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues. Cancer results from a disruption of the normal regulation of the cell cycle. When the cycle proceeds without control, cells can divide without order and accumulate genetic defects that can lead to a cancerous tumor.
Genetic Mutations and Health This section presents basic information about gene mutations, chromosomal changes, and conditions that run in families.15 What Is a Gene Mutation and How Do Mutations Occur? A gene mutation is a permanent change in the DNA sequence that makes up a gene. Mutations range in size from a single DNA building block (DNA base) to a large segment of a chromosome. Gene mutations occur in two ways: they can be inherited from a parent or acquired during a person’s lifetime. Mutations that are passed from parent to child are called hereditary mutations or germline mutations (because they are present in the egg and sperm cells, which are also called germ cells). This type of mutation is present throughout a person’s life in virtually every cell in the body. Mutations that occur only in an egg or sperm cell, or those that occur just after fertilization, are called new (de novo) mutations. De novo mutations may explain genetic disorders in which an affected child has a mutation in every cell, but has no family history of the disorder. Acquired (or somatic) mutations occur in the DNA of individual cells at some time during a person’s life. These changes can be caused by environmental factors such as ultraviolet radiation from the sun, or can occur if a mistake is made as DNA copies itself during cell division. Acquired mutations in somatic cells (cells other than sperm and egg cells) cannot be passed on to the next generation. Mutations may also occur in a single cell within an early embryo. As all the cells divide during growth and development, the individual will have some cells with the mutation and some cells without the genetic change. This situation is called mosaicism. Some genetic changes are very rare; others are common in the population. Genetic changes that occur in more than 1 percent of the population are called polymorphisms. They are common enough to be considered a normal variation in the DNA. Polymorphisms are 15
This section has been adapted from the National Library of Medicine’s handbook, Help Me Understand Genetics, which presents basic information about genetics in clear language and provides links to online resources: http://ghr.nlm.nih.gov/handbook.
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responsible for many of the normal differences between people such as eye color, hair color, and blood type. Although many polymorphisms have no negative effects on a person’s health, some of these variations may influence the risk of developing certain disorders. How Can Gene Mutations Affect Health and Development? To function correctly, each cell depends on thousands of proteins to do their jobs in the right places at the right times. Sometimes, gene mutations prevent one or more of these proteins from working properly. By changing a gene’s instructions for making a protein, a mutation can cause the protein to malfunction or to be missing entirely. When a mutation alters a protein that plays a critical role in the body, it can disrupt normal development or cause a medical condition. A condition caused by mutations in one or more genes is called a genetic disorder. In some cases, gene mutations are so severe that they prevent an embryo from surviving until birth. These changes occur in genes that are essential for development, and often disrupt the development of an embryo in its earliest stages. Because these mutations have very serious effects, they are incompatible with life. It is important to note that genes themselves do not cause disease—genetic disorders are caused by mutations that make a gene function improperly. For example, when people say that someone has “the cystic fibrosis gene,” they are usually referring to a mutated version of the CFTR gene, which causes the disease. All people, including those without cystic fibrosis, have a version of the CFTR gene. Do All Gene Mutations Affect Health and Development? No, only a small percentage of mutations cause genetic disorders—most have no impact on health or development. For example, some mutations alter a gene’s DNA base sequence but do not change the function of the protein made by the gene. Often, gene mutations that could cause a genetic disorder are repaired by certain enzymes before the gene is expressed (makes a protein). Each cell has a number of pathways through which enzymes recognize and repair mistakes in DNA. Because DNA can be damaged or mutated in many ways, DNA repair is an important process by which the body protects itself from disease. A very small percentage of all mutations actually have a positive effect. These mutations lead to new versions of proteins that help an organism and its future generations better adapt to changes in their environment. For example, a beneficial mutation could result in a protein that protects the organism from a new strain of bacteria. For More Information about DNA Repair and the Health Effects of Gene Mutations •
The University of Utah Genetic Science Learning Center provides information about genetic disorders that explains why some mutations cause disorders but others do not. (Refer to the questions in the far right column.) See http://learn.genetics.utah.edu/units/disorders/whataregd/.
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Additional information about DNA repair is available from the NCBI Science Primer. In the chapter called “What Is A Cell?”, scroll down to the heading “DNA Repair Mechanisms.” See http://www.ncbi.nlm.nih.gov/About/primer/genetics_cell.html. What Kinds of Gene Mutations Are Possible?
The DNA sequence of a gene can be altered in a number of ways. Gene mutations have varying effects on health, depending on where they occur and whether they alter the function of essential proteins. The types of mutations include: •
Missense mutation: This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.
•
Nonsense mutation: A nonsense mutation is also a change in one DNA base pair. Instead of substituting one amino acid for another, however, the altered DNA sequence prematurely signals the cell to stop building a protein. This type of mutation results in a shortened protein that may function improperly or not at all.
•
Insertion: An insertion changes the number of DNA bases in a gene by adding a piece of DNA. As a result, the protein made by the gene may not function properly.
•
Deletion: A deletion changes the number of DNA bases by removing a piece of DNA. Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes. The deleted DNA may alter the function of the resulting protein(s).
•
Duplication: A duplication consists of a piece of DNA that is abnormally copied one or more times. This type of mutation may alter the function of the resulting protein.
•
Frameshift mutation: This type of mutation occurs when the addition or loss of DNA bases changes a gene’s reading frame. A reading frame consists of groups of 3 bases that each code for one amino acid. A frameshift mutation shifts the grouping of these bases and changes the code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions, and duplications can all be frameshift mutations.
•
Repeat expansion: Nucleotide repeats are short DNA sequences that are repeated a number of times in a row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a mutation that increases the number of times that the short DNA sequence is repeated. This type of mutation can cause the resulting protein to function improperly. Can Changes in Chromosomes Affect Health and Development?
Changes that affect entire chromosomes or segments of chromosomes can cause problems with growth, development, and function of the body’s systems. These changes can affect many genes along the chromosome and alter the proteins made by those genes. Conditions caused by a change in the number or structure of chromosomes are known as chromosomal disorders. Human cells normally contain 23 pairs of chromosomes, for a total of 46 chromosomes in each cell. A change in the number of chromosomes leads to a chromosomal disorder. These
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changes can occur during the formation of reproductive cells (eggs and sperm) or in early fetal development. A gain or loss of chromosomes from the normal 46 is called aneuploidy. The most common form of aneuploidy is trisomy, or the presence of an extra chromosome in each cell. “Tri-” is Greek for “three”; people with trisomy have three copies of a particular chromosome in each cell instead of the normal two copies. Down syndrome is an example of a condition caused by trisomy—people with Down syndrome typically have three copies of chromosome 21 in each cell, for a total of 47 chromosomes per cell. Monosomy, or the loss of one chromosome from each cell, is another kind of aneuploidy. “Mono-” is Greek for “one”; people with monosomy have one copy of a particular chromosome in each cell instead of the normal two copies. Turner syndrome is a condition caused by monosomy. Women with Turner syndrome are often missing one copy of the X chromosome in every cell, for a total of 45 chromosomes per cell. Chromosomal disorders can also be caused by changes in chromosome structure. These changes are caused by the breakage and reunion of chromosome segments when an egg or sperm cell is formed or in early fetal development. Pieces of DNA can be rearranged within one chromosome, or transferred between two or more chromosomes. The effects of structural changes depend on their size and location. Many different structural changes are possible; some cause medical problems, while others may have no effect on a person’s health. Many cancer cells also have changes in their chromosome number or structure. These changes most often occur in somatic cells (cells other than eggs and sperm) during a person’s lifetime. Can Changes in Mitochondrial DNA Affect Health and Development? Mitochondria are structures within cells that convert the energy from food into a form that cells can use. Although most DNA is packaged in chromosomes within the nucleus, mitochondria also have a small amount of their own DNA (known as mitochondrial DNA or mtDNA). In some cases, inherited changes in mitochondrial DNA can cause problems with growth, development, and function of the body’s systems. These mutations disrupt the mitochondria’s ability to generate energy efficiently for the cell. Conditions caused by mutations in mitochondrial DNA often involve multiple organ systems. The effects of these conditions are most pronounced in organs and tissues that require a lot of energy (such as the heart, brain, and muscles). Although the health consequences of inherited mitochondrial DNA mutations vary widely, frequently observed features include muscle weakness and wasting, problems with movement, diabetes, kidney failure, heart disease, loss of intellectual functions (dementia), hearing loss, and abnormalities involving the eyes and vision. Mitochondrial DNA is also prone to noninherited (somatic) mutations. Somatic mutations occur in the DNA of certain cells during a person’s lifetime, and typically are not passed to future generations. Because mitochondrial DNA has a limited ability to repair itself when it is damaged, these mutations tend to build up over time. A buildup of somatic mutations in mitochondrial DNA has been associated with some forms of cancer and an increased risk of certain age-related disorders such as heart disease, Alzheimer disease, and Parkinson
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disease. Additionally, research suggests that the progressive accumulation of these mutations over a person’s lifetime may play a role in the normal process of aging. What Are Complex or Multifactorial Disorders? Researchers are learning that nearly all conditions and diseases have a genetic component. Some disorders, such as sickle cell anemia and cystic fibrosis, are caused by mutations in a single gene. The causes of many other disorders, however, are much more complex. Common medical problems such as heart disease, diabetes, and obesity do not have a single genetic cause—they are likely associated with the effects of multiple genes in combination with lifestyle and environmental factors. Conditions caused by many contributing factors are called complex or multifactorial disorders. Although complex disorders often cluster in families, they do not have a clear-cut pattern of inheritance. This makes it difficult to determine a person’s risk of inheriting or passing on these disorders. Complex disorders are also difficult to study and treat because the specific factors that cause most of these disorders have not yet been identified. By 2010, however, researchers predict they will have found the major contributing genes for many common complex disorders. What Information about a Genetic Condition Can Statistics Provide? Statistical data can provide general information about how common a condition is, how many people have the condition, or how likely it is that a person will develop the condition. Statistics are not personalized, however—they offer estimates based on groups of people. By taking into account a person’s family history, medical history, and other factors, a genetics professional can help interpret what statistics mean for a particular patient. Common Statistical Terms Some statistical terms are commonly used when describing genetic conditions and other disorders. These terms include: Statistical Term Incidence
Description The incidence of a gene mutation or a genetic disorder is the number of people who are born with the mutation or disorder in a specified group per year. Incidence is often written in the form “1 in [a number]” or as a total number of live births.
Examples About 1 in 200,000 people in the United States are born with syndrome A each year. An estimated 15,000 infants with syndrome B were born last year worldwide.
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Prevalence
The prevalence of a gene mutation or a genetic disorder is the total number of people in a specified group at a given time who have the mutation or disorder. This term includes both newly diagnosed and preexisting cases in people of any age. Prevalence is often written in the form “1 in [a number]” or as a total number of people who have a condition.
Approximately 1 in 100,000 people in the United States have syndrome A at the present time. About 100,000 children worldwide currently have syndrome B.
Mortality
Mortality is the number of deaths from a particular disorder occurring in a specified group per year. Mortality is usually expressed as a total number of deaths.
An estimated 12,000 people worldwide died from syndrome C in 2002.
Lifetime risk
Lifetime risk is the average risk of developing a particular disorder at some point during a lifetime. Lifetime risk is often written as a percentage or as “1 in [a number].” It is important to remember that the risk per year or per decade is much lower than the lifetime risk. In addition, other factors may increase or decrease a person’s risk as compared with the average.
Approximately 1 percent of people in the United States develop disorder D during their lifetimes. The lifetime risk of developing disorder D is 1 in 100.
Naming Genetic Conditions Genetic conditions are not named in one standard way (unlike genes, which are given an official name and symbol by a formal committee). Doctors who treat families with a particular disorder are often the first to propose a name for the condition. Expert working groups may later revise the name to improve its usefulness. Naming is important because it allows accurate and effective communication about particular conditions, which will ultimately help researchers find new approaches to treatment. Disorder names are often derived from one or a combination of sources: •
The basic genetic or biochemical defect that causes the condition (for example, alpha-1 antitrypsin deficiency)
•
One or more major signs or symptoms of the disorder (for example, sickle cell anemia)
•
The parts of the body affected by the condition (for example, retinoblastoma)
•
The name of a physician or researcher, often the first person to describe the disorder (for example, Marfan syndrome, which was named after Dr. Antoine Bernard-Jean Marfan)
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A geographic area (for example, familial Mediterranean fever, which occurs mainly in populations bordering the Mediterranean Sea)
•
The name of a patient or family with the condition (for example, amyotrophic lateral sclerosis, which is also called Lou Gehrig disease after a famous baseball player who had the condition).
Disorders named after a specific person or place are called eponyms. There is debate as to whether the possessive form (e.g., Alzheimer’s disease) or the nonpossessive form (Alzheimer disease) of eponyms is preferred. As a rule, medical geneticists use the nonpossessive form, and this form may become the standard for doctors in all fields of medicine. Genetics Home Reference uses the nonpossessive form of eponyms. Genetics Home Reference consults with experts in the field of medical genetics to provide the current, most accurate name for each disorder. Alternate names are included as synonyms. Naming genes The HUGO Gene Nomenclature Committee (HGNC) designates an official name and symbol (an abbreviation of the name) for each known human gene. Some official gene names include additional information in parentheses, such as related genetic conditions, subtypes of a condition, or inheritance pattern. The HGNC is a non-profit organization funded by the U.K. Medical Research Council and the U.S. National Institutes of Health. The Committee has named more than 13,000 of the estimated 20,000 to 25,000 genes in the human genome. During the research process, genes often acquire several alternate names and symbols. Different researchers investigating the same gene may each give the gene a different name, which can cause confusion. The HGNC assigns a unique name and symbol to each human gene, which allows effective organization of genes in large databanks, aiding the advancement of research. For specific information about how genes are named, refer to the HGNC’s Guidelines for Human Gene Nomenclature. Genetics Home Reference describes genes using the HGNC’s official gene names and gene symbols. Genetics Home Reference frequently presents the symbol and name separated with a colon (for example, FGFR4: Fibroblast growth factor receptor 4).
Inheriting Genetic Conditions This section gives you information on inheritance patterns and understanding risk. What Does It Mean If a Disorder Seems to Run in My Family? A particular disorder might be described as “running in a family” if more than one person in the family has the condition. Some disorders that affect multiple family members are caused by gene mutations, which can be inherited (passed down from parent to child). Other conditions that appear to run in families are not inherited. Instead, environmental factors such as dietary habits or a combination of genetic and environmental factors are responsible for these disorders.
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It is not always easy to determine whether a condition in a family is inherited. A genetics professional can use a person’s family history (a record of health information about a person’s immediate and extended family) to help determine whether a disorder has a genetic component.
Some disorders are seen in more than one generation of a family. Why Is It Important to Know My Family Medical History? A family medical history is a record of health information about a person and his or her close relatives. A complete record includes information from three generations of relatives, including children, brothers and sisters, parents, aunts and uncles, nieces and nephews, grandparents, and cousins.
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Families have many factors in common, including their genes, environment, and lifestyle. Together, these factors can give clues to medical conditions that may run in a family. By noticing patterns of disorders among relatives, healthcare professionals can determine whether an individual, other family members, or future generations may be at an increased risk of developing a particular condition. A family medical history can identify people with a higher-than-usual chance of having common disorders, such as heart disease, high blood pressure, stroke, certain cancers, and diabetes. These complex disorders are influenced by a combination of genetic factors, environmental conditions, and lifestyle choices. A family history also can provide information about the risk of rarer conditions caused by mutations in a single gene, such as cystic fibrosis and sickle cell anemia. While a family medical history provides information about the risk of specific health concerns, having relatives with a medical condition does not mean that an individual will definitely develop that condition. On the other hand, a person with no family history of a disorder may still be at risk of developing that disorder. Knowing one’s family medical history allows a person to take steps to reduce his or her risk. For people at an increased risk of certain cancers, healthcare professionals may recommend more frequent screening (such as mammography or colonoscopy) starting at an earlier age. Healthcare providers may also encourage regular checkups or testing for people with a medical condition that runs in their family. Additionally, lifestyle changes such as adopting a healthier diet, getting regular exercise, and quitting smoking help many people lower their chances of developing heart disease and other common illnesses. The easiest way to get information about family medical history is to talk to relatives about their health. Have they had any medical problems, and when did they occur? A family gathering could be a good time to discuss these issues. Additionally, obtaining medical records and other documents (such as obituaries and death certificates) can help complete a family medical history. It is important to keep this information up-to-date and to share it with a healthcare professional regularly. What Are the Different Ways in which a Genetic Condition Can Be Inherited? Some genetic conditions are caused by mutations in a single gene. These conditions are usually inherited in one of several straightforward patterns, depending on the gene involved: Inheritance Pattern Autosomal dominant
Description One mutated copy of the gene in each cell is sufficient for a person to be affected by an autosomal dominant disorder. Each affected person usually has one affected parent. Autosomal dominant disorders tend to occur in every generation of an affected family.
Examples Huntington disease, neurofibromatosis type 1
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Autosomal recessive
Two mutated copies of the gene are present in each cell when a person has an autosomal recessive disorder. An affected person usually has unaffected parents who each carry a single copy of the mutated gene (and are referred to as carriers). Autosomal recessive disorders are typically not seen in every generation of an affected family.
cystic fibrosis, sickle cell anemia
X-linked dominant
X-linked dominant disorders are caused by mutations in genes on the X chromosome. Females are more frequently affected than males, and the chance of passing on an X-linked dominant disorder differs between men and women. Families with an X-linked dominant disorder often have both affected males and affected females in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).
fragile X syndrome
X-linked recessive
X-linked recessive disorders are also caused by mutations in genes on the X chromosome. Males are more frequently affected than females, and the chance of passing on the disorder differs between men and women. Families with an X-linked recessive disorder often have affected males, but rarely affected females, in each generation. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons (no male-to-male transmission).
hemophilia, Fabry disease
Codominant
In codominant inheritance, two different versions (alleles) of a gene can be expressed, and each version makes a slightly different protein. Both alleles influence the genetic trait or determine the characteristics of the genetic condition.
ABO blood group, alpha-1 antitrypsin deficiency
Mitochondrial
This type of inheritance, also known as maternal inheritance, applies to genes in mitochondrial DNA. Mitochondria, which are structures in each cell that convert molecules into energy, each contain a small amount of DNA. Because only egg cells contribute mitochondria to the developing embryo, only females can pass on mitochondrial conditions to their children. Mitochondrial disorders can appear in every generation of a family and can affect both males and females, but fathers do not pass mitochondrial traits to their children.
Leber hereditary optic neuropathy (LHON)
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Many other disorders are caused by a combination of the effects of multiple genes or by interactions between genes and the environment. Such disorders are more difficult to analyze because their genetic causes are often unclear, and they do not follow the patterns of inheritance described above. Examples of conditions caused by multiple genes or gene/environment interactions include heart disease, diabetes, schizophrenia, and certain types of cancer. Disorders caused by changes in the number or structure of chromosomes do not follow the straightforward patterns of inheritance listed above. Other genetic factors can also influence how a disorder is inherited. If a Genetic Disorder Runs in My Family, What Are the Chances That My Children Will Have the Condition? When a genetic disorder is diagnosed in a family, family members often want to know the likelihood that they or their children will develop the condition. This can be difficult to predict in some cases because many factors influence a person’s chances of developing a genetic condition. One important factor is how the condition is inherited. For example: •
Autosomal dominant inheritance: A person affected by an autosomal dominant disorder has a 50 percent chance of passing the mutated gene to each child. The chance that a child will not inherit the mutated gene is also 50 percent.
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Autosomal recessive inheritance: Two unaffected people who each carry one copy of the mutated gene for an autosomal recessive disorder (carriers) have a 25 percent chance with each pregnancy of having a child affected by the disorder. The chance with each pregnancy of having an unaffected child who is a carrier of the disorder is 50 percent, and the chance that a child will not have the disorder and will not be a carrier is 25 percent.
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X-linked dominant inheritance: The chance of passing on an X-linked dominant condition differs between men and women because men have one X chromosome and one Y chromosome, while women have two X chromosomes. A man passes on his Y chromosome to all of his sons and his X chromosome to all of his daughters. Therefore, the sons of a man with an X-linked dominant disorder will not be affected, but all of his daughters will inherit the condition. A woman passes on one or the other of her X chromosomes to each child. Therefore, a woman with an X-linked dominant disorder has a 50 percent chance of having an affected daughter or son with each pregnancy.
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X-linked recessive inheritance: Because of the difference in sex chromosomes, the probability of passing on an X-linked recessive disorder also differs between men and women. The sons of a man with an X-linked recessive disorder will not be affected, and his daughters will carry one copy of the mutated gene. With each pregnancy, a woman who carries an X-linked recessive disorder has a 50 percent chance of having sons who are affected and a 50 percent chance of having daughters who carry one copy of the mutated gene.
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Codominant inheritance: In codominant inheritance, each parent contributes a different version of a particular gene, and both versions influence the resulting genetic trait. The chance of developing a genetic condition with codominant inheritance, and the characteristic features of that condition, depend on which versions of the gene are passed from parents to their child.
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Mitochondrial inheritance: Mitochondria, which are the energy-producing centers inside cells, each contain a small amount of DNA. Disorders with mitochondrial inheritance result from mutations in mitochondrial DNA. Although mitochondrial
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disorders can affect both males and females, only females can pass mutations in mitochondrial DNA to their children. A woman with a disorder caused by changes in mitochondrial DNA will pass the mutation to all of her daughters and sons, but the children of a man with such a disorder will not inherit the mutation. It is important to note that the chance of passing on a genetic condition applies equally to each pregnancy. For example, if a couple has a child with an autosomal recessive disorder, the chance of having another child with the disorder is still 25 percent (or 1 in 4). Having one child with a disorder does not “protect” future children from inheriting the condition. Conversely, having a child without the condition does not mean that future children will definitely be affected. Although the chances of inheriting a genetic condition appear straightforward, factors such as a person’s family history and the results of genetic testing can sometimes modify those chances. In addition, some people with a disease-causing mutation never develop any health problems or may experience only mild symptoms of the disorder. If a disease that runs in a family does not have a clear-cut inheritance pattern, predicting the likelihood that a person will develop the condition can be particularly difficult. Estimating the chance of developing or passing on a genetic disorder can be complex. Genetics professionals can help people understand these chances and help them make informed decisions about their health. Factors that Influence the Effects of Particular Genetic Changes Reduced penetrance and variable expressivity are factors that influence the effects of particular genetic changes. These factors usually affect disorders that have an autosomal dominant pattern of inheritance, although they are occasionally seen in disorders with an autosomal recessive inheritance pattern. Reduced Penetrance Penetrance refers to the proportion of people with a particular genetic change (such as a mutation in a specific gene) who exhibit signs and symptoms of a genetic disorder. If some people with the mutation do not develop features of the disorder, the condition is said to have reduced (or incomplete) penetrance. Reduced penetrance often occurs with familial cancer syndromes. For example, many people with a mutation in the BRCA1 or BRCA2 gene will develop cancer during their lifetime, but some people will not. Doctors cannot predict which people with these mutations will develop cancer or when the tumors will develop. Reduced penetrance probably results from a combination of genetic, environmental, and lifestyle factors, many of which are unknown. This phenomenon can make it challenging for genetics professionals to interpret a person’s family medical history and predict the risk of passing a genetic condition to future generations. Variable Expressivity Although some genetic disorders exhibit little variation, most have signs and symptoms that differ among affected individuals. Variable expressivity refers to the range of signs and
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symptoms that can occur in different people with the same genetic condition. For example, the features of Marfan syndrome vary widely— some people have only mild symptoms (such as being tall and thin with long, slender fingers), while others also experience lifethreatening complications involving the heart and blood vessels. Although the features are highly variable, most people with this disorder have a mutation in the same gene (FBN1). As with reduced penetrance, variable expressivity is probably caused by a combination of genetic, environmental, and lifestyle factors, most of which have not been identified. If a genetic condition has highly variable signs and symptoms, it may be challenging to diagnose. What Do Geneticists Mean by Anticipation? The signs and symptoms of some genetic conditions tend to become more severe and appear at an earlier age as the disorder is passed from one generation to the next. This phenomenon is called anticipation. Anticipation is most often seen with certain genetic disorders of the nervous system, such as Huntington disease, myotonic dystrophy, and fragile X syndrome. Anticipation typically occurs with disorders that are caused by an unusual type of mutation called a trinucleotide repeat expansion. A trinucleotide repeat is a sequence of three DNA building blocks (nucleotides) that is repeated a number of times in a row. DNA segments with an abnormal number of these repeats are unstable and prone to errors during cell division. The number of repeats can change as the gene is passed from parent to child. If the number of repeats increases, it is known as a trinucleotide repeat expansion. In some cases, the trinucleotide repeat may expand until the gene stops functioning normally. This expansion causes the features of some disorders to become more severe with each successive generation. Most genetic disorders have signs and symptoms that differ among affected individuals, including affected people in the same family. Not all of these differences can be explained by anticipation. A combination of genetic, environmental, and lifestyle factors is probably responsible for the variability, although many of these factors have not been identified. Researchers study multiple generations of affected family members and consider the genetic cause of a disorder before determining that it shows anticipation. What Is Genomic Imprinting? Genomic imprinting is a factor that influences how some genetic conditions are inherited. People inherit two copies of their genes—one from their mother and one from their father. Usually both copies of each gene are active, or “turned on,” in cells. In some cases, however, only one of the two copies is normally turned on. Which copy is active depends on the parent of origin: some genes are normally active only when they are inherited from a person’s father; others are active only when inherited from a person’s mother. This phenomenon is known as genomic imprinting. In genes that undergo genomic imprinting, the parent of origin is often marked, or “stamped,” on the gene during the formation of egg and sperm cells. This stamping process, called methylation, is a chemical reaction that attaches small molecules called methyl groups to certain segments of DNA. These molecules identify which copy of a gene was inherited
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from the mother and which was inherited from the father. The addition and removal of methyl groups can be used to control the activity of genes. Only a small percentage of all human genes undergo genomic imprinting. Researchers are not yet certain why some genes are imprinted and others are not. They do know that imprinted genes tend to cluster together in the same regions of chromosomes. Two major clusters of imprinted genes have been identified in humans, one on the short (p) arm of chromosome 11 (at position 11p15) and another on the long (q) arm of chromosome 15 (in the region 15q11 to 15q13). What Is Uniparental Disomy? Uniparental disomy is a factor that influences how some genetic conditions are inherited. Uniparental disomy (UPD) occurs when a person receives two copies of a chromosome, or part of a chromosome, from one parent and no copies from the other parent. UPD can occur as a random event during the formation of egg or sperm cells or may happen in early fetal development. In many cases, UPD likely has no effect on health or development. Because most genes are not imprinted, it doesn’t matter if a person inherits both copies from one parent instead of one copy from each parent. In some cases, however, it does make a difference whether a gene is inherited from a person’s mother or father. A person with UPD may lack any active copies of essential genes that undergo genomic imprinting. This loss of gene function can lead to delayed development, mental retardation, or other medical problems. Several genetic disorders can result from UPD or a disruption of normal genomic imprinting. The most well-known conditions include Prader-Willi syndrome, which is characterized by uncontrolled eating and obesity, and Angelman syndrome, which causes mental retardation and impaired speech. Both of these disorders can be caused by UPD or other errors in imprinting involving genes on the long arm of chromosome 15. Other conditions, such as Beckwith-Wiedemann syndrome (a disorder characterized by accelerated growth and an increased risk of cancerous tumors), are associated with abnormalities of imprinted genes on the short arm of chromosome 11. Are Chromosomal Disorders Inherited? Although it is possible to inherit some types of chromosomal abnormalities, most chromosomal disorders (such as Down syndrome and Turner syndrome) are not passed from one generation to the next. Some chromosomal conditions are caused by changes in the number of chromosomes. These changes are not inherited, but occur as random events during the formation of reproductive cells (eggs and sperm). An error in cell division called nondisjunction results in reproductive cells with an abnormal number of chromosomes. For example, a reproductive cell may accidentally gain or lose one copy of a chromosome. If one of these atypical reproductive cells contributes to the genetic makeup of a child, the child will have an extra or missing chromosome in each of the body’s cells.
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Changes in chromosome structure can also cause chromosomal disorders. Some changes in chromosome structure can be inherited, while others occur as random accidents during the formation of reproductive cells or in early fetal development. Because the inheritance of these changes can be complex, people concerned about this type of chromosomal abnormality may want to talk with a genetics professional. Some cancer cells also have changes in the number or structure of their chromosomes. Because these changes occur in somatic cells (cells other than eggs and sperm), they cannot be passed from one generation to the next. Why Are Some Genetic Conditions More Common in Particular Ethnic Groups? Some genetic disorders are more likely to occur among people who trace their ancestry to a particular geographic area. People in an ethnic group often share certain versions of their genes, which have been passed down from common ancestors. If one of these shared genes contains a disease-causing mutation, a particular genetic disorder may be more frequently seen in the group. Examples of genetic conditions that are more common in particular ethnic groups are sickle cell anemia, which is more common in people of African, African-American, or Mediterranean heritage; and Tay-Sachs disease, which is more likely to occur among people of Ashkenazi (eastern and central European) Jewish or French Canadian ancestry. It is important to note, however, that these disorders can occur in any ethnic group.
Genetic Consultation This section presents information on finding and visiting a genetic counselor or other genetics professional. What Is a Genetic Consultation? A genetic consultation is a health service that provides information and support to people who have, or may be at risk for, genetic disorders. During a consultation, a genetics professional meets with an individual or family to discuss genetic risks or to diagnose, confirm, or rule out a genetic condition. Genetics professionals include medical geneticists (doctors who specialize in genetics) and genetic counselors (certified healthcare workers with experience in medical genetics and counseling). Other healthcare professionals such as nurses, psychologists, and social workers trained in genetics can also provide genetic consultations. Consultations usually take place in a doctor’s office, hospital, genetics center, or other type of medical center. These meetings are most often in-person visits with individuals or families, but they are occasionally conducted in a group or over the telephone.
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Why Might Someone Have a Genetic Consultation? Individuals or families who are concerned about an inherited condition may benefit from a genetic consultation. The reasons that a person might be referred to a genetic counselor, medical geneticist, or other genetics professional include: •
A personal or family history of a genetic condition, birth defect, chromosomal disorder, or hereditary cancer.
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Two or more pregnancy losses (miscarriages), a stillbirth, or a baby who died.
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A child with a known inherited disorder, a birth defect, mental retardation, or developmental delay.
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A woman who is pregnant or plans to become pregnant at or after age 35. (Some chromosomal disorders occur more frequently in children born to older women.)
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Abnormal test results that suggest a genetic or chromosomal condition.
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An increased risk of developing or passing on a particular genetic disorder on the basis of a person’s ethnic background.
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People related by blood (for example, cousins) who plan to have children together. (A child whose parents are related may be at an increased risk of inheriting certain genetic disorders.)
A genetic consultation is also an important part of the decision-making process for genetic testing. A visit with a genetics professional may be helpful even if testing is not available for a specific condition, however. What Happens during a Genetic Consultation? A genetic consultation provides information, offers support, and addresses a patient’s specific questions and concerns. To help determine whether a condition has a genetic component, a genetics professional asks about a person’s medical history and takes a detailed family history (a record of health information about a person’s immediate and extended family). The genetics professional may also perform a physical examination and recommend appropriate tests. If a person is diagnosed with a genetic condition, the genetics professional provides information about the diagnosis, how the condition is inherited, the chance of passing the condition to future generations, and the options for testing and treatment. During a consultation, a genetics professional will: •
Interpret and communicate complex medical information.
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Help each person make informed, independent decisions about their health care and reproductive options.
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Respect each person’s individual beliefs, traditions, and feelings.
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Tell a person which decision to make.
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Advise a couple not to have children.
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Recommend that a woman continue or end a pregnancy.
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Tell someone whether to undergo testing for a genetic disorder.
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How Can I Find a Genetics Professional in My Area? To find a genetics professional in your community, you may wish to ask your doctor for a referral. If you have health insurance, you can also contact your insurance company to find a medical geneticist or genetic counselor in your area who participates in your plan. Several resources for locating a genetics professional in your community are available online: •
GeneTests from the University of Washington provides a list of genetics clinics around the United States and international genetics clinics. You can also access the list by clicking on “Clinic Directory” at the top of the GeneTests home page. Clinics can be chosen by state or country, by service, and/or by specialty. State maps can help you locate a clinic in your area. See http://www.genetests.org/.
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The National Society of Genetic Counselors offers a searchable directory of genetic counselors in the United States. You can search by location, name, area of practice/specialization, and/or ZIP Code. See http://www.nsgc.org/resourcelink.cfm.
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The National Cancer Institute provides a Cancer Genetics Services Directory, which lists professionals who provide services related to cancer genetics. You can search by type of cancer or syndrome, location, and/or provider name at the following Web site: http://cancer.gov/search/genetics_services/.
Genetic Testing This section presents information on the benefits, costs, risks, and limitations of genetic testing. What Is Genetic Testing? Genetic testing is a type of medical test that identifies changes in chromosomes, genes, or proteins. Most of the time, testing is used to find changes that are associated with inherited disorders. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing or passing on a genetic disorder. Several hundred genetic tests are currently in use, and more are being developed. Genetic testing is voluntary. Because testing has both benefits and limitations, the decision about whether to be tested is a personal and complex one. A genetic counselor can help by providing information about the pros and cons of the test and discussing the social and emotional aspects of testing.
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What Are the Types of Genetic Tests? Genetic testing can provide information about a person’s genes and chromosomes. Available types of testing include: •
Newborn screening is used just after birth to identify genetic disorders that can be treated early in life. Millions of babies are tested each year in the United States. All states currently test infants for phenylketonuria (a genetic disorder that causes mental retardation if left untreated) and congenital hypothyroidism (a disorder of the thyroid gland). Most states also test for other genetic disorders.
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Diagnostic testing is used to identify or rule out a specific genetic or chromosomal condition. In many cases, genetic testing is used to confirm a diagnosis when a particular condition is suspected based on physical signs and symptoms. Diagnostic testing can be performed before birth or at any time during a person’s life, but is not available for all genes or all genetic conditions. The results of a diagnostic test can influence a person’s choices about health care and the management of the disorder.
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Carrier testing is used to identify people who carry one copy of a gene mutation that, when present in two copies, causes a genetic disorder. This type of testing is offered to individuals who have a family history of a genetic disorder and to people in certain ethnic groups with an increased risk of specific genetic conditions. If both parents are tested, the test can provide information about a couple’s risk of having a child with a genetic condition.
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Prenatal testing is used to detect changes in a fetus’s genes or chromosomes before birth. This type of testing is offered during pregnancy if there is an increased risk that the baby will have a genetic or chromosomal disorder. In some cases, prenatal testing can lessen a couple’s uncertainty or help them make decisions about a pregnancy. It cannot identify all possible inherited disorders and birth defects, however.
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Preimplantation testing, also called preimplantation genetic diagnosis (PGD), is a specialized technique that can reduce the risk of having a child with a particular genetic or chromosomal disorder. It is used to detect genetic changes in embryos that were created using assisted reproductive techniques such as in-vitro fertilization. In-vitro fertilization involves removing egg cells from a woman’s ovaries and fertilizing them with sperm cells outside the body. To perform preimplantation testing, a small number of cells are taken from these embryos and tested for certain genetic changes. Only embryos without these changes are implanted in the uterus to initiate a pregnancy.
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Predictive and presymptomatic types of testing are used to detect gene mutations associated with disorders that appear after birth, often later in life. These tests can be helpful to people who have a family member with a genetic disorder, but who have no features of the disorder themselves at the time of testing. Predictive testing can identify mutations that increase a person’s risk of developing disorders with a genetic basis, such as certain types of cancer. Presymptomatic testing can determine whether a person will develop a genetic disorder, such as hemochromatosis (an iron overload disorder), before any signs or symptoms appear. The results of predictive and presymptomatic testing can provide information about a person’s risk of developing a specific disorder and help with making decisions about medical care.
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Forensic testing uses DNA sequences to identify an individual for legal purposes. Unlike the tests described above, forensic testing is not used to detect gene mutations associated with disease. This type of testing can identify crime or catastrophe victims, rule out or implicate a crime suspect, or establish biological relationships between people (for example, paternity).
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How Is Genetic Testing Done? Once a person decides to proceed with genetic testing, a medical geneticist, primary care doctor, specialist, or nurse practitioner can order the test. Genetic testing is often done as part of a genetic consultation. Genetic tests are performed on a sample of blood, hair, skin, amniotic fluid (the fluid that surrounds a fetus during pregnancy), or other tissue. For example, a procedure called a buccal smear uses a small brush or cotton swab to collect a sample of cells from the inside surface of the cheek. The sample is sent to a laboratory where technicians look for specific changes in chromosomes, DNA, or proteins, depending on the suspected disorder. The laboratory reports the test results in writing to a person’s doctor or genetic counselor. Newborn screening tests are done on a small blood sample, which is taken by pricking the baby’s heel. Unlike other types of genetic testing, a parent will usually only receive the result if it is positive. If the test result is positive, additional testing is needed to determine whether the baby has a genetic disorder. Before a person has a genetic test, it is important that he or she understands the testing procedure, the benefits and limitations of the test, and the possible consequences of the test results. The process of educating a person about the test and obtaining permission is called informed consent. What Is Direct-to-Consumer Genetic Testing? Traditionally, genetic tests have been available only through healthcare providers such as physicians, nurse practitioners, and genetic counselors. Healthcare providers order the appropriate test from a laboratory, collect and send the samples, and interpret the test results. Direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print advertisements, or the Internet. This form of testing, which is also known as at-home genetic testing, provides access to a person’s genetic information without necessarily involving a doctor or insurance company in the process. If a consumer chooses to purchase a genetic test directly, the test kit is mailed to the consumer instead of being ordered through a doctor’s office. The test typically involves collecting a DNA sample at home, often by swabbing the inside of the cheek, and mailing the sample back to the laboratory. In some cases, the person must visit a health clinic to have blood drawn. Consumers are notified of their results by mail or over the telephone, or the results are posted online. In some cases, a genetic counselor or other healthcare provider is available to explain the results and answer questions. The price for this type of at-home genetic testing ranges from several hundred dollars to more than a thousand dollars. The growing market for direct-to-consumer genetic testing may promote awareness of genetic diseases, allow consumers to take a more proactive role in their health care, and offer a means for people to learn about their ancestral origins. At-home genetic tests, however, have significant risks and limitations. Consumers are vulnerable to being misled by the results of unproven or invalid tests. Without guidance from a healthcare provider, they may make important decisions about treatment or prevention based on inaccurate, incomplete, or misunderstood information about their health. Consumers may also experience an invasion of genetic privacy if testing companies use their genetic information in an unauthorized way.
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Genetic testing provides only one piece of information about a person’s health—other genetic and environmental factors, lifestyle choices, and family medical history also affect a person’s risk of developing many disorders. These factors are discussed during a consultation with a doctor or genetic counselor, but in many cases are not addressed by athome genetic tests. More research is needed to fully understand the benefits and limitations of direct-to-consumer genetic testing. What Do the Results of Genetic Tests Mean? The results of genetic tests are not always straightforward, which often makes them challenging to interpret and explain. Therefore, it is important for patients and their families to ask questions about the potential meaning of genetic test results both before and after the test is performed. When interpreting test results, healthcare professionals consider a person’s medical history, family history, and the type of genetic test that was done. A positive test result means that the laboratory found a change in a particular gene, chromosome, or protein of interest. Depending on the purpose of the test, this result may confirm a diagnosis, indicate that a person is a carrier of a particular genetic mutation, identify an increased risk of developing a disease (such as cancer) in the future, or suggest a need for further testing. Because family members have some genetic material in common, a positive test result may also have implications for certain blood relatives of the person undergoing testing. It is important to note that a positive result of a predictive or presymptomatic genetic test usually cannot establish the exact risk of developing a disorder. Also, health professionals typically cannot use a positive test result to predict the course or severity of a condition. A negative test result means that the laboratory did not find a change in the gene, chromosome, or protein under consideration. This result can indicate that a person is not affected by a particular disorder, is not a carrier of a specific genetic mutation, or does not have an increased risk of developing a certain disease. It is possible, however, that the test missed a disease-causing genetic alteration because many tests cannot detect all genetic changes that can cause a particular disorder. Further testing may be required to confirm a negative result. In some cases, a negative result might not give any useful information. This type of result is called uninformative, indeterminate, inconclusive, or ambiguous. Uninformative test results sometimes occur because everyone has common, natural variations in their DNA, called polymorphisms, that do not affect health. If a genetic test finds a change in DNA that has not been associated with a disorder in other people, it can be difficult to tell whether it is a natural polymorphism or a disease-causing mutation. An uninformative result cannot confirm or rule out a specific diagnosis, and it cannot indicate whether a person has an increased risk of developing a disorder. In some cases, testing other affected and unaffected family members can help clarify this type of result. What Is the Cost of Genetic Testing, and How Long Does It Take to Get the Results? The cost of genetic testing can range from under $100 to more than $2,000, depending on the nature and complexity of the test. The cost increases if more than one test is necessary or if multiple family members must be tested to obtain a meaningful result. For newborn
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screening, costs vary by state. Some states cover part of the total cost, but most charge a fee of $15 to $60 per infant. From the date that a sample is taken, it may take a few weeks to several months to receive the test results. Results for prenatal testing are usually available more quickly because time is an important consideration in making decisions about a pregnancy. The doctor or genetic counselor who orders a particular test can provide specific information about the cost and time frame associated with that test. Will Health Insurance Cover the Costs of Genetic Testing? In many cases, health insurance plans will cover the costs of genetic testing when it is recommended by a person’s doctor. Health insurance providers have different policies about which tests are covered, however. A person interested in submitting the costs of testing may wish to contact his or her insurance company beforehand to ask about coverage. Some people may choose not to use their insurance to pay for testing because the results of a genetic test can affect a person’s health insurance coverage. Instead, they may opt to pay out-of-pocket for the test. People considering genetic testing may want to find out more about their state’s privacy protection laws before they ask their insurance company to cover the costs. What Are the Benefits of Genetic Testing? Genetic testing has potential benefits whether the results are positive or negative for a gene mutation. Test results can provide a sense of relief from uncertainty and help people make informed decisions about managing their health care. For example, a negative result can eliminate the need for unnecessary checkups and screening tests in some cases. A positive result can direct a person toward available prevention, monitoring, and treatment options. Some test results can also help people make decisions about having children. Newborn screening can identify genetic disorders early in life so treatment can be started as early as possible. What Are the Risks and Limitations of Genetic Testing? The physical risks associated with most genetic tests are very small, particularly for those tests that require only a blood sample or buccal smear (a procedure that samples cells from the inside surface of the cheek). The procedures used for prenatal testing carry a small but real risk of losing the pregnancy (miscarriage) because they require a sample of amniotic fluid or tissue from around the fetus. Many of the risks associated with genetic testing involve the emotional, social, or financial consequences of the test results. People may feel angry, depressed, anxious, or guilty about their results. In some cases, genetic testing creates tension within a family because the results can reveal information about other family members in addition to the person who is tested. The possibility of genetic discrimination in employment or insurance is also a concern.
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Genetic testing can provide only limited information about an inherited condition. The test often can’t determine if a person will show symptoms of a disorder, how severe the symptoms will be, or whether the disorder will progress over time. Another major limitation is the lack of treatment strategies for many genetic disorders once they are diagnosed. A genetics professional can explain in detail the benefits, risks, and limitations of a particular test. It is important that any person who is considering genetic testing understand and weigh these factors before making a decision. What Is Genetic Discrimination? Genetic discrimination occurs when people are treated differently by their employer or insurance company because they have a gene mutation that causes or increases the risk of an inherited disorder. People who undergo genetic testing may be at risk for genetic discrimination. The results of a genetic test are normally included in a person’s medical records. When a person applies for life, disability, or health insurance, the insurance company may ask to look at these records before making a decision about coverage. An employer may also have the right to look at an employee’s medical records. As a result, genetic test results could affect a person’s insurance coverage or employment. People making decisions about genetic testing should be aware that when test results are placed in their medical records, the results might not be kept private. Fear of discrimination is a common concern among people considering genetic testing. Several laws at the federal and state levels help protect people against genetic discrimination; however, genetic testing is a fast-growing field and these laws don’t cover every situation. How Does Genetic Testing in a Research Setting Differ from Clinical Genetic Testing? The main differences between clinical genetic testing and research testing are the purpose of the test and who receives the results. The goals of research testing include finding unknown genes, learning how genes work, and advancing our understanding of genetic conditions. The results of testing done as part of a research study are usually not available to patients or their healthcare providers. Clinical testing, on the other hand, is done to find out about an inherited disorder in an individual patient or family. People receive the results of a clinical test and can use them to help them make decisions about medical care or reproductive issues. It is important for people considering genetic testing to know whether the test is available on a clinical or research basis. Clinical and research testing both involve a process of informed consent in which patients learn about the testing procedure, the risks and benefits of the test, and the potential consequences of testing.
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Gene Therapy This section presents information on experimental techniques, safety, ethics, and availability of gene therapy. What Is Gene Therapy? Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including: •
Replacing a mutated gene that causes disease with a healthy copy of the gene.
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Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
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Introducing a new gene into the body to help fight a disease.
Although gene therapy is a promising treatment option for a number of diseases (including inherited disorders, some types of cancer, and certain viral infections), the technique remains risky and is still under study to make sure that it will be safe and effective. Gene therapy is currently only being tested for the treatment of diseases that have no other cures. How Does Gene Therapy Work? Gene therapy is designed to introduce genetic material into cells to compensate for abnormal genes or to make a beneficial protein. If a mutated gene causes a necessary protein to be faulty or missing, gene therapy may be able to introduce a normal copy of the gene to restore the function of the protein. A gene that is inserted directly into a cell usually does not function. Instead, a carrier called a vector is genetically engineered to deliver the gene. Certain viruses are often used as vectors because they can deliver the new gene by infecting the cell. The viruses are modified so they can’t cause disease when used in people. Some types of virus, such as retroviruses, integrate their genetic material (including the new gene) into a chromosome in the human cell. Other viruses, such as adenoviruses, introduce their DNA into the nucleus of the cell, but the DNA is not integrated into a chromosome. The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient’s cells can be removed and exposed to the vector in a laboratory setting. The cells containing the vector are then returned to the patient. If the treatment is successful, the new gene delivered by the vector will make a functioning protein. Researchers must overcome many technical challenges before gene therapy will be a practical approach to treating disease. For example, scientists must find better ways to deliver genes and target them to particular cells. They must also ensure that new genes are precisely controlled by the body.
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A new gene is injected into an adenovirus vector, which is used to introduce the modified DNA into a human cell. If the treatment is successful, the new gene will make a functional protein.
Is Gene Therapy Safe? Gene therapy is under study to determine whether it could be used to treat disease. Current research is evaluating the safety of gene therapy; future studies will test whether it is an effective treatment option. Several studies have already shown that this approach can have very serious health risks, such as toxicity, inflammation, and cancer. Because the techniques are relatively new, some of the risks may be unpredictable; however, medical researchers, institutions, and regulatory agencies are working to ensure that gene therapy research is as safe as possible. Comprehensive federal laws, regulations, and guidelines help protect people who participate in research studies (called clinical trials). The U.S. Food and Drug Administration (FDA) regulates all gene therapy products in the United States and oversees research in this area. Researchers who wish to test an approach in a clinical trial must first obtain permission from the FDA. The FDA has the authority to reject or suspend clinical trials that are suspected of being unsafe for participants. The National Institutes of Health (NIH) also plays an important role in ensuring the safety of gene therapy research. NIH provides guidelines for investigators and institutions (such as universities and hospitals) to follow when conducting clinical trials with gene therapy. These guidelines state that clinical trials at institutions receiving NIH funding for this type of research must be registered with the NIH Office of Biotechnology Activities. The protocol, or plan, for each clinical trial is then reviewed by the NIH Recombinant DNA Advisory Committee (RAC) to determine whether it raises medical, ethical, or safety issues that warrant further discussion at one of the RAC’s public meetings.
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An Institutional Review Board (IRB) and an Institutional Biosafety Committee (IBC) must approve each gene therapy clinical trial before it can be carried out. An IRB is a committee of scientific and medical advisors and consumers that reviews all research within an institution. An IBC is a group that reviews and approves an institution’s potentially hazardous research studies. Multiple levels of evaluation and oversight ensure that safety concerns are a top priority in the planning and carrying out of gene therapy research. What Are the Ethical Issues surrounding Gene Therapy? Because gene therapy involves making changes to the body’s set of basic instructions, it raises many unique ethical concerns. The ethical questions surrounding gene therapy include: •
How can “good” and “bad” uses of gene therapy be distinguished?
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Who decides which traits are normal and which constitute a disability or disorder?
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Will the high costs of gene therapy make it available only to the wealthy?
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Could the widespread use of gene therapy make society less accepting of people who are different?
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Should people be allowed to use gene therapy to enhance basic human traits such as height, intelligence, or athletic ability?
Current gene therapy research has focused on treating individuals by targeting the therapy to body cells such as bone marrow or blood cells. This type of gene therapy cannot be passed on to a person’s children. Gene therapy could be targeted to egg and sperm cells (germ cells), however, which would allow the inserted gene to be passed on to future generations. This approach is known as germline gene therapy. The idea of germline gene therapy is controversial. While it could spare future generations in a family from having a particular genetic disorder, it might affect the development of a fetus in unexpected ways or have long-term side effects that are not yet known. Because people who would be affected by germline gene therapy are not yet born, they can’t choose whether to have the treatment. Because of these ethical concerns, the U.S. Government does not allow federal funds to be used for research on germline gene therapy in people. Is Gene Therapy Available to Treat My Disorder? Gene therapy is currently available only in a research setting. The U.S. Food and Drug Administration (FDA) has not yet approved any gene therapy products for sale in the United States. Hundreds of research studies (clinical trials) are under way to test gene therapy as a treatment for genetic conditions, cancer, and HIV/AIDS. If you are interested in participating in a clinical trial, talk with your doctor or a genetics professional about how to participate. You can also search for clinical trials online. ClinicalTrials.gov, a service of the National Institutes of Health, provides easy access to information on clinical trials. You can search for
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specific trials or browse by condition or trial sponsor. You may wish to refer to a list of gene therapy trials that are accepting (or will accept) patients.
The Human Genome Project and Genomic Research This section presents information on the goals, accomplishments, and next steps in understanding the human genome. What Is a Genome? A genome is an organism’s complete set of DNA, including all of its genes. Each genome contains all of the information needed to build and maintain that organism. In humans, a copy of the entire genome—more than 3 billion DNA base pairs—is contained in all cells that have a nucleus. What Was the Human Genome Project and Why Has It Been Important? The Human Genome Project was an international research effort to determine the sequence of the human genome and identify the genes that it contains. The Project was coordinated by the National Institutes of Health and the U.S. Department of Energy. Additional contributors included universities across the United States and international partners in the United Kingdom, France, Germany, Japan, and China. The Human Genome Project formally began in 1990 and was completed in 2003, 2 years ahead of its original schedule. The work of the Human Genome Project has allowed researchers to begin to understand the blueprint for building a person. As researchers learn more about the functions of genes and proteins, this knowledge will have a major impact in the fields of medicine, biotechnology, and the life sciences. What Were the Goals of the Human Genome Project? The main goals of the Human Genome Project were to provide a complete and accurate sequence of the 3 billion DNA base pairs that make up the human genome and to find all of the estimated 20,000 to 25,000 human genes. The Project also aimed to sequence the genomes of several other organisms that are important to medical research, such as the mouse and the fruit fly. In addition to sequencing DNA, the Human Genome Project sought to develop new tools to obtain and analyze the data and to make this information widely available. Also, because advances in genetics have consequences for individuals and society, the Human Genome Project committed to exploring the consequences of genomic research through its Ethical, Legal, and Social Implications (ELSI) program. What Did the Human Genome Project Accomplish? In April 2003, researchers announced that the Human Genome Project had completed a high-quality sequence of essentially the entire human genome. This sequence closed the
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gaps from a working draft of the genome, which was published in 2001. It also identified the locations of many human genes and provided information about their structure and organization. The Project made the sequence of the human genome and tools to analyze the data freely available via the Internet. In addition to the human genome, the Human Genome Project sequenced the genomes of several other organisms, including brewers’ yeast, the roundworm, and the fruit fly. In 2002, researchers announced that they had also completed a working draft of the mouse genome. By studying the similarities and differences between human genes and those of other organisms, researchers can discover the functions of particular genes and identify which genes are critical for life. The Project’s Ethical, Legal, and Social Implications (ELSI) program became the world’s largest bioethics program and a model for other ELSI programs worldwide. What Were Some of the Ethical, Legal, and Social Implications Addressed by the Human Genome Project? The Ethical, Legal, and Social Implications (ELSI) program was founded in 1990 as an integral part of the Human Genome Project. The mission of the ELSI program was to identify and address issues raised by genomic research that would affect individuals, families, and society. A percentage of the Human Genome Project budget at the National Institutes of Health and the U.S. Department of Energy was devoted to ELSI research. The ELSI program focused on the possible consequences of genomic research in four main areas: •
Privacy and fairness in the use of genetic information, including the potential for genetic discrimination in employment and insurance.
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The integration of new genetic technologies, such as genetic testing, into the practice of clinical medicine.
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Ethical issues surrounding the design and conduct of genetic research with people, including the process of informed consent.
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The education of healthcare professionals, policy makers, students, and the public about genetics and the complex issues that result from genomic research. What Are the Next Steps in Genomic Research?
Discovering the sequence of the human genome was only the first step in understanding how the instructions coded in DNA lead to a functioning human being. The next stage of genomic research will begin to derive meaningful knowledge from the DNA sequence. Research studies that build on the work of the Human Genome Project are under way worldwide. The objectives of continued genomic research include the following: •
Determine the function of genes and the elements that regulate genes throughout the genome.
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Find variations in the DNA sequence among people and determine their significance. These variations may one day provide information about a person’s disease risk and response to certain medications.
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Discover the 3-dimensional structures of proteins and identify their functions.
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Explore how DNA and proteins interact with one another and with the environment to create complex living systems.
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Develop and apply genome-based strategies for the early detection, diagnosis, and treatment of disease.
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Sequence the genomes of other organisms, such as the rat, cow, and chimpanzee, in order to compare similar genes between species.
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Develop new technologies to study genes and DNA on a large scale and store genomic data efficiently.
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Continue to explore the ethical, legal, and social issues raised by genomic research. What Is Pharmacogenomics?
Pharmacogenomics is the study of how genes affect a person’s response to drugs. This relatively new field combines pharmacology (the science of drugs) and genomics (the study of genes and their functions) to develop effective, safe medications and doses that will be tailored to a person’s genetic makeup. Many drugs that are currently available are “one size fits all,” but they don’t work the same way for everyone. It can be difficult to predict who will benefit from a medication, who will not respond at all, and who will experience negative side effects (called adverse drug reactions). Adverse drug reactions are a significant cause of hospitalizations and deaths in the United States. With the knowledge gained from the Human Genome Project, researchers are learning how inherited differences in genes affect the body’s response to medications. These genetic differences will be used to predict whether a medication will be effective for a particular person and to help prevent adverse drug reactions. The field of pharmacogenomics is still in its infancy. Its use is currently quite limited, but new approaches are under study in clinical trials. In the future, pharmacogenomics will allow the development of tailored drugs to treat a wide range of health problems, including cardiovascular disease, Alzheimer disease, cancer, HIV/AIDS, and asthma.
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APPENDIX B. 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 Institute16: •
National Institutes of Health (NIH); guidelines consolidated across agencies available at http://health.nih.gov/
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/Publications/FactSheets.htm
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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/cancertopics/pdq
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/health/
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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/HealthInformation/Publications/
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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/Publications/
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These publications are typically written by one or more of the various NIH Institutes.
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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.nidcr.nih.gov/HealthInformation/
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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/healthinformation/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 Biomedical Imaging and Bioengineering; general information at http://www.nibib.nih.gov/HealthEdu
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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
NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.17 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
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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).
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citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine18: •
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/index.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
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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
18
See http://www.nlm.nih.gov/databases/index.html.
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The NLM Gateway19 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.20 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type Parkinson disease (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 32878 583 72 33 5 33571
HSTAT21 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.22 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.23 Simply search by Parkinson disease (or synonyms) at the following Web site: http://text.nlm.nih.gov. Coffee Break: Tutorials for Biologists24 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. 19
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
20
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). 21 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 22 23
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. 24 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
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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.25 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.26 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: •
MD Consult: Access to electronic clinical resources, see http://www.mdconsult.com/.
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Medical Matrix: Lists over 6000 medical Web sites and links to over 1.5 million documents with clinical content, see http://www.medmatrix.org/.
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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 Parkinson Disease In the following section, we will discuss databases and references which relate to the Genome Project and Parkinson disease. 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).27 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. To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type Parkinson disease (or synonyms) into the search box, and click Go. If too many results appear, you can narrow the search by adding the word clinical. Each report will have
25
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. 26 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. 27 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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additional links to related research and databases. The following is an example of the results you can obtain from the OMIM for Parkinson disease: •
PARKINSON DISEASE 12 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300557
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PARKINSON DISEASE 2, AUTOSOMAL RECESSIVE JUVENILE; PARK2 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=600116
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PARKINSON DISEASE 3, AUTOSOMAL DOMINANT LEWY BODY; PARK3 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=602404
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PARKINSON DISEASE 4, AUTOSOMAL DOMINANT LEWY BODY; PARK4 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605543
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PARKINSON DISEASE 6, AUTOSOMAL RECESSIVE EARLY-ONSET; PARK6 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=605909
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PARKINSON DISEASE 7, AUTOSOMAL RECESSIVE EARLY-ONSET; PARK7 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606324
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PARKINSON DISEASE 10; PARK10 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606852
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PARKINSON DISEASE 8; PARK8 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607060
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PARKINSON DISEASE 11; PARK11 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=607688
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PARKINSON DISEASE 13; PARK13 Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=610297 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,
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glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html •
Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
•
Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
•
Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
•
Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
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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GEO DataSets: Curated gene expression and molecular abundance data sets assembled from the Gene Expression Omnibus (GEO) repository, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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GEO Profiles: Individual gene expression and molecular abundance profiles assembled from the Gene Expression Omnibus (GEO) repository, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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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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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/gquery/gquery.fcgi, and then select the database that you would like to search. Or, to search across databases, you can enter Parkinson disease (or synonyms) into the search box and click Go. Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database28 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 Database29 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the GDB Human 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 28
Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 29 Adapted from the Genome Database: http://www.gdb.org/gdb/aboutGDB.html#mission.
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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 Name/GDB ID. Type Parkinson disease (or synonyms) into the search box, and review the results. If more than one word is used in the search box, then separate each one with the word and or or (using or might be useful when using synonyms).
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APPENDIX C. 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 Parkinson disease can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internetbased services that post them.
Patient Guideline Sources This section directs you to sources which either publish fact sheets or can help you find additional guidelines on topics related to Parkinson disease. 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 Parkinson disease. 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 Parkinson disease:
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Dementia http://www.nlm.nih.gov/medlineplus/dementia.html Huntington's Disease http://www.nlm.nih.gov/medlineplus/huntingtonsdisease.html Lewy Body Disease http://www.nlm.nih.gov/medlineplus/lewybodydisease.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 National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword Parkinson disease (or synonyms). The following was recently posted: •
Practice parameter: diagnosis and prognosis of new onset Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2006; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=9121&nbr=004935& amp;string=Parkinson+AND+disease
•
Practice parameter: evaluation and treatment of depression, psychosis, and dementia in Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2006; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=9123&nbr=004937& amp;string=Parkinson+AND+disease
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Practice parameter: neuroprotective strategies and alternative therapies for Parkinson disease (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2006; 7 pages http://www.guideline.gov/summary/summary.aspx?doc_id=9122&nbr=004936& amp;string=Parkinson+AND+disease
•
Practice parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology Source: American Academy of Neurology - Medical Specialty Society; 2006; 13 pages http://www.guideline.gov/summary/summary.aspx?doc_id=9124&nbr=004938& amp;string=Parkinson+AND+disease Healthfinder™
Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •
Parkinson's Disease: Hope Through Research: National Institute of. Summary: PD is also called primary parkinsonism or idiopathic PD. The term idiopathicmeans a disorder for which no cause has yet been found. Source: www.ninds.nih.gov http://www.ninds.nih.gov/disorders/parkinsons_disease/detail_parkinsons_disease. htm The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Parkinson disease. 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://health.nih.gov/index.asp. Under Search Health Topics, type Parkinson disease (or synonyms) into the search box, and click Search.
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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: •
Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMD®Health: http://www.webmd.com/diseases_and_conditions/default.htm
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Parkinson disease. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Parkinson disease. 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 Parkinson disease. 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://sis.nlm.nih.gov/dirline.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. Simply type in Parkinson disease (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://healthhotlines.nlm.nih.gov/. 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.
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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type Parkinson disease (or a synonym) into the search box, and click Submit Query.
Resources for Patients and Families The following are organizations that provide support and advocacy for patient with genetic conditions and their families30: •
Genetic Alliance: http://geneticalliance.org
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Genetic and Rare Diseases Information Center: http://rarediseases.info.nih.gov/html/resources/info_cntr.html
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Madisons Foundation: http://www.madisonsfoundation.org/
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March of Dimes: http://www.marchofdimes.com
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National Organization for Rare Disorders (NORD): http://www.rarediseases.org/ For More Information on Genetics
The following publications offer detailed information for patients about the science of genetics: •
What Is a Genome?: http://www.ncbi.nlm.nih.gov/About/primer/genetics_genome.html
•
A Science Called Genetics: http://publications.nigms.nih.gov/genetics/science.html
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Genetic Mapping: http://www.genome.gov/10000715
30
Adapted from the National Library of Medicine: http://ghr.nlm.nih.gov/ghr/resource/patients.
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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/archive//20040831/nichsr/ta101/ta10108.html
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
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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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PARKINSON DISEASE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine: A dopaminergic neurotoxic compound which produces irreversible clinical, chemical, and pathological alterations that mimic those found in Parkinson disease. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] 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] Actin: Essential component of the cell skeleton. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] 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
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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] 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] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU]
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Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]
Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [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] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [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] 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] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the
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antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [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] Anuria: Inability to form or excrete urine. [NIH] 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] 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] Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] 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] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion
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channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] 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] 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] 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] Autopsy: Postmortem examination of the body. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [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] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH]
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Biomolecular: A scientific field at the interface between advanced computing and biotechnology. [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] Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [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 urea: A waste product in the blood that comes from the breakdown of food protein. The kidneys filter blood to remove urea. As kidney function decreases, the BUN level increases. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bradykinesia: Abnormal slowness of movement; sluggishness of physical and mental responses. [EU] 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] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile.
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Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [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] 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] 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] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] 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 Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain
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functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [NIH] Ceramide: A type of fat produced in the body. It may cause some types of cells to die, and is being studied in cancer treatment. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] 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] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU]
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Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Fragility: Susceptibility of chromosomes to breakage and translocation or other aberrations. Chromosome fragile sites are regions that show up in karyotypes as a gap (uncondensed stretch) on the chromatid arm. They are associated with chromosome break sites and other aberrations. A fragile site on the X chromosome is associated with fragile X syndrome. Fragile sites are designated by the letters "FRA" followed by the designation for the specific chromosome and a letter which refers to the different fragile sites on a chromosome (e.g. FRAXA). [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Cirrhosis: A type of chronic, progressive liver disease. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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]
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Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] 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] 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] Colonoscopy: Endoscopic examination, therapy or surgery of the luminal surface of the colon. [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 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,
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megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] 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] Constriction: The act of constricting. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contingent Negative Variation: An increasing negative shift of the cortical electrical potentials associated with an anticipated response to an expected stimulus. It is an electrical event indicative of a state of readiness or expectancy. [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] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral
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discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] 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 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] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]
Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [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] Cultured cells: Animal or human cells that are grown in the laboratory. [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] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU]
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Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxicity: Quality of being capable of producing a specific toxic action upon cells of special organs. [NIH] De novo: In cancer, the first occurrence of cancer in the body. [NIH] Death Certificates: Official records of individual deaths including the cause of death certified by a physician, and any other required identifying information. [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] 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] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleotides: A purine or pyrimidine base bonded to a deoxyribose containing a bond to a phosphate group. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Dexterity: Ability to move the hands easily and skillfully. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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]
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Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or 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] Diuresis: Increased excretion of urine. [EU] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dopamine Agonists: Drugs that bind to and activate dopamine receptors. [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 Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents
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in medicine and scientific research. [NIH] Dysarthria: Imperfect articulation of speech due to disturbances of muscular control which result from damage to the central or peripheral nervous system. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] 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] 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] 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] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] 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] 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] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [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,
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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] 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] 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] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Evacuation: An emptying, as of the bowels. [EU] 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] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Excrete: To get rid of waste from the body. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extemporaneous: Compounded according to a physician's prescription; prepared when
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ordered; not ready-made. [NIH] Extracellular: Outside a cell or cells. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Color: Color of the iris. [NIH] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] 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] Fathers: Male parents, human or animal. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Fetal Tissue Transplantation: Transference of fetal tissue between individuals of the same species or between individuals of different species. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Gait: Manner or style of walking. [NIH]
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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] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastrointestinal: Refers to 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 Dosage: The number of copies of a given gene present in a cell or nucleus. An increase in gene dosage can result in the formation of higher levels of gene product, provided that the gene is not subject to autogenous regulation. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Products, rev: Trans-acting nuclear proteins whose functional expression are required for HIV viral replication. Specifically, the rev gene products are required for processing and translation of the HIV gag and env mRNAs, and thus rev regulates the expression of the viral structural proteins. rev can also regulate viral regulatory proteins. A cis-acting antirepression sequence (CAR) in env, also known as the rev-responsive element (RRE), is responsive to the rev gene product. rev is short for regulator of virion. [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] Genes, env: DNA sequences that form the coding region for the viral envelope (env) proteins in retroviruses. The env genes contain a cis-acting RNA target sequence for the rev protein (= gene products, rev), termed the rev-responsive element (RRE). [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] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]
Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH]
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Geriatric: Pertaining to the treatment of the aged. [EU] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Germline mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; germline mutations are passed on from parents to offspring. Also called hereditary mutation. [NIH] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [NIH] 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] 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] 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] Glucosylceramidase: A glycosidase that hydrolyzes a glucosylceramide to yield free ceramide plus glucose. Deficiency of this enzyme leads to abnormally high concentrations of glucosylceramide in the brain in Gaucher's disease. EC 3.2.1.45. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
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]
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] Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granule: A small pill made from sucrose. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Guanine: One of the four DNA bases. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair Color: Color of hair or fur. [NIH]
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Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart Valves: Flaps of tissue that prevent regurgitation of blood from the ventricles to the atria or from the pulmonary arteries or aorta to the ventricles. [NIH] Hemochromatosis: A disease that occurs when the body absorbs too much iron. The body stores the excess iron in the liver, pancreas, and other organs. May cause cirrhosis of the liver. Also called iron overload disease. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] 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] Hemophilia: Refers to a group of hereditary disorders in which affected individuals fail to make enough of certain proteins needed to form blood clots. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Hereditary mutation: A gene change in the body's reproductive cells (egg or sperm) that becomes incorporated into the DNA of every cell in the body of offspring; hereditary mutations are passed on from parents to offspring. Also called germline mutation. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heritability: The proportion of observed variation in a particular trait that can be attributed to inherited genetic factors in contrast to environmental ones. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hibernation: The dormant state in which some animal species pass the winter. It is
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characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. It is a natural physiological process in many warm-blooded animals. [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] Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] 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] Housekeeping: The care and management of property. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [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] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated with basal ganglia diseases; mental disorders; prolonged inactivity due to illness; experimental protocols used to evaluate the physiologic effects of immobility; and other conditions. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
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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
Immunodeficiency: The decreased ability of the body to fight infection and disease. [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] Impulse Control Disorders: Disorders whose essential features are the failure to resist an impulse, drive, or temptation to perform an act that is harmful to the individual or to others. Individuals experience an increased sense of tension prior to the act and pleasure, gratification, or release of tension at the time of committing the act. [NIH] Impulsive Behavior: An act performed without delay, reflection, voluntary direction, or obvious control in response to a stimulus. [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] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [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] Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [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] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -
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gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] 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] Intervertebral: Situated between two contiguous vertebrae. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [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] 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] 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] 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] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Kidney Failure, Acute: A clinical syndrome characterized by a sudden decrease in glomerular filtration rate, often to values of less than 1 to 2 ml per minute. It is usually associated with oliguria (urine volumes of less than 400 ml per day) and is always associated
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with biochemical consequences of the reduction in glomerular filtration rate such as a rise in blood urea nitrogen (BUN) and serum creatinine concentrations. [NIH] Kidney Failure, Chronic: An irreversible and usually progressive reduction in renal function in which both kidneys have been damaged by a variety of diseases to the extent that they are unable to adequately remove the metabolic products from the blood and regulate the body's electrolyte composition and acid-base balance. Chronic kidney failure requires hemodialysis or surgery, usually kidney transplantation. [NIH] Kinetic: Pertaining to or producing motion. [EU] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukemia: Cancer of blood-forming tissue. [NIH] 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] Ligase: An enzyme that repairs single stranded discontinuities in double-stranded DNA molecules in the cell. Purified DNA ligase is used in gene cloning to join DNA molecules together. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] 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] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [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
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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] Lung volume: The amount of air the lungs hold. [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]
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] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Lysosome: A sac-like compartment inside a cell that has enzymes that can break down cellular components that need to be destroyed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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]
Mammography: Radiographic examination of the breast. [NIH] 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] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of
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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] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] 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] 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 Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] 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] 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
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include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [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] Minocycline: A semisynthetic staphylococcus infections. [NIH]
antibiotic
effective
against
tetracycline-resistant
Miscarriage: Spontaneous expulsion of the products of pregnancy before the middle of the second trimester. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motor Cortex: Area of the frontal lobe concerned with primary motor control. It lies anterior to the central sulcus. [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] 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] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in
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chromosomes. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Nephropathy: Disease of the kidneys. [EU] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] 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). 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] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurologist: A doctor who specializes in the diagnosis and treatment of disorders of the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous
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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] Neuroprotective Agents: Drugs intended to prevent damage to the brain or spinal cord from ischemia, stroke, convulsions, or trauma. Some must be administered before the event, but others may be effective for some time after. They act by a variety of mechanisms, but often directly or indirectly minimize the damage produced by endogenous excitatory amino acids. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxins: Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] 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] Non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH]
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Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nurse Practitioners: Nurses who are specially trained to assume an expanded role in providing medical care under the supervision of a physician. [NIH] Oculomotor: Cranial nerve III. It originate from the lower ventral surface of the midbrain and is classified as a motor nerve. [NIH] Oliguria: Clinical manifestation of the urinary system consisting of a decrease in the amount of urine secreted. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] 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] 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] 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 Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic cancer: Cancer of the pancreas, a salivary gland of the abdomen. [NIH] Papilloma: A benign epithelial neoplasm which may arise from the skin, mucous membranes or glandular ducts. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH]
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Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Paternity: Establishing the father relationship of a man and a child. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] PDQ: Physician Data Query. PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information is available on the CancerNet Web site, and more specific information about PDQ can be found at http://cancernet.nci.nih.gov/pdq.html. [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] Pelvis: The lower part of the abdomen, located between the hip bones. [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] 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]
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] 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] Phantom: Used to absorb and/or scatter radiation equivalently to a patient, and hence to
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estimate radiation doses and test imaging systems without actually exposing a patient. It may be an anthropomorphic or a physical test object. [NIH] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] 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]
Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [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]
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Plasmids: Any extrachromosomal hereditary determinant. Plasmids are self-replicating circular molecules of DNA that are found in a variety of bacterial, archaeal, fungal, algal, and plant species. [NIH] Plastids: Self-replicating cytoplasmic organelles of plant and algal cells that contain pigments and may synthesize and accumulate various substances. Plastids are used in phylogenetic studies. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair. [NIH] 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] 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] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postoperative: After surgery. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Postural: Pertaining to posture or position. [EU] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Private Practice: Practice of a health profession by an individual, offering services on a person-to-person basis, as opposed to group or partnership practice. [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.
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(From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Program Evaluation: Studies designed to assess the efficacy of programs. They may include the evaluation of cost-effectiveness, the extent to which objectives are met, or impact. [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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Propofol: A widely used anesthetic. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein 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] Protozoal: Having to do with the simplest organisms in the animal kingdom. Protozoa are single-cell organisms, such as ameba, and are different from bacteria, which are not members of the animal kingdom. Some protozoa can be seen without a microscope. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH]
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Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [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] 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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] 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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [NIH] 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] 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]
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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] Radiculopathy: Disease involving a spinal nerve root (see spinal nerve roots) which may result from compression related to intervertebral disk displacement; spinal cord injuries; spinal diseases; and other conditions. Clinical manifestations include radicular pain, weakness, and sensory loss referable to structures innervated by the involved nerve root. [NIH]
Radioactive: Giving off radiation. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] 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] 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] 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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Reproductive cells: Egg and sperm cells. Each mature reproductive cell carries a single set of 23 chromosomes. [NIH]
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Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein. [NIH]
Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Ribonucleic acid: RNA. One of the two nucleic acids found in all cells. The other is deoxyribonucleic acid (DNA). Ribonucleic acid transfers genetic information from DNA to proteins produced by the cell. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rotenone: A botanical insecticide that is an inhibitor of mitochondrial electron transport. [NIH]
Salivary: The duct that convey saliva to the mouth. [NIH] Scatter: The extent to which relative success and failure are divergently manifested in qualitatively different tests. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH]
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Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selegiline: A selective, irreversible inhibitor of Type B monoamine oxidase. It is used in newly diagnosed patients with Parkinson's disease. It may slow progression of the clinical disease and delay the requirement for levodopa therapy. It also may be given with levodopa upon onset of disability. (From AMA Drug Evaluations Annual, 1994, p385) The compound without isomeric designation is Deprenyl. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensory loss: A disease of the nerves whereby the myelin or insulating sheath of myelin on the nerves does not stay intact and the messages from the brain to the muscles through the nerves are not carried properly. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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] 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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Small cell lung cancer: A type of lung cancer in which the cells appear small and round when viewed under the microscope. Also called oat cell lung cancer. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH]
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Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somatic cells: All the body cells except the reproductive (germ) cells. [NIH] Somatic mutations: Alterations in DNA that occur after conception. Somatic mutations can occur in any of the cells of the body except the germ cells (sperm and egg) and therefore are not passed on to children. These alterations can (but do not always) cause cancer or other diseases. [NIH] Somnolence: Sleepiness; also unnatural drowsiness. [EU] 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] Speech Intelligibility: Ability to make speech sounds that are recognizable. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal Cord Injuries: Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., wounds, gunshot; whiplash injuries; etc.). [NIH] Spinal Nerve Roots: The paired bundles of nerve fibers entering and leaving the spinal cord at each segment. The dorsal and ventral nerve roots join to form the mixed segmental spinal nerves. The dorsal roots are generally afferent, formed by the central projections of the spinal (dorsal root) ganglia sensory cells, and the ventral roots efferent, comprising the axons of spinal motor and autonomic preganglionic neurons. There are, however, some exceptions to this afferent/efferent rule. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Squamous: Scaly, or platelike. [EU] Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH]
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Squamous cell carcinoma: Cancer that begins in squamous cells, which are thin, flat cells resembling fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma. [NIH] Staphylococcus: A genus of gram-positive, facultatively anaerobic, coccoid bacteria. Its organisms occur singly, in pairs, and in tetrads and characteristically divide in more than one plane to form irregular clusters. Natural populations of Staphylococcus are membranes of warm-blooded animals. Some species are opportunistic pathogens of humans and animals. [NIH] Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] 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] Stillbirth: The birth of a dead fetus or baby. [NIH] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] 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] Substrate: A substance upon which an enzyme acts. [EU] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Supportive care: Treatment given to prevent, control, or relieve complications and side effects and to improve the comfort and quality of life of people who have cancer. [NIH] 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]
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Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] 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] Systemic: Affecting the entire body. [NIH] 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] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Tetracycline: An antibiotic originally produced by Streptomyces viridifaciens, but used mostly in synthetic form. It is an inhibitor of aminoacyl-tRNA binding during protein synthesis. [NIH] 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] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH]
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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] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Time Perception: The ability to estimate periods of time lapsed or duration of time. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [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] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transferases: Transferases are enzymes transferring a group, for example, the methyl group or a glycosyl group, from one compound (generally regarded as donor) to another compound (generally regarded as acceptor). The classification is based on the scheme
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"donor:acceptor group transferase". (Enzyme Nomenclature, 1992) EC 2. [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] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] 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] Trinucleotide Repeat Expansion: DNA region comprised of a variable number of repetitive, contiguous trinucleotide sequences. The presence of these regions is associated with diseases such as Fragile X Syndrome and myotonic dystrophy. Many chromosome fragile sites (chromosome fragility) contain expanded trinucleotide repeats. [NIH] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
Trypan Blue: An azo that that is used in protozoal infections. [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] Tumor suppressor gene: Genes in the body that can suppress or block the development of cancer. [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] Ultraviolet radiation: Invisible rays that are part of the energy that comes from the sun. UV radiation can damage the skin and cause melanoma and other types of skin cancer. UV radiation that reaches the earth's surface is made up of two types of rays, called UVA and UVB rays. UVB rays are more likely than UVA rays to cause sunburn, but UVA rays pass deeper into the skin. Scientists have long thought that UVB radiation can cause melanoma and other types of skin cancer. They now think that UVA radiation also may add to skin damage that can lead to skin cancer and cause premature aging. For this reason, skin specialists recommend that people use sunscreens that reflect, absorb, or scatter both kinds of UV radiation. [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] 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
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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] Urodynamic: Measures of the bladder's ability to hold and release urine. [NIH] URR: A blood test that compares the amount of blood urea nitrogen before and after dialysis to measure the effectiveness of the dialysis dose. [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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [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] Venoms: Poisonous animal secretions forming fluid mixtures of many different enzymes, toxins, and other substances. These substances are produced in specialized glands and secreted through specialized delivery systems (nematocysts, spines, fangs, etc.) for disabling prey or predator. [NIH] Venous: Of or pertaining to the veins. [EU] Venter: Belly. [NIH] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricles: Fluid-filled cavities in the heart or brain. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [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
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together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voice Disorders: Disorders of voice pitch, loudness, or quality. Dysphonia refers to impaired utterance of sounds by the vocal folds. [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]
Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Womb: A hollow, thick-walled, muscular organ in which the impregnated ovum is developed into a child. [NIH] 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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
205
INDEX 1 1-Methyl-4-phenyl-1,2,3,6tetrahydropyridine, 97, 160 A Acatalasia, 160, 166 Acceptor, 160, 183, 189, 201 Acetylcholine, 160, 167, 168, 188 Actin, 114, 160, 187 Adaptability, 160, 166, 167 Adenine, 107, 160, 194 Adenocarcinoma, 160, 188 Adenosine, 108, 160, 166, 191 Adenosine Triphosphate, 108, 160, 191 Adenovirus, 140, 160, 196 Adrenergic, 40, 160, 173, 175, 199 Adverse Effect, 35, 160, 197 Aerobic, 160, 186 Afferent, 98, 160, 198 Affinity, 160, 161, 163 Agonist, 42, 52, 73, 161, 173, 190 Airway, 78, 161 Airway Obstruction, 78, 161 Akinesia, 4, 51, 161 Alanine, 20, 161 Alertness, 161, 165 Algorithms, 161, 165 Alkaline, 161, 166 Alkaloid, 161, 168 Alleles, 41, 109, 126, 161, 179 Alpha-1, 122, 126, 161 Alternative medicine, 161 Amino Acid Sequence, 161, 162 Amnesia, 88, 161 Amnion, 161, 162 Amniotic Fluid, 135, 137, 161, 162 Amphetamines, 162, 168 Amygdala, 162, 164, 200 Amyloid, 19, 37, 162 Anal, 162, 183 Anatomical, 53, 162, 167, 181, 185, 196 Anemia, 121, 122, 125, 126, 131, 151, 162, 176 Anesthesia, 161, 162, 192 Aneuploidy, 120, 162 Animal model, 30, 55, 98, 162 Antagonism, 162, 166 Antibiotic, 162, 186, 200 Antibodies, 90, 114, 162, 191 Anticoagulant, 162, 193
Antidepressant, 33, 162 Antigen, 161, 162, 169, 180, 181, 185, 196 Antihypertensive, 163, 190 Anti-inflammatory, 72, 163 Antioxidant, 163, 189 Anuria, 163, 182 Anus, 162, 163, 169 Anxiety, 92, 163 Aorta, 163, 179 Apathy, 52, 60, 163 Aphasia, 103, 163 Apoptosis, 92, 108, 117, 163 Apraxia, 74, 76, 163 Aqueous, 163, 164, 172, 180 Arginine, 26, 163, 180 Arterial, 163, 180, 193 Arteries, 163, 165, 171, 179 Arterioles, 163, 165 Articulation, 163, 174 Aspartic Acid, 23, 163 Assay, 41, 163 Astrocytes, 89, 163, 164, 185, 186 Astrocytoma, 164, 178 Ataxia, 151, 164, 167, 200 Atrophy, 55, 67, 79, 87, 151, 164, 187 Attenuation, 46, 164 Atypical, 23, 52, 130, 164 Auditory, 103, 164 Autopsy, 39, 164 Axons, 164, 190, 192, 198 B Bacteria, 22, 106, 114, 118, 162, 164, 176, 185, 186, 193, 199, 201, 203 Basal Ganglia, 38, 164, 178, 180 Basal Ganglia Diseases, 164, 180 Base Sequence, 118, 164, 176 Beta-pleated, 162, 164 Bewilderment, 164, 170 Bilateral, 53, 54, 61, 72, 76, 80, 164 Bile, 164, 177, 183 Biochemical, 66, 122, 161, 164, 178, 183, 191, 197 Biological response modifier, 164, 181 Biomolecular, 43, 165 Biosynthesis, 49, 165, 197 Biotechnology, 5, 49, 113, 140, 142, 147, 149, 150, 151, 152, 165 Bladder, 58, 165, 168, 181, 187, 193, 202, 203
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Blastocyst, 165, 170 Blood Coagulation, 165, 166, 201 Blood Glucose, 165, 179 Blood pressure, 3, 125, 163, 165, 166, 180, 186 Blood urea, 165, 183, 203 Blood vessel, 129, 165, 166, 167, 182, 198, 199, 200, 201, 203 Blood-Brain Barrier, 165, 183 Bone Marrow, 141, 165, 177 Bradykinesia, 4, 165 Brain Stem, 165, 167, 187 Buccal, 135, 137, 165 C Caffeine, 61, 165, 194 Calcium, 25, 58, 166, 169, 174 Carbohydrate, 166, 178 Carcinogenic, 166, 181, 193 Carcinogens, 166, 189 Carcinoma, 166, 188, 198, 199 Cardiac, 61, 165, 166, 174, 175 Cardiovascular, 56, 144, 166, 197 Cardiovascular disease, 144, 166 Catalase, 55, 160, 166 Catecholamine, 166, 173, 191 Causal, 30, 166 Cause of Death, 166, 172 Cell Cycle, 116, 117, 166 Cell Death, 17, 40, 117, 163, 166, 187 Cell Division, 12, 13, 109, 116, 117, 129, 130, 150, 164, 166, 167, 185, 186, 191, 193 Cell proliferation, 166, 196 Cell Respiration, 166, 186, 196 Cell Survival, 27, 166 Central Nervous System, 3, 160, 161, 162, 165, 167, 168, 177, 178, 179, 183, 185, 197 Centromere, 109, 112, 167 Ceramide, 22, 167, 178 Cerebellar, 79, 164, 167, 195, 202 Cerebellar Diseases, 164, 167, 202 Cerebellum, 167, 195 Cerebral, 84, 164, 165, 167, 170, 171, 175, 176, 178, 187, 194, 200 Cerebral Cortex, 164, 167, 187, 194 Cerebral hemispheres, 164, 165, 167, 178, 200 Cerebrovascular, 164, 166, 167, 200 Cerebrum, 167, 200, 202 Cervical, 51, 167 Cervix, 167 Character, 48, 167, 172 Chin, 167, 185
Cholecystokinin, 68, 167 Cholesterol, 108, 164, 167, 171 Cholinergic, 59, 167, 168 Cholinesterase Inhibitors, 168, 173 Chromatin, 163, 168, 184 Chromosomal, 35, 117, 119, 120, 130, 131, 132, 134, 162, 168, 180, 186 Chromosome, 3, 10, 11, 13, 14, 15, 16, 18, 20, 21, 24, 26, 28, 32, 71, 86, 109, 110, 111, 112, 113, 116, 117, 119, 120, 126, 127, 130, 131, 136, 139, 162, 167, 168, 182, 183, 186, 202 Chromosome Fragility, 168, 202 Chronic, 67, 150, 168, 172, 174, 181, 182, 183, 192, 199 Chronic renal, 168, 192 Cirrhosis, 168, 179 CIS, 168, 177 Clinical Medicine, 143, 168, 192 Clinical study, 168, 170 Cloning, 11, 165, 168, 183 Coca, 168 Cocaine, 73, 168 Codon, 114, 169 Coenzyme, 33, 50, 169 Cofactor, 169, 193, 201 Cognition, 56, 169 Collagen, 169, 193 Colon, 123, 150, 169 Colonoscopy, 125, 169 Compacta, 47, 169 Complement, 169, 170, 182, 184 Complementary medicine, 94, 170 Complementation, 96, 170 Computational Biology, 147, 149, 170 Computer Simulation, 46, 170 Concentric, 170, 188 Conception, 116, 170, 176, 198 Confusion, 123, 170, 173, 202 Conjugated, 170, 171 Connective Tissue, 165, 169, 170, 172, 176, 177, 184, 190 Consciousness, 170, 172, 173, 194 Constriction, 109, 112, 170, 182 Consultation, 33, 131, 132, 135, 136, 170 Contingent Negative Variation, 79, 170 Contraindications, ii, 170 Contralateral, 89, 170, 185, 195 Control group, 35, 41, 170 Controlled clinical trial, 38, 42, 170 Controlled study, 80, 81, 170 Convulsions, 170, 188
Index 207
Coordination, 4, 32, 47, 167, 171 Cornea, 24, 171 Coronary, 166, 171 Coronary heart disease, 166, 171 Corpus, 171, 178 Corpus Striatum, 171, 178 Cortex, 163, 171, 180 Cortical, 38, 79, 170, 171, 175, 197, 200 Creatine, 51, 95, 171 Creatinine, 171, 183 Cues, 62, 99, 171 Cultured cells, 22, 171 Cyclic, 166, 171 Cysteine, 26, 171 Cystine, 171 Cytochrome, 66, 171, 189 Cytoplasm, 106, 107, 108, 114, 163, 172, 178, 184, 187, 188, 196, 200 Cytosine, 107, 172, 194 Cytoskeleton, 10, 172, 186 Cytotoxicity, 40, 172 D De novo, 32, 45, 47, 82, 117, 172 Death Certificates, 125, 172 Degenerative, 172, 186 Deletion, 119, 163, 172 Delusions, 172, 194 Dementia, 22, 36, 42, 52, 53, 57, 59, 64, 66, 75, 80, 83, 84, 85, 87, 90, 120, 155, 172, 187 Dendrites, 172, 187 Deoxyribonucleic, 107, 172, 196 Deoxyribonucleic acid, 107, 172, 196 Deoxyribonucleotides, 172 Dermis, 172, 201 Dexterity, 74, 172 Diabetes Mellitus, 172, 179 Digestion, 164, 172, 183, 199, 203 Diploid, 162, 170, 172, 186, 191, 202 Direct, iii, 38, 60, 135, 136, 137, 168, 172, 173, 195, 200 Discrimination, 137, 138, 143, 172 Disease Progression, 31, 42, 172 Disease Susceptibility, 29, 173 Disorientation, 170, 173 Dissociation, 38, 160, 173 Dissociative Disorders, 173 Distal, 173, 174, 192, 193 Diuresis, 165, 173 Donepezil, 62, 173 Dopa, 53, 75, 90, 103, 173, 183 Dopamine Agonists, 43, 54, 55, 70, 72, 173
Double-blind, 33, 45, 51, 54, 56, 89, 93, 94, 173 Drive, 37, 41, 173, 181 Drug Tolerance, 173, 201 Duodenum, 164, 173, 177, 199 Dyes, 40, 162, 173 Dysarthria, 104, 174 Dyskinesia, 56, 62, 75, 94, 156, 174 Dysplasia, 151, 174 Dystonia, 7, 40, 61, 174 Dystrophy, 151, 174 E Efficacy, 38, 42, 49, 53, 62, 85, 174, 193 Electrode, 53, 96, 174 Electrolytes, 164, 174, 182 Electrons, 163, 164, 174, 182, 189, 194 Embryo, 116, 117, 118, 126, 161, 165, 174 Empirical, 33, 174 Endemic, 174, 198 Endogenous, 40, 173, 174, 175, 188, 201 Endorphins, 174, 188 End-stage renal, 168, 174, 192 Enkephalins, 174, 188 Environmental Exposure, 174, 189 Environmental Health, 6, 103, 104, 146, 147, 174 Enzymatic, 19, 29, 166, 169, 175, 180 Epidemic, 175, 198 Epinephrine, 160, 173, 175, 188, 202 ERV, 104, 175 Erythrocytes, 162, 165, 175 Escalation, 85, 175 Essential Tremor, 151, 175 Estrogen, 39, 175 Ethnic Groups, 131, 134, 175 Eukaryotic Cells, 175, 189, 202 Evacuation, 175, 177 Excitation, 162, 175, 188 Excitatory, 175, 178, 188 Excitatory Amino Acids, 175, 188 Excrete, 163, 175, 182 Exocrine, 167, 175, 189 Exocytosis, 175, 200 Exogenous, 174, 175 Expiration, 175, 196 Expiratory, 35, 99, 175 Expiratory Reserve Volume, 175 Extemporaneous, 83, 175 Extracellular, 162, 163, 170, 176 Extrapyramidal, 32, 173, 176 Eye Color, 118, 176 Eye Infections, 160, 176
208
Parkinson Disease
F Facial, 38, 176 Facial Expression, 38, 176 Family Planning, 147, 176 Fat, 22, 165, 167, 171, 176, 183, 198 Fathers, 126, 176 Fatty acids, 95, 176 Fetal Tissue Transplantation, 86, 176 Fetus, 134, 135, 137, 141, 176, 192, 199, 203 Fibrosis, 118, 121, 125, 126, 151, 176, 196 Folate, 95, 176 Fold, 15, 35, 176 Folic Acid, 176 Forearm, 165, 176 Frameshift, 119, 176 Frameshift Mutation, 119, 176 Free Radicals, 5, 15, 163, 173, 176 Frontal Lobe, 176, 186 G Gait, 54, 62, 67, 90, 99, 167, 176 Gallbladder, 167, 177 Ganglia, 160, 164, 177, 187, 190, 198 Gas, 175, 177, 180, 188, 194, 196, 203 Gas exchange, 177, 196 Gastric, 67, 72, 177, 180 Gastric Emptying, 72, 177 Gastrin, 177, 180 Gastrointestinal, 167, 168, 175, 177, 197 Gene Dosage, 64, 177 Gene Expression, 114, 115, 151, 177 Gene Products, rev, 177 Gene Therapy, 46, 90, 98, 139, 140, 141, 142, 160, 177 Genes, env, 125, 177 Genetic testing, 68, 128, 132, 133, 134, 135, 136, 137, 138, 143, 177 Genomics, 144, 177 Genotype, 32, 69, 177, 191 Geriatric, 33, 59, 178 Germ Cells, 117, 141, 178, 185, 198 Germline mutation, 117, 178, 179 Ginkgo biloba, 96, 97, 178 Gland, 178, 184, 189, 193, 199, 201 Glioblastoma, 46, 178 Globus Pallidus, 64, 164, 171, 178 Glucose, 22, 151, 165, 172, 178, 179 Glucosylceramidase, 22, 178 Glutamate, 178 Glutamic Acid, 20, 176, 178, 188, 193 Glutathione Peroxidase, 89, 178 Glycine, 178, 188, 197 Glycoprotein, 48, 178, 201
Glycosylation, 48, 178 Governing Board, 178, 192 Granule, 178, 196 Granulocytes, 178, 183, 204 Guanine, 107, 178, 194 H Habitual, 167, 178 Hair Color, 118, 178 Haplotypes, 65, 67, 179 Headache, 165, 179 Health Services, iv, 29, 43, 148, 179 Heart attack, 166, 179 Heart Valves, 24, 179 Hemochromatosis, 134, 179 Hemodialysis, 179, 182, 183 Hemoglobin, 108, 162, 175, 179, 183 Hemoglobinopathies, 177, 179 Hemoglobinuria, 151, 179 Hemophilia, 126, 151, 179 Hemorrhage, 179, 199 Hereditary, 19, 35, 106, 107, 117, 126, 132, 178, 179, 186, 187, 190, 192, 196 Hereditary mutation, 117, 178, 179 Heredity, 109, 177, 179 Heritability, 81, 179 Heterozygotes, 73, 179 Hibernation, 69, 179 Hippocampus, 180, 187 Histamine, 180 Histidine, 23, 180 Histology, 180, 187 Histones, 109, 168, 180 Homeostasis, 9, 51, 180 Homologous, 161, 177, 179, 180, 200 Hormonal, 164, 180 Hormone, 114, 175, 177, 180, 200, 201 Housekeeping, 22, 180 Hybrid, 40, 180 Hydrogen, 160, 164, 166, 178, 180, 183, 186, 189 Hydrogen Peroxide, 166, 178, 180, 183 Hypertension, 166, 179, 180 Hypokinesia, 180, 189 Hypotension, 82, 171, 180 I Idiopathic, 11, 35, 40, 74, 75, 85, 88, 99, 156, 180 Immune response, 162, 180, 184, 203 Immune system, 180, 181, 184, 203, 204 Immunity, 161, 181 Immunodeficiency, 150, 181
Index 209
Impairment, 5, 33, 39, 60, 164, 174, 176, 181, 185, 194 Implantation, 170, 181 Impulse Control Disorders, 52, 57, 181 Impulsive Behavior, 85, 181 In vitro, 30, 41, 48, 177, 181 In vivo, 30, 47, 48, 96, 177, 181 Incontinence, 89, 181 Infancy, 144, 181 Infection, 164, 176, 181, 183, 184, 188, 204 Inflammation, 140, 163, 176, 181, 192 Informed Consent, 135, 138, 143, 181 Infusion, 60, 72, 75, 181 Initiation, 42, 67, 181, 201 Inotropic, 173, 181 Insomnia, 84, 181 Insulator, 47, 181 Interferon, 46, 181, 182 Interferon-alpha, 181, 182 Intermediate Filaments, 182, 187 Intervertebral, 182, 195 Intestinal, 167, 182, 184 Intestinal Mucosa, 167, 182 Intoxication, 98, 182, 204 Intracellular, 40, 166, 181, 182 Intravenous, 181, 182 Intrinsic, 32, 161, 182 Invasive, 181, 182, 184 Involuntary, 3, 20, 164, 175, 182, 198 Ion Channels, 163, 182 Ions, 164, 173, 174, 180, 182 Iris, 171, 176, 182, 194 Ischemia, 164, 182, 188 K Karyotype, 111, 182 Kidney Disease, 146, 151, 182 Kidney Failure, 120, 174, 182, 183 Kidney Failure, Acute, 182 Kidney Failure, Chronic, 182, 183 Kinetic, 76, 183 L Leprosy, 14, 183 Leucine, 9, 10, 11, 12, 23, 57, 183 Leucocyte, 161, 183 Leukemia, 150, 177, 183 Levo, 173, 183 Levodopa, 42, 43, 56, 60, 61, 62, 67, 70, 72, 73, 75, 76, 86, 96, 97, 100, 173, 183, 197 Ligament, 183, 193 Ligase, 14, 28, 40, 48, 65, 183 Limbic, 38, 162, 183 Linkage, 35, 41, 76, 86, 183
Lipid, 183, 189 Lipid Peroxidation, 183, 189 Liver, 115, 164, 168, 176, 177, 179, 183 Lobe, 87, 162, 183 Locomotion, 183, 191 Locomotor, 56, 76, 183 Longitudinal study, 83, 183 Lung volume, 83, 184 Lymph, 167, 184 Lymph node, 167, 184 Lymphocytes, 162, 183, 184, 204 Lymphoid, 162, 183, 184 Lymphoma, 150, 184 Lysine, 20, 180, 184 Lysosome, 22, 184 M Macrophage, 117, 184 Magnetic Resonance Imaging, 43, 55, 58, 82, 184 Major Histocompatibility Complex, 179, 184 Malabsorption, 151, 184 Malignant, 78, 150, 160, 178, 184 Malnutrition, 164, 184, 186 Mammography, 125, 184 Manic, 184, 194 Manic-depressive psychosis, 184, 194 Medial, 178, 184 Mediate, 173, 184 Mediator, 167, 173, 184, 197 Medical Records, 35, 125, 138, 185 MEDLINE, 147, 149, 151, 185 Meiosis, 116, 185, 200 Melanin, 182, 185, 191, 202 Melanocytes, 185 Melanoma, 78, 150, 185, 202 Membrane, 107, 161, 163, 169, 175, 182, 185, 188, 189, 191, 200 Memory, 161, 172, 185 Meninges, 167, 185 Mental Disorders, 180, 185, 193, 194 Mental Processes, 173, 185, 194 Mental Retardation, 130, 132, 134, 152, 185 Mesencephalic, 69, 185, 195 Microbe, 185, 201 Microbiology, 164, 185 Microglia, 163, 185, 186 Microorganism, 169, 185, 203 Microtubule-Associated Proteins, 186, 187 Microtubules, 182, 186, 187 Minocycline, 51, 186 Miscarriage, 137, 186
210
Parkinson Disease
Mitochondria, 5, 17, 78, 98, 107, 108, 120, 126, 127, 186, 189 Mitosis, 116, 163, 186 Modification, 55, 186, 194 Molecule, 10, 15, 22, 107, 108, 109, 114, 162, 164, 169, 173, 175, 179, 186, 189, 192, 195, 203 Monitor, 42, 48, 171, 186, 188 Monoamine, 67, 186, 197 Monosomy, 120, 162, 186 Morphological, 174, 185, 186 Mosaicism, 117, 186 Motor Cortex, 64, 186, 195 Movement Disorders, 31, 34, 35, 36, 39, 40, 44, 45, 68, 70, 75, 99, 155, 186, 200 Muscle Fibers, 186 Muscular Atrophy, 151, 186 Mutagens, 176, 186 Myotonic Dystrophy, 129, 151, 187, 202 N Narcosis, 180, 187 NCI, 1, 145, 168, 187, 190 Necrosis, 163, 178, 187, 197 Neocortex, 187 Neoplasia, 150, 187 Nephropathy, 182, 187 Nervous System, 46, 129, 151, 160, 167, 185, 187, 188, 190, 199 Neural, 43, 55, 56, 65, 67, 79, 160, 162, 185, 187 Neurodegenerative Diseases, 21, 164, 187 Neurofibrillary Tangles, 88, 187 Neurofilaments, 187 Neurogenic, 58, 187 Neurologic, 33, 38, 178, 187 Neurologist, 36, 72, 187 Neuronal, 12, 27, 30, 31, 40, 42, 47, 48, 64, 92, 96, 187, 190 Neurons, 4, 5, 20, 30, 31, 40, 48, 60, 69, 70, 73, 79, 168, 172, 175, 177, 183, 187, 198, 200 Neuropathy, 126, 188 Neuroprotective Agents, 31, 38, 39, 44, 45, 188 Neurotoxic, 48, 160, 188 Neurotoxins, 9, 188 Neurotransmitter, 20, 160, 163, 168, 173, 175, 178, 180, 182, 188 Neutralization, 5, 188 Nitrogen, 161, 183, 188, 203 Non-small cell lung cancer, 14, 188 Nonverbal Communication, 38, 188
Norepinephrine, 160, 173, 188 Nuclear, 107, 164, 174, 175, 177, 178, 187, 188, 196 Nuclear Envelope, 107, 188 Nuclear Pore, 188 Nuclei, 162, 174, 177, 180, 184, 186, 188, 192 Nucleic acid, 164, 172, 186, 188, 194, 196 Nurse Practitioners, 135, 189 O Oculomotor, 185, 189 Oliguria, 182, 189 Oncogene, 14, 102, 150, 189 Organelles, 106, 107, 172, 185, 189, 192 Orthostatic, 59, 82, 189 Ovaries, 134, 189, 197 Oxidation, 17, 160, 163, 171, 178, 183, 189 Oxidative Phosphorylation, 108, 189 Oxidative Stress, 15, 40, 48, 189 P Palsy, 64, 88, 189 Pancreas, 179, 189 Pancreatic, 150, 167, 189 Pancreatic cancer, 150, 189 Papilloma, 189, 196 Paralysis, 161, 163, 185, 189 Paroxysmal, 151, 189 Partnership Practice, 189, 192 Patch, 85, 190, 201 Paternity, 134, 190 Pathologic, 32, 163, 171, 190 Pathologic Processes, 163, 190 Pathologies, 36, 190 Pathophysiology, 36, 37, 190 PDQ, 145, 190 Pedigree, 14, 35, 36, 190 Peduncle, 79, 190, 195 Pelvic, 190, 193 Pelvis, 189, 190, 203 Peptide, 167, 190, 193 Perception, 35, 90, 190, 196 Pergolide, 66, 81, 83, 190 Peripheral Nerves, 183, 190 Peripheral Nervous System, 174, 187, 188, 189, 190, 192 Peroxidase, 55, 183, 190 Peroxide, 190 Phantom, 46, 190 Pharmacodynamics, 60, 61, 191 Pharmacokinetic, 73, 191 Pharmacologic, 81, 162, 191, 201 Pharmacotherapy, 73, 191
Index 211
Phenotype, 32, 35, 47, 57, 69, 88, 103, 170, 191 Phenyl, 191 Phenylalanine, 114, 191, 202 Phospholipids, 176, 191 Phosphorus, 166, 191 Phosphorylated, 48, 169, 191 Phosphorylation, 10, 108, 191 Physical Examination, 132, 191 Physiologic, 161, 165, 173, 180, 191, 195, 202 Pigment, 185, 191 Pilot study, 42, 44, 62, 191 Pitch, 191, 204 Plants, 161, 163, 168, 178, 188, 191, 201 Plasma, 34, 75, 107, 161, 162, 179, 182, 191, 197 Plasma cells, 162, 191 Plasmids, 46, 192 Plastids, 189, 192 Pleomorphic, 12, 192 Pneumonia, 170, 192 Point Mutation, 48, 192 Polycystic, 151, 192 Polymorphism, 28, 59, 136, 192 Posterior, 162, 164, 167, 182, 189, 192 Postnatal, 192, 199 Postoperative, 82, 192 Post-traumatic, 186, 192 Postural, 4, 192 Practice Guidelines, 34, 49, 148, 155, 192 Preclinical, 39, 103, 192 Precursor, 19, 173, 174, 175, 183, 188, 191, 192, 202 Prenatal, 134, 137, 174, 192 Presynaptic, 20, 26, 40, 188, 192, 200 Presynaptic Terminals, 20, 26, 192, 200 Prevalence, 83, 122, 192 Private Practice, 43, 192 Procaine, 161, 192 Program Evaluation, 99, 193 Progression, 31, 38, 39, 42, 43, 44, 54, 55, 60, 65, 75, 81, 89, 162, 193, 197 Progressive, 3, 31, 33, 42, 64, 88, 121, 168, 172, 173, 175, 183, 187, 193 Proline, 20, 23, 169, 193 Promoter, 46, 58, 67, 193 Prone, 13, 27, 120, 129, 193 Prophase, 193, 200 Propofol, 78, 193 Prospective study, 83, 183, 193 Prostate, 150, 193
Protease, 89, 193 Proteolytic, 161, 169, 193 Protocol, 42, 44, 45, 49, 140, 193 Protozoal, 193, 202 Proximal, 173, 192, 193 Psychiatric, 33, 38, 185, 193 Psychiatry, 32, 33, 59, 193 Psychic, 185, 194, 197 Psychoactive, 194, 204 Psychology, 38, 173, 194 Psychosis, 61, 76, 83, 93, 155, 194 Public Policy, 147, 194 Pulmonary, 81, 165, 179, 182, 194, 196 Pulmonary Artery, 165, 194 Pulmonary Edema, 182, 194 Pulmonary Ventilation, 194, 196 Pulse, 186, 194 Pupil, 171, 194 Purines, 164, 194, 197 Pyramidal Tracts, 176, 194 Pyrimidines, 164, 194, 197 Q Quality of Life, 33, 34, 37, 42, 48, 76, 194, 199 R Race, 9, 173, 182, 194 Racemic, 173, 194 Radiation, 173, 174, 176, 190, 194, 195, 202, 204 Radiation therapy, 173, 195 Radiculopathy, 51, 195 Radioactive, 180, 181, 188, 195 Randomized, 33, 42, 45, 47, 50, 51, 56, 93, 94, 95, 174, 195 Randomized clinical trial, 50, 195 Reality Testing, 194, 195 Receptor, 40, 47, 87, 89, 123, 162, 173, 195, 197 Recombinant, 140, 195, 203 Recombination, 177, 195 Rectum, 163, 169, 177, 181, 193, 195 Red Nucleus, 164, 195 Refer, 1, 112, 116, 118, 123, 142, 165, 169, 174, 178, 183, 194, 195, 201 Regimen, 56, 174, 191, 195 Regurgitation, 179, 195 Reliability, 86, 104, 195 Reproductive cells, 120, 130, 131, 178, 179, 195 Respiration, 186, 196 Respiratory System, 35, 196 Response rate, 33, 196
212
Parkinson Disease
Restless legs, 62, 196 Retinoblastoma, 63, 122, 150, 196 Retinoblastoma Protein, 63, 196 Retroviral vector, 177, 196 Ribonucleic acid, 114, 196 Ribose, 160, 196 Ribosome, 114, 196, 202 Rigidity, 4, 189, 191, 196 Risk factor, 25, 36, 66, 77, 84, 104, 193, 196 Rotenone, 98, 196 S Salivary, 189, 196 Scatter, 46, 190, 196, 202 Schizoid, 196, 204 Schizophrenia, 127, 196, 204 Schizotypal Personality Disorder, 196, 204 Sclerosis, 78, 123, 151, 196 Screening, 11, 33, 81, 125, 134, 135, 137, 168, 190, 196 Sedative, 78, 197 Seizures, 178, 189, 197 Selegiline, 42, 197 Semen, 193, 197 Semisynthetic, 186, 197 Sensory loss, 195, 197, 200 Sequencing, 142, 197 Sequester, 197, 200 Serine, 23, 28, 197 Serotonin, 188, 191, 197 Serum, 51, 63, 169, 183, 197 Sex Characteristics, 197, 200 Sex Determination, 151, 197 Side effect, 141, 144, 160, 173, 197, 199, 201 Signs and Symptoms, 4, 5, 23, 128, 129, 134, 197 Small cell lung cancer, 197 Small intestine, 173, 180, 197 Smooth muscle, 162, 165, 180, 198 Social Environment, 194, 198 Social Work, 131, 198 Soft tissue, 165, 198 Soma, 198 Somatic, 117, 120, 131, 185, 186, 190, 198 Somatic cells, 117, 120, 131, 185, 186, 198 Somatic mutations, 120, 198 Somnolence, 86, 198 Spasm, 185, 198 Specialist, 36, 135, 157, 198 Species, 144, 175, 176, 178, 179, 180, 182, 185, 186, 192, 194, 198, 199, 202, 203, 204 Speech Intelligibility, 35, 104, 198
Sperm, 116, 117, 120, 129, 130, 131, 134, 141, 168, 178, 179, 195, 198 Spinal cord, 163, 164, 165, 167, 185, 187, 188, 190, 194, 195, 198 Spinal Cord Injuries, 195, 198 Spinal Nerve Roots, 195, 198 Sporadic, 4, 19, 29, 32, 40, 41, 48, 75, 86, 187, 196, 198 Squamous, 188, 198, 199 Squamous cell carcinoma, 188, 198, 199 Staphylococcus, 186, 199 Stem Cells, 55, 95, 199 Stereotactic, 78, 87, 199 Stillbirth, 132, 199 Stimulant, 165, 180, 199 Stimulus, 170, 173, 174, 175, 181, 182, 199, 200 Stomach, 177, 180, 197, 199 Stool, 169, 181, 199 Strand, 107, 199 Stress, 15, 17, 30, 97, 166, 189, 199 Striatum, 40, 199 Stroke, 6, 9, 45, 84, 125, 146, 166, 188, 199 Subacute, 88, 181, 199 Subspecies, 198, 199 Substrate, 48, 199 Supplementation, 95, 199 Support group, 32, 39, 45, 49, 199 Supportive care, 190, 199 Sympathomimetic, 173, 175, 188, 199 Symphysis, 167, 193, 200 Symptomatic, 38, 42, 45, 200 Symptomatic treatment, 42, 200 Synapse, 160, 192, 200, 202 Synapsis, 200 Synaptic, 12, 20, 27, 40, 41, 48, 188, 200 Synaptic Vesicles, 12, 20, 48, 200 Systemic, 98, 163, 165, 175, 181, 187, 195, 200 T Telangiectasia, 151, 200 Telencephalon, 164, 167, 200 Terminator, 169, 200 Testosterone, 53, 200 Tetracycline, 186, 200 Thalamic, 89, 164, 200 Thalamic Diseases, 164, 200 Thermal, 173, 200 Threonine, 20, 197, 200 Threshold, 35, 180, 200 Thrombin, 193, 201 Thrombomodulin, 193, 201
Index 213
Thrombosis, 193, 199, 201 Thyroid, 134, 201, 202 Thyroid Gland, 134, 201 Thyroid Hormones, 201, 202 Time Perception, 96, 201 Tolerance, 39, 160, 201 Tomography, 65, 87, 92, 201 Tonicity, 174, 201 Toxic, iv, 22, 24, 106, 172, 174, 181, 188, 201 Toxicity, 41, 140, 201 Toxicology, 147, 201 Toxin, 54, 201 Trace element, 51, 201 Trachea, 201 Transcription Factors, 115, 201 Transdermal, 85, 201 Transfection, 165, 177, 201 Transferases, 178, 201 Translation, 46, 114, 115, 177, 202 Transmitter, 160, 163, 173, 175, 182, 185, 188, 200, 202 Transplantation, 55, 69, 94, 168, 183, 184, 202 Trauma, 164, 179, 187, 188, 200, 202 Tremor, 3, 40, 74, 82, 185, 189, 202 Trinucleotide Repeat Expansion, 129, 202 Trinucleotide Repeats, 202 Trisomy, 120, 162, 202 Trypan Blue, 40, 202 Tuberous Sclerosis, 151, 202 Tumor suppressor gene, 13, 14, 196, 202 Tyrosine, 28, 55, 173, 202 U Ubiquitin, 12, 14, 16, 27, 28, 40, 48, 65, 68, 187, 202 Ultraviolet radiation, 117, 202 Uremia, 182, 202 Urethra, 193, 202, 203 Urinary, 89, 168, 181, 189, 202
Urine, 163, 165, 171, 173, 179, 181, 182, 189, 202, 203 Urodynamic, 58, 203 URR, 21, 203 Uterus, 134, 167, 171, 189, 203 V Vaccine, 193, 203 Vacuoles, 189, 203 Vascular, 84, 172, 181, 201, 203 Vasodilator, 173, 180, 203 VE, 11, 43, 73, 79, 203 Vector, 47, 139, 140, 203 Vein, 182, 188, 203 Venoms, 188, 203 Venous, 193, 203 Venter, 203 Ventral, 69, 189, 198, 203 Ventricles, 179, 203 Venules, 165, 203 Vesicular, 40, 67, 203 Veterinary Medicine, 147, 203 Viral, 88, 90, 139, 177, 203 Virulence, 201, 203 Virus, 139, 182, 196, 203 Viscera, 198, 203 Vitro, 48, 134, 203 Vivo, 48, 204 Voice Disorders, 48, 204 Volition, 182, 204 W White blood cell, 117, 184, 191, 204 Windpipe, 201, 204 Withdrawal, 88, 204 Womb, 203, 204 X Xenograft, 162, 204 X-ray, 188, 195, 199, 204 Y Yeasts, 191, 204 Z Zygote, 170, 186, 204 Zymogen, 193, 204
