Myotonic Dystrophy - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

MYOTONIC DYSTROPHY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Myotonic Dystrophy: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00743-6 1. Myotonic Dystrophy-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 myotonic dystrophy. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON MYOTONIC DYSTROPHY ........................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Myotonic Dystrophy..................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 26 The National Library of Medicine: PubMed ................................................................................ 27 CHAPTER 2. NUTRITION AND MYOTONIC DYSTROPHY ................................................................. 73 Overview...................................................................................................................................... 73 Finding Nutrition Studies on Myotonic Dystrophy.................................................................... 73 Federal Resources on Nutrition ................................................................................................... 74 Additional Web Resources ........................................................................................................... 75 CHAPTER 3. ALTERNATIVE MEDICINE AND MYOTONIC DYSTROPHY ........................................... 77 Overview...................................................................................................................................... 77 National Center for Complementary and Alternative Medicine.................................................. 77 Additional Web Resources ........................................................................................................... 80 General References ....................................................................................................................... 81 CHAPTER 4. PATENTS ON MYOTONIC DYSTROPHY ....................................................................... 83 Overview...................................................................................................................................... 83 Patents on Myotonic Dystrophy.................................................................................................. 83 Patent Applications on Myotonic Dystrophy .............................................................................. 86 Keeping Current .......................................................................................................................... 90 CHAPTER 5. BOOKS ON MYOTONIC DYSTROPHY ........................................................................... 91 Overview...................................................................................................................................... 91 Chapters on Myotonic Dystrophy................................................................................................ 91 CHAPTER 6. PERIODICALS AND NEWS ON MYOTONIC DYSTROPHY ............................................. 93 Overview...................................................................................................................................... 93 News Services and Press Releases................................................................................................ 93 Academic Periodicals covering Myotonic Dystrophy .................................................................. 95 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 99 Overview...................................................................................................................................... 99 NIH Guidelines............................................................................................................................ 99 NIH Databases........................................................................................................................... 101 Other Commercial Databases..................................................................................................... 103 The Genome Project and Myotonic Dystrophy.......................................................................... 103 APPENDIX B. PATIENT RESOURCES ............................................................................................... 107 Overview.................................................................................................................................... 107 Patient Guideline Sources.......................................................................................................... 107 Associations and Myotonic Dystrophy...................................................................................... 109 Finding Associations.................................................................................................................. 110 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 113 Overview.................................................................................................................................... 113 Preparation................................................................................................................................. 113 Finding a Local Medical Library................................................................................................ 113 Medical Libraries in the U.S. and Canada ................................................................................. 113 ONLINE GLOSSARIES................................................................................................................ 119 Online Dictionary Directories ................................................................................................... 119 MYOTONIC DYSTROPHY DICTIONARY ............................................................................. 121

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INDEX .............................................................................................................................................. 165

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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 myotonic dystrophy 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 myotonic dystrophy, 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 myotonic dystrophy, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on myotonic dystrophy. 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 myotonic dystrophy, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on myotonic dystrophy. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON MYOTONIC DYSTROPHY Overview In this chapter, we will show you how to locate peer-reviewed references and studies on myotonic dystrophy.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and myotonic dystrophy, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “myotonic dystrophy” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •

Hereditary Components in the Neurodegenerative Diseases Alzheimer's Disease and Myotonic Dystrophy Source: Neurobiology of Aging. 15(2): 243-245. March-April 1994. Summary: This article illustrates the role of hereditary elements in neurodegenerative diseases from recent data on Alzheimer's disease (AD) and myotonic dystrophy (MD). It reports that there appears to be a direct correlation of the size of p(CTG)n repeat in blood DNA with the severity and anticipation of MD, and that the size of the p(CTG)n repeat can vary in different tissues of the same individual. The author has found that the presence of the p(CTG)n repeat interferes with the transcription mechanism. Early studies have hypothesized that the locus of the hereditary factor, the dynamic mutation, may cause abnormal transcription of the gene and perhaps other cis-contiguous genes.

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The gene responsible for clinical expression of disease may be in an abnormally expressed region and the degree of expression of the abnormal mRNA species may be related to the length of the p(CTG)n repeat in the affected tissue. Different genes in the affected region may be responsible for expression in different tissues. As for AD, researchers are now interested in finding how the specific APP770(717val-) mutation leads to phenotypic expression distinct from other mutations in APP that cause vascular hemorrhages or are found in controls. It is speculated that if the APP770(717val-) is an accelerator of AD due to the deposition of unprocessed APP extracellularly, the center of gravity of relevant APP metabolism and plaque phenomenology may shift outside the cell. 15 references. (AA-M). •

Effects of Myotonic Dystrophy and Duchenne Muscular Dystrophy on the Orofacial Muscles and Dentofacial Morphology Source: Acta Odontologica Scandanavica. 56(6): 369-374. December 1998. Summary: This article reviews two of the less rare myopathies: myotonic dystrophy (MyD) and Duchenne muscular dystrophy (DMD), and their effect on the orofacial muscles and dentofacial morphology. A high prevalence of malocclusions was found among the patients affected by these diseases. The development of the malocclusions in MyD patients seems to be strongly related to the vertical aberration of their craniofacial growth due to the involvement of the masticatory muscles in association with the possibly less affected suprahyoid musculature. Thus, a new situation is established around the teeth transversely. The lowered tongue is not in a position to counterbalance the forces developed during the lowering of the mandible by the stretched facial musculature. This may affect the teeth transversely, decreasing the width of the palate and causing posterior crossbite. The lowered position of the mandible, in combination with the decreased biting forces, may permit an overeruption of the posterior teeth, with increased palatal vault height and development of anterior open bite. The development of the malocclusions in DMD patients also seems to be strongly related to the involvement of the orofacial muscles by the disease. However, the posterior crossbite is not developed owing to the narrow maxillary (upper jaw) arch, as is the case in MyD patients. On the contrary, the posterior crossbite in DMD is due to the transversal expansion of the mandibular arch, possibly because of the decreased tonus of the masseter muscle near the molars, in combination with the enlarged hypotonic tongue and the predominance of the less affected orbicularis oris muscle. 2 figures. 33 references.

Federally Funded Research on Myotonic Dystrophy The U.S. Government supports a variety of research studies relating to myotonic dystrophy. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions.

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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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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 myotonic dystrophy. 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 myotonic dystrophy. The following is typical of the type of information found when searching the CRISP database for myotonic dystrophy: •

Project Title: ABERRANT RNA PROCESSING IN HUMAN DEVELOPMENT Principal Investigator & Institution: Shamoo, Adil Yousif.; Biochemistry and Cell Biology; Rice University 6100 S Main Houston, Tx 77005 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from applicant's description): This proposal uses a combination of biochemical and x-ray crystallographic approaches to study the structural basis of aberrant RNA processing in genetic disease. CUG-binding protein (CUG-BP), ELAVtype RNA-binding protein (ETR) -1 and -3 are proteins responsible for developmentally regulated splice site selection in a variety of tissues and cell types. These proteins contain 3 copies of the RNA recognition motif (RRM) and participate in a wide range of RNA processing events including, splicing, transport and mRNA turnover. CUG-BP, ETR-1 and ETR-3 specifically effect splice site selection in striated muscle tissue. CUGBP was first isolated in connection with myotonic dystrophy (DM), a genetic disease that results from an expansion of CUG repeats in an untranslated region of the myotonin kinase gene and results in symptoms from mild myotonia to severe retardation at birth. DM is an unfortunately common disease (1 in 8000 births). CUG-BP also interacts with CUG-rich sequences found in a number of other mRNAs. Alteration of in vivo levels of CUG-BP, ETR- 1 or ETR-3 result in tissue specific changes in splicing that appear to mimic either developmental or disease related RNA processing defects. This award would be used to examine how RNA sequences already involved in ribonucleoprotein complexes are read or "scanned" by other RNA binding proteins such as those involved in alternate splicing. Crystallographic conditions required to determine the three-dimensional structure of CUG-BP, ETR-1, and ETR-3 bound to their physiologically relevant RNA targets using x- ray crystallography will also be determined. The results derived from this proposal will significantly broaden our understanding of how aberrant RNA splicing occurs and address fundamental aspects of RNA metabolism to provide immediate insights to investigators working in the field of human disease pathogenesis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: AUTOMATED DETECTION OF GENE DUPLICATIONS OR DELETIONS Principal Investigator & Institution: Merchant, Fatima; Lead Research Engineer; Advanced Digital Imaging Research, Llc 2450 S Shore Blvd, Ste 305 League City, Tx 775732997 Timing: Fiscal Year 2004; Project Start 01-APR-2000; Project End 19-MAR-2006 Summary: (provided by applicant): This project will further develop automated instrumentation and image analysis techniques to detect gene duplications or deletions in interphase FISH, which are difficult to detect by routine cytogenetics. There is a growing list of genetic disorders that result from chromosomal anomalies, related to

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either duplications or deletions. These include: (1) neuropathies; Charcot-Marie-Tooth Disease (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP), (2) neurological disorders; Pelizaeus-Merzbacher Disease (PMD) and X-Linked Spastic Paraplegia (SPG2), (3) muscular wasting disorders; Duchene (DMD) and Becker Muscular Dystrophy (BMD), (4) contiguous-gene syndromes; Smith-Magenis Syndrome (SMS). Our approach is to use readily available DNA probes, followed by automated genetic screening to detect duplications/deletions. We will develop an imaging system for the automated identification of interphase cells, and use sophisticated image analysis for high-resolution detection and separation of microscopic rearrangements. In the Phase I project we evaluated the feasibility of newly developed imaging algorithms, for effectively and precisely identifying the separation of FISH dot duplicates. Algorithms were developed for automatically (1) segmenting dots, (2) computing the integrated fluorescence intensity of dots, (3) determining the separation distance, and (4) classifying duplicates and single dots. In Phase II we will incorporate the newly developed imaging algorithms into our automated imaging system, and test the prototype clinically. We will also develop and implement three-dimensional modeling techniques to obtain an unbiased estimate of the spatial distance between duplicated genes. Phase III will commercialize the instrument. Computer automation will make genetic screening practical on a large scale by reducing costs and relieving humans of tedious duties. This approach will be most valuable to medical genetics, particularly for screening CMT1A/HNPP, PMD/SPG2, DMD/BMD, and SMS. Duplications have also been identified for the Prader-Willi /Angelman syndrome region that result in autism. Duplications, such as for 22ql 1.2 and 17pl 1.2 have been described and result in a rather mild phenotype. But duplications of the Williams syndrome region have not been described and thus, the phenotype is unknown. The ability to screen patients for duplications by interphase FISH analysis will likely identify a large number of individuals that would benefit from medical intervention. It may uncover syndromes that previously had no identifiable etiology. This will provide a screening test and eventually a diagnostic test for those individuals with perhaps mild phenotypes, such as learning disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHCR:A PROTEIN IN MAMMALIAN MUSCLE DIFFERENTIATION Principal Investigator & Institution: Wang, Edith H.; Pharmacology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): The long-term goal of this research is to unravel the molecular mechanism of muscle differentiation and to provide new information that may lead to therapeutic approaches for myotonic dystrophy. The activation of muscle differentiation involves both positive and negative signals. While much attention has been placed on proteins that promote muscle differentiation, the importance of negative regulatory pathways has been under emphasized. Disrupting the delicate balance between positive and negative signals can lead to the development of disease. The focus of this proposal will be to investigate the function of a novel protein CHCR that we hypothesize antagonizes muscle differentiation, which is in striking contrast to its close relative Muscleblind (at 49% identity), a Drosophila protein essential for muscle formation. CHCR also displays approximately 80% homology to proteins implicated in myotonic dystrophy (DM l) and binds to expanded repeat transcripts found in the nuclei of DM1 cells. Based on our preliminary studies, we hypothesize that CHCR is an inhibitor of muscle differentiation and that its mechanism of action requires changes in

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gene expression mediated by direct DNA binding. To test this hypothesis, we will examine the effects of CHCR overexpression and reducing CHCR protein levels by morpholino antisense oligonucleotides and RNA interference on muscle differentiation in C2C12 mouse myoblasts. We also propose to map the part of CHCR that is required for suppression of muscle differentiation. This information will help guide the protein interaction studies described below. The techniques of suppression subtractive hybridization and DNA microarrays will be used to identify changes in gene expression mediated by CHCR function. The involvement of direct DNA binding will be investigated by chromatin immunoprecipitation followed by the probing of DNA microarrays (ChiP-chip) and a random site selection technique. A yeast two-hybrid screen and coimmunoprecipitation experiments will be carried out to identify CHCRbinding proteins required for its antagonistic effect on mammalian muscle differentiation. The identification of direct gene targets and CHCR interacting proteins will provide the tools to further investigate CHCR function in muscle differentiation. Our long-term goal is increase our understanding of negative regulatory mechanisms underlying mammalian muscle differentiation. Such findings may reveal new avenues for therapy development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLONING/CHARACTERIZATING A MYOTONIC DYSTROPHY LOCUS Principal Investigator & Institution: Ranum, Laura P.; Professor; Neurology; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002; Project Start 01-JUN-1997; Project End 31-MAY-2005 Summary: Myotonic dystrophy (DM) is a multisystem disease and the most common form of muscular dystrophy in adults. In 1992, one form of DM was shown to be caused by an expanded CTG repeat in the 3' untranslated region of the myotonin protein kinase gene (DMPK) on chromosome 19. Although multiple theories attempt to explain how the CTG expansion causes the broad spectrum of clinical features in DM, there is no consensus about how this mutation, which does not alter the protein coding region of a gene, affects cellular function. We have identified a five-generation family (MN1) with a genetically distinct form of myotonic dystrophy. Affected members have the characteristic features of DM (myotonia, proximal and distal limb weakness, frontal balding, cataracts, and cardiac arrhythmias) but do not have the chromosome 19 mutation. We have mapped the disease locus (DM2) for the MN1 family to a small region of chromosome 3 (Nature Genetics 19:196- 198). This proposal outlines a strategy to identify and characterize the DM2 locus. Understanding what is common to chromosome 19 DM (now designated DM1 by the DM consortium) and DM2 at the molecular level should shed light on the mechanisms responsible for the broad constellation of clinical features present in both diseases. Our specific aims are: 1) to develop a high-resolution map of the DM2 region (0.5-1.0 cM) using haplotype and linkage disequilibrium analysis of 29 DM2/PROMM families from Minnesota and Germany; 2) to identify the expressed genes and repeat motifs in the region and prioritize candidates based on homology and expression patterns; 3) to identify the DM2 mutation; 4) to characterize the DM2 gene and investigate whether or not the pathogenic molecular changes found in DM2 are part of a common pathway also affected in DM1; 5) to determine whether molecular changes affecting RNA splicing, CUG binding proteins, and apamin receptors are similar to those found in DM1. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: EFFECTS OF SOMATOKINE IN MYOTONIC DYSTROPHY TYPE 1 Principal Investigator & Institution: Moxley, Richard T.; Professor; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: These phase 1 studies examine a possible new treatment for myotonic dystrophy type1 (DM1), the most common form of adult muscular dystrophy. At present no treatment exists to reverse its progressive wasting and weakness. Low levels of testosterone and growth hormone, as well as insulin resistance, appear to contribute to the muscle loss, but therapeutic trials to reverse these hormonal abnormalities have failed to produce significant improvement. A previous trial of insulin-like growth factor1 [IGF1] has offered promise. Treatment with rhlGF1 increased strength, protein synthesis, and insulin action in 7 patients but side effects caused 2 to drop out. A new, better tolerated, longer acting, preparation of rhlGF1, is now available from INSMED. It is SomatoKine, rhlGF1 in complex with recombinant human IGF binding protein 3, and it will be used in this proposal. Preliminary studies show it is safe and well tolerated in healthy adults, diabetics, and older women treated after hip fracture. We will evaluate SomatoKine in DM1. The aim of this proposal is to evaluate the safety and feasibility of daily subcutaneous injections of SomatoKine for treatment of muscle wasting and weakness by performing two sequential studies, each involving 15 patients with DM1: 1st) An initial 24-Week Dose Escalation Study of SomatoKine [0.5, 1.0, and 2.0 mg/kg, with each dose given daily for 8 weeks] to identify an "optimal dose" based upon the side effects, drug levels, and efficacy [dual energy x-ray absorptiometry (DEXA); quantitative myometry; manual muscle strength testing] observed at each dose; 2nd) A subsequent 24-Week study of SomatoKine using an "Optimal Dose" to demonstrate its safety and feasibility as a daily treatment for a six month period. In addition, we will search for evidence of altered signaling along the intracellular pathway for IGF1 by measuring phosphorylation of p70S6K in needle muscle biopsy specimens obtained from 10 DM1 patients in the 24-Week "Optimal Dose" SomatoKine Study and from 10 age-gender matched normal volunteers who will receive SomatoKine for only two days. Specimens will be obtained from vastus lateralis muscle before and after two days of "optimal dose" treatment. These studies will test our hypothesis that supraphysiologic levels of IGF1 are safe and well tolerated and provide preliminary data regarding efficacy (reversal of muscle wasting and weakness.) If the results of this project prove promising, we plan to carry out a larger, multi-center, phase 2, controlled trial of SomatoKine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE EXPRESSION AND DYSFERLIN-RELATED DYSTROPHIES Principal Investigator & Institution: Brown, Robert H.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002 Summary: (provided by applicant): Limb girdle muscular dystrophy type 2B (LGMD 2B) and Miyoshi myopathy (MM) are caused by defects in a gene that encodes a newly identified protein "dysferlin". The long-term objectives of this proposal are to characterize the biological properties of dysferlin and its role in the pathogenesis of LGMD 2B and MM and to initiate studies of cell therapy in these diseases. The specific aims are to: (1) Characterize dysferlin gene mutations and abnormalities of dysferlin protein expression in patients with MM and LGMD 2B and use this information to extend our studies of dysferlin as a novel muscle membrane protein. (2) Use

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conventional methods (immunoprecipitation, yeast two-hybrid analyses) to identify proteins that interact with normal and mutant dysferlin. (3) Use chip-based mRNA expression arrays to analyze dysferlin-deficient human muscle to identify changes of muscle gene expression that are either common to all dystrophies or specific to the dysferlinopathies. (4) Validate results of expression arrays and characterize genes that are unique to each of the dystrophies and begin to test new hypotheses about the molecular pathogenesis of muscle degeneration in the dysferlinopathies. (5) Analyze muscle stem cell (SP cell) populations in MM and LGMD-2B and the feasibility of SP therapy in a mouse model of dysferlin deficiency. These studies will be important because: (1) the dysferlinopathies constitute a significant proportion of all LGMD; (2) the studies in Aims 1-3 will illuminate aspects of the normal biological properties of this novel protein; (3) studies of pathological muscle in Aims 1-4 will contribute directly to understanding the pathogenesis of LGMD, MM and other muscular dystrophies (including facioscapulohumeral and myotonic dystrophy, included as comparative disease controls); and (4) the investigations in Aim 5 will contribute to the development of therapy for these types of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INFULENCE OF DM LOCUS ON A DISTANT GENE (FCGRT) IN MYOT* Principal Investigator & Institution: Junghans, Richard P.; Beth Israel Deaconess Medical Center St 1005 Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-JUL-2004 Summary: (provided by applicant): Myotonic dystrophy (DM) is caused by an expanded trinucleotide repeat that is present in the 3' untranslated region of the mRNA of DM protein myotonin kinase (DMPK). After many investigations, it appears that the DM syndrome is a result of diverse mechanisms influencing different genes: (i) effects of the repeat on the net expression of protein of DMPK, (ii) effects of the trinucleotiderepeat-containing mRNA itself on cell or nuclear functions, and (iii) effects of the repeat on the chromosomal structure in this region. The research proposal addresses a further potential mechanism: long-range effects of the DM disease locus on a distant gene, specifically FCGRT. The'FCGRT gene encodes the heavy chain of the FcRB, the IgG A protection receptoralpha expressed in vascular endothelial cells that rescues endocytosed IgG antibody from catabolism. The protection mechanism is depressed in myotonic dystrophy, compatible with underexpression of the FcRB; receptor. FCGRT has been mapped to the same chromosomal band (19ql3.3) as the DM locus, but it is 4 megabases distant. The long-range effects may be confined to the FCGRT on the same chromosome (cis) or may be experienced by FCGRT on both chromosomes (trans) in affected individuals. The degree of loss of IgG protection is compatible with half as much expression of FCGRT, that would be compatible with a monoallelic suppression. The presence of the DM and FCGRT genes in the same chromosomal band suggests that their co-localization may be more than coincidental (p=0.003), i.e., that there is a cismechanism by which DM suppresses the FCGRT gene. If the mechanism is cis, it implies an unusual, and perhaps novel, type of long-range interaction on the DM chromosome, such as RNA "painting" in analogy to Xist-induced X chromosome inactivation. For specific aim , we propose: to demonstrate FCGRT suppression as the mechanism of IgG hypericatabolism in DM, to establish whether the FCGRT suppression is by a cis or trans mechanism, to begin to elucidate the molecular basis for these mechanisms. Understanding the means of FCGRT suppression in DM may

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suggest new directions of research by which the multisystem/multigene phenotype of DM may be explained. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INSTABILITY OF TRIPLET REPEATS IN MAMMALIAN CELLS Principal Investigator & Institution: Wilson, John H.; Assistant Professor; Biochem and Molecular Biology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-APR-1987; Project End 30-NOV-2005 Summary: Expansions of trinucleotide (triplet) repeats at specific sites in the human genome cause a number of neurological diseases, including myotonic dystrophy, Huntington disease, fragile X syndrome, and several others. At the myotonic dystrophy locus, normal individuals have up to 30-40 CTG/CAG repeats, whereas affected individuals may have up to several thousand repeats. CTG/CAG repeats have a propensity to form a variety of stable secondary structures in vitro, and it is thought that these unusual structures interfere with aspects of DNA metabolism in cells, leading to repeat expansion and disease. Studies in E. coli and S. cerevisiae have shown that triplet repeat stability is sensitive to processes that expose single strands of DNA, including transcription, replication, repair, and recombination. This application seeks to develop novel selective systems for investigation CTG/CAG triplet repeat stability in vertebrate cells. Instability during recombination and the effects of triplet repeats on the recombination processes, which have already been demonstrated at the APRT locus in CHO cells, will be defined using a variety of tandem duplication substrates, I-SceImediated double-strand breaks, and ERCC1-deficient cells. Instability of repeats due to all causes will be investigated using a novel, direct-selection assay based on the lengthdependent effects on gene expression by intronic CAG repeats, which have already been demonstrated. Long repeats placed in the intron of the HPRT minigene, which render it HPRT , can be used to select for repeat contractions (HPRT- to HPRT+). Similarly, short CAG repeats that are compatible with gene expression can be used to select for repeat contractions (HPRT- to HPRT+). Similarly, show CAG repeats that are compatible with gene expression can be used to select for expansions (HPRT- to HPRT+). The boundaries for these length- dependent effects will be defined, the mechanism of interference will be determined, and appropriate CAG-containing, HPRT-minigene substrates will be deposited in the chromosomes of vertebrate cells. These substrates will allow testing of the effects of genes involved in replication, repair, and in recombination and cell treatments that stress these processes. In summary, we propose and integrated and comprehensive set of experiments to define the molecular basis of the CTG/CAG repeat instability that underlies myotonic dystrophy and other neurological diseases. These studies will also provide a set of experimental reagents that will e useful in the design and evaluation of potential therapeutic strategies directed at preventing expansion or promoting contraction of CTG/CAG repeats. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTERACTIONS OF MYOTONIC DYSTROPHY PROTEIN KINASE Principal Investigator & Institution: Epstein, Henry F.; Professor; Neurology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-MAY-1996; Project End 31-MAY-2005 Summary: (adapted from applicant's abstract): Myotonic Dystrophy Protein Kinase (DMPK) is encoded by the Myotonic Dystrophy 1 (DM1) locus. Studies on human tissues and cultured cells suggest that haploinsufficiency affecting DMPK expression is

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a significant consequence affecting DMPK expression is a significant consequence of the dCTG repeat expansion mutations that cause DM1. These mutations may affect other genes as well by several mechanisms. Studies of the DMPK knockout and transgenic mice have reported skeletal and cardiac myopathy, cardiac arrhythmias, and in our preliminary results, altered synaptic plasticity in the central nervous system. Knockout of the neighboring gene, Six5 or DMAHP (DM associated homeodomain protein) leads to cataracts. The CUG expansion in mRNA may sequester proteins required for splicing of the RNAs of multiple genes. On the other hand, loss-of-function mutations in other serine-threonine protein kinases can also lead to autosomal dominant traits with variable expressivity and pleiotropy such as in Coffin-Lowry and Peutz-Jeghers Syndromes. These results support continued study of DMPK with respect to understanding the pathogenesis of DM1. DMPK is also representative of a new group of serine-threonine protein kinases active in cell-cycle control, cell differentiation, and cytoskeleton organization. At least two other human protein kinases are also members. Preliminary studies in our laboratory suggest that DMPK may serve as a nexus for cross-talk or convergence between distinct signaling networks. DMPK can interact with two well known proteins that mark distinct signaling pathways: chemically stimulated Raf-1 kinase and the cytoskeleton-linked Rho family GTPase Rac-1. In order to more rigorously establish the biochemical, cellular, and physiological significance of these interactions and further understand the responsible mechanisms, we propose the following Specific Aims: 1) to study the interactions of Rac-1 and Raf-1 kinase with DMPK as purified recombinant proteins as tests for direct functional activation and synergy and their structural basis in the DMPK molecule; 2) to test for cross-talk or convergence of Rac-1 and Raf-1 kinase signaling upon DMPK in cultured myogenic and neurogenic cells in culture and verify its structural basis in the DMPK molecule; and 3) to verify cross-talk in vivo between Rac-1 and Raf-1 kinase upon DMPK in brain and muscle by constructing and studying mutant mouse lines derived from crosses of wildtype controls or DMPK knockouts with dominant negative mutant transgenes expected to alter the activation of DMPK by Rac-1 and/or Raf-1 kinase. Accomplishment of these objectives would suggest that DMPK integrates different signals in its modulation of function in muscle and nerve. These results would clearly provide a foundation for better understanding of the role that DMPK may play in the pathogenesis of DM1 and for a potentially rational design of therapeutics. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: INTESTINAL IMMUNOGLOBULIN

AND

PLACENTAL

FC-RECEPTORS

FOR

Principal Investigator & Institution: Simister, Neil E.; Professor; Biology; Brandeis University 415 South Street Waltham, Ma 024549110 Timing: Fiscal Year 2002; Project Start 01-FEB-1991; Project End 30-APR-2005 Summary: (adapted from investigator's abstract): The neonatal Fc receptor, FcRn, transports IgG antibodies from mother to offspring. The acquisition of maternal antibodies is essential for immunologic defense, although autoantibodies and immune complexes of live pathogens are potentially harmful to the neonate. FcRn also protects circulating IgG from catabolism, controlling the level of serum IgG, and prolonging the time for which antibodies of a particular specificity are present at useful concentrations. FcRn serves both of these functions by transporting IgG across cells by a pathway that avoids lysosomal degradation. The long-term objective of this proposal is to describe in molecular terms how FcRn transports IgG across cells. The immediate goal is to identify and characterize amino acid sequences in the cytoplasmic domain of FcRn that direct

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uptake and targeting of the receptor. This will be done by making specific alterations in the receptor by site-directed mutagenesis, and analyzing the effects of the mutations in a cell culture model of IgG transport. The subcellular route of transport by FcRn will be determined by confocal and immunoelectron microscopy, and mutations that divert FcRn from this pathway will be identified. An FcRn-binding peptide will be used to study the effect of IgG on FcRn transport. Such a peptide will also be used to explore the possibility of blocking the interaction of IgG and FcRn. Related aims are to investigate the regulation of transcription of FcRn, and to determine whether decreased transcription causes the elevated IgG catabolism detected in some myotonic dystrophy patients. The clinical importance of maternal IgG for the defense of the neonate is well established. Another clinical area to which FcRn is relevant is that of monoclonal antibody therapeutics, where slow catabolism of IgG is generally desirable. Knowledge of the mechanism of FcRn function will contribute to a rational basis for clinical intervention in complications of maternofetal antibody transmission, and for manipulation of the half-lives of therapeutic antibodies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MECHANISMS OF GENETIC INSTABILITES OF TRIPLET REPEATS Principal Investigator & Institution: Wells, Robert D.; Director; Center for Genome Research; Texas A&M University Health Science Ctr College Station, Tx 778433578 Timing: Fiscal Year 2002; Project Start 01-JUN-2001; Project End 31-MAY-2006 Summary: (Applicant's abstract): Genetic instabilities (expansion and deletions of simple repeating sequences) are important in the life cycles of both prokaryotic and eukaryotic cells. This fundamental mechanism of mutagenesis has been found in mycoplasma, bacteria, yeast, mammalian cells, and in humans. In lower organisms, these genetic polymorphisms are the basis for phase variations which control the expression of genes. In humans, the expansions and deletions of simple repeating sequences are closely tied to the etiologies of cancers as well as hereditary neurological diseases. Prior work has revealed that expansions are mediated by DNA replication and repair by the slippage of the complementary strands of the repeats to form hairpin loop structures with differing relative stabilities. The principal investigator has recently demonstrated that recombination is a powerful mechanism for generating large expansions. To the extent that this work can be extrapolated to human diseases, recombination may be an important mechanism for the large expansions found in fragile X syndrome, myotonic dystrophy, and SCA8. The first Specific Aim is to elucidate the mechanisms of genetic recombination which mediate the triplet repeat sequence (TRS) expansions. Specific Aim 2 will evaluate the role of recombinational repair of double strand breaks in genetic instabilities. The third Specific Aim is to establish a genetic assay for determining the recombination frequency. Specific Aim 4 will investigate tandem duplication-based instabilities in vivo in recA- cells. In summary, the principal investigator will investigate the molecular mechanisms (replication, recombination, repair) that cause genetic instabilities in simple repeat sequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR ANALYSIS OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Bhagwati, Satyakam; Neurology; Suny Downstate Medical Center 450 Clarkson Ave New York, Ny 11203 Timing: Fiscal Year 2002; Project Start 01-DEC-1997; Project End 31-MAY-2004

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Summary: (Adapted from Applicant's Abstract): The molecular basis of several human diseases has recently been found to be expansions of simple trinucleotide repeat DNA sequences. In this proposal, we focus on the neurological disease myotonic dystrophy (DM), which is caused by a (CTG)n expansion in the 3'untranslated (3'UTR) region of the DM protein kinase (DMPK) gene. The long term objectives of this proposal are to understand the cellular consequences of the CTG repeat expansion and the pathogenesis of myotonic dystrophy. The Specific Aims of this proposal are to: 1) develop and analyze a transgenic moused model for myotonic dystrophy; and 2) analyze proteins which bind to the repeat expansion in genomic DNA (CTG)n or RNA (CUG)n. The health relatedness of this project are that it will provide a better understanding of the pathogenesis of one of the commonest muscular dystrophies, myotonic dystrophy, and about diseases caused by triplet repeat expansions in general. It will also provide an animal model for DM allowing different therapies to be tested in the future. The research design and methods we plan to use are: 1) Gene targeting by homologous recombination in embryonic stem cells to target a (CTG)n repeat expansion to the 3' UTR of the mouse DMPK gene. Transgenic mice harboring and expanded CTG repeat in the DMPK gene will be analyzed for repeat stability and the pathophysiological features of DM. 2) We have previously identified, purified and partially sequenced two proteins which bind to single stranded DNA (CTG)n and RNA (CUG)n repeats. The genes encoding these proteins will be cloned and sequenced to study gene structure and chromosomal localization. Antibodies to these repeat binding proteins will be used to study the expression pattern of these proteins in normal and DM tissues and recombinant proteins will be used to study their RNA binding properties. This approach is designed to explore the function of these CTG/CUG repeat binding proteins and their possible role in the pathogenesis of DM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR GENETIC CHARACTERIZATION OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Krahe, Ralf; Molecular Genetics; University of Texas Md Anderson Can Ctr Cancer Center Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 24-SEP-2001; Project End 30-JUN-2006 Summary: (provided by applicant): The myotonic dystrophies (DM) are now collectively recognized as a clinically and genetically heterogeneous group of neuromuscular disorders, characterized by autosomal dominant inheritance, muscular dystrophy, myotonia, and multi-system involvement. Recent work by others and us indicates at least two more DM loci in addition to DM1, the (CTG)n expansion in chromosome 19q13.3. Multiple families with clinically variable presentation from predominantly distal to exclusively proximal muscle involvement show linkage to a locus in 3q21, designated DM2. However, several families with similar presentations have been excluded from this region. Thus, there is at least a third DM locus (DM3), which has yet to be mapped. The long-term goal of this proposal is the identification of DM2 in the families mapping to 3q21, and the mapping and cloning of the remaining gene(s) in the DM2-unlinked families. The characterization of the underlying mutations will be the basis for phenotype/genotype correlations. Three specific aims are proposed: (1) to clone and characterize DM2 in 3q21; (2) to clone and characterize the gene(s) in DM2-unlinked/DM3 families, and (3) to globally expression profile DM muscle with DNA microarrays. Collaborating with clinical groups from the USA and Europe, we have ascertained 57 families with clinically similar phenotypes, which are negative for the DM1 (CTG)n expansion or any of the other known myotonia loci. Ten of 21 families

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suitable for linkage analysis show linkage to 3q21, while 11 are unlinked. We have substantially narrowed the DM2 critical region, generated a physical transcript map and started to examine functional-positional candidate genes, using various mutation detection assays. For DM3 we propose the same strategy of positional cloning that has proved successful for DM2. Genome-wide expression profiling of DM muscle will identify dysregulated genes and provide valuable functional clues about potential candidate genes and complex cellular candidate pathways, the overall pathophysiology of DM, and potential molecular therapeutic targets. The identification of these novel genes and the characterization of their mutations and pathophysiological role(s) are the first step in developing potential therapies for patients suffering from these inherited myotonic dystrophies. Moreover, as the cellular pathologies among the different myotonic dystrophies show considerable overlap, the identification of the genes underlying DM2 and DM3 and their corresponding expression profiles may also provide valuable insights into the pathology of DM1, which continues to elude researchers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Timchenko, Lubov T.; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-SEP-1997; Project End 31-AUG-2007 Summary: (provided by applicant): Myotonic dystrophy (DM) is a neuro-muscular disease with a complex inheritance and an extremely complex molecular pathophysiology. We have suggested that unstable CTG repeats responsible for DM cause the disease at the RNA level via recruitment of specific RNA-binding proteins. We identified a CUG RNA-binding protein, CUGBP 1, and showed that this protein is recruited by CUG repeats into heavy RNA-protein complexes in cardiac tissue from DM patients. In order to investigate the role of CUGBP 1 in skeletal muscle differentiation, we generated primary skeletal muscle lines from DM patients and showed that a significant portion of DM cells fail to exit cell cycle during differentiation and that DM cells are able to proliferate. The failure of DM cells to differentiate is accompanying with a failure to accumulate CUGBP1 in cytoplasm. Our data show that CUGBP1 regulates translation of several mRNAs, including mRNA coding for an inhibitor of cell cycle, p21. p21 plays a key role in the differentiation of skeletal muscle. The major hypothesis of this application is that, under normal conditions, 1) CUGBP1 regulates cell cycle withdrawal in skeletal muscle via induction of p21 translation. 2) In DM skeletal muscle cells, expansion of CUG repeats within the mutant DMPK mRNA recruits CUGBP1 leading to the trapping CUGBP1 in nuclei and to inhibition of its cytoplasmic function: induction of p21. 3) The reduction of p21 in DM muscle cells results in a delay in exit from the cell cycle during muscle differentiation. Specific Aim I will define molecular mechanisms by which CUGBP1 is trapped in nuclei of DM differentiated cells. Specific Aim II examines the role of cytoplasmic CUGBP1 in p21-dependent regulation of skeletal muscle differentiation. Myoblast cell cycle progression and exit from the cell cycle will be examined in DM patients and in cell cultures with reduced levels of CUGBP 1. Specific Aim III will examine whether an increase of CUGBP 1 in nuclei of DM cells affects skeletal muscle differentiation. Myoblast cell cycle withdrawal and efficiency of myoblast fusion will be examined in cells derived from transgenic mice overexpressing CUGBP1. p21-dependent and p21-independent pathways will be examined. We will test whether other CUG repeats binding proteins are also affected in DM skeletal muscle.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR MECHANISMS OF THE MYOTONIC DYSTROPHY MUTATION Principal Investigator & Institution: Mahadevan, Mani S.; Pathology; University of Virginia Charlottesville Box 400195 Charlottesville, Va 22904 Timing: Fiscal Year 2002; Project Start 09-APR-1999; Project End 31-MAR-2004 Summary: Myotonic dystrophy (DM) is the most common inherited neuromuscular disorder in adults with a global incidence of 1 per 8000. The DM mutation was found to be an expansion of an unstable CTG triplet repeat in the 3' untranslated region (3'UTR) of a gene encoding a serine-threonine protein kinase (DMPK). However, the mechanism by which it causes disease is unknown. We and others have found that the mutant DMPK mRNA is trapped within the nucleus of DM cells and forms distinct, stable foci of mRNA. In addition, we have demonstrated that the mutant DMPK 3'UTR mRNAhas significant negative effects on gene expression. Furthermore, we have identified that expression of the mutant DMPK 3'UTR mRNA in myoblasts causes defects in myoblast fusion and differentiation, demonstrating that this RNA work in trans on the expression of other transcripts, and causes a disease relevant cellular phenotype. This study is directed at understanding the molecular biology of DM by addressing the hypothesis that DM is a paradigm for RNA mediated disease processes. The proposed experiments will be aimed at assessing and determining the effect of the DMPK messenger RNA (mRNA) on gene expression. The effects of the normal and mutant DMPK 3'UTR mRNA will be studied initially at the cellular level, secondly from a biochemical persepective and finally in vivo through the creation of a transgenic murine model. The hypothesis to be tested by this proposal is that: Myotonic dystrophy is a disease in which dysregulation of RNA metabolism mediated by the mutant DMPK mRNA contributes to the pathophysiology of DM. The specific aims of this proposal are directed at: 1) studying the effects of the DM mutation in a cell culture model, 2) identifying genes whose expression is altered by the presence of the mutant DMPK 3'UTR mRNA and 3) the establishment of a murine model to study the in vivo effects of the DM mutation on RNA metabolism and their contribution to DM pathogenesis. The long term objectives of this proposal are to understand the molecular mechanisms by which the DM mutation functions in order to provide insight into the pathophysiology of DM, to allow for the development of appropriate animal models, and to eventually lead to a more rational approach to therapeutic intervention in DM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR MECHANISMS WHEREBY CTG EXPANSION RESULTS IN DM Principal Investigator & Institution: Reddy, Sita; Biochem and Molecular Biology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, Ca 90033 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the Investigator's Abstract): Expansion of a CTG repeat sequence located in a gene rich region on chromosome 19ql3.3 results in the neuromuscular disorder, myotonic dystrophy (DM). As the expansion is not found in the coding region of a gene the mechanistic basis of DM has remained a puzzle. Two current models hypothesize that CTG expansion may result in deleterious cis-effects that alter gene transcription in its vicinity and/or have toxic effects that are intrinsic to the repeat sequence. To test these mechanistic models mouse strains encoding large

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CTG expansions have been developed. Transgenic mice in which CTG expansions have been knocked into the dm locus will be used to characterize the phenotypic consequence of the cis effects of CTG expansion and the intrinsic toxicity of the repeat sequences. Mice encoding expansions of 500 and 2000 repeats at the dm locus will be used to test the hypothesis that cis effects that alter gene transcription in the vicinity of the expansion, progressively spread across the chromosome to boundaries that are dictated by the size of the repeat tract. Toxic effects of the CTG/CUG repeat expansion will be independently characterized in mice encoding expanded CTG tracts integrated at random loci in the genome under the transcriptional control of the human beta actin promoter. We will test the hypothesis that an increased frequency of double-strand breaks in the CTG repeat tracts or pre-mRNA splicing abnormalities resulting from the titration of the splicing factor CUG-BP by the expanded CUG repeats are the molecular mechanism whereby expanded CTG/CUG repeats result in DM pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR PATHOGENESIS OF MYOTONIC DYSTROPHY Principal Investigator & Institution: Cooper, Thomas; Associate Professor; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2004; Project Start 08-FEB-1999; Project End 28-FEB-2009 Summary: (provided by applicant): Myotonic dystrophy (DM) is the most common form of adult onset muscular dystrophy affecting 1 in 8500 people worldwide. It is dominantly inherited and affects multiple organ systems. Causative mutations are expanded tri-(CTG) and tetra-(CCTG) nucleotide repeats in transcribed but nontranslated genomic regions. A major pathogenic mechanism of DM involves a toxic RNA gain-of-function caused by expression of RNA transcripts from the expanded alleles. The goal in this proposal is to determine the molecular mechanism by which RNA containing the expanded repeats causes progressive skeletal muscle dystrophy and cardiac arrhythmias, the predominant causes of mortality and morbidity. In the previous funding period we demonstrated that the pathogenic mechanism involves misregulation of alternative splicing and we identified target genes responsible for specific symptoms. We also found, that these targets are regulated antagonistically by two families of RNA binding proteins both identified previously based on CUG RNA binding activity. We will define the mechanism by which expanded CUG RNA induces pathogenesis with specific emphasis on the roles of individual members of these two protein families. First, while it is clear that CUG repeat RNA is pathogenic, the specific form of the RNA required for pathogenicity is unknown. We will use an established assay to define the sequence, protein binding, and structural features of RNA required for induction of splice-misregulation in trans. Proteins whose direct interactions with the RNA correlate with aberrant RNA processing will be identified. Second, genes whose mis-regulation contributes to myopathy and arrhythmias will be identified using novel biochemical and subtractive approaches. Third, stable cell lines inducibly expressing expanded CUG RNA will be used to characterize the distribution and metabolism of toxic RNA and the consequences on the expression of the RNA binding proteins that are relevant to cell toxicity. Fourth, we will develop versatile lines of transgenic mice using a Cre/LoxP strategy to induce high levels of expanded CUG RNA in specific tissues and in early development. These studies will provide cellular and mouse models to define altered regulatory pathways and the genes affected by this novel disease mechanism. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR PATHOPHYSIOLOGY OF FACIOSCAPULOHUMERAL MUSCUL* Principal Investigator & Institution: Chen, Yi-Wen; Children's Research Institute Washington, D.C., Dc 20010 Timing: Fiscal Year 2002; Project Start 28-SEP-2001; Project End 31-MAY-2004 Summary: (provided by applicant): Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited muscle diseases following Duchenne muscular dystrophy and myotonic dystrophy. The disorder is autosomal dominant with nearly complete penetrance (95%) by age 20. Severity of muscle involvement in FSHD is extremely variable, ranging from elderly individuals with mild facial weakness to wheelchair bound children. Besides variability between individual patients, FSHD patients often show enigmatic asymmetry of muscle involvement. This disease feature permits a novel experimental design, where progression of the disease can be studied within a single patient at a single time point. Previous studies showed a statistically significant correlation between severity of clinical presentation and the deletion of D4Z4 repeats on chromosome 4q35 in patients with FSHD. Current hypotheses center on a position effect of telomeric sequences on genes in or near the deletion site, however the molecular mechanisms underlying this disease are far from clear. In our study, we hypothesize that FSHD patient muscle shows a disease-specific expression profile, relative to other muscle disease (Duchenne muscular dystrophy, alpha-sarcoglycan deficiency, juvenile dermatomyositis, and dysferlin deficiency). In addition, we hypothesize that one can identify a subset of the FSHD-specific genes will be shown to correlate with progression of-muscle involvement in FSHD muscle by comparing expression changes correlated with clinically-affected vs. unaffected muscles within single dystrophy patients. In our preliminary data, we have defined an FSHD-specific set of 29 genes that are candidates for primary involvement of disease pathogenesis by using the HuGeneFL array (-6,000 full length genes). In this proposal, we plan to broaden the number of genes studied, so that a genome-wide set of genes implicated in the primary etiology can be defined. Specifically, we will extend our truly promising preliminary data to over 60,000 genes and EST sequences included on the Human genome U95A, B, C, D, E stock chips, as well as the > 2,000 human muscle ESTs on our custom-produced MuscleChip. In addition, a custom glass slide array consisting of - 200 genes and ESTs from 4q35 and lOq26 will be used to identify FSHD region specific alterations in gene expression. All FHSD-specific ESTs identified will be characterized in detail. Further studies will likely include the delineation of a complete picture of the pathophysiology of FSHD, as well as identification of functional SNPs in the refined gene list that correlate with disease severity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MOLECULAR PATHWAY TO CARDIAC CONDUCTION DEFECTS Principal Investigator & Institution: Housman, David E.; Professor; Massachusetts Institute of Technology Room E19-750 Cambridge, Ma 02139 Timing: Fiscal Year 2002 Summary: The overall goal of Project IV (Housman) is to utilize the DMPK deficient mouse to analyze the genetic interactions that lead to cardiac conduction defects and heart block in this model system. The DMPK knockout mouse was developed to model characteristics of myotonic dystrophy, an inherited disorder in which cardiac conduction defects in the AV node and infra-Hisian and supra-Hisian tissue are a primary cause of premature death. The DMPK knockout mouse model strikingly

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resembles this pattern of cardiac conduct defect. Mice with absence of function for DMPK show normal cardiac conduction during the first two months of life. Between two and five months these animals develop lengthening of PR interval, lengthening of HIV interval and secondary and tertiary heart block. To define the molecular pathways that lead to this pathological outcome, we will carry out focused efforts to 1) determine the substrates for the protein kinase activity of DMPK 2) resolve the relative roles of two alternative splices splice forms of DMPK that show differential subcellular localization and 3) investigate the role of novel genes identified by transcriptional profiling, proteomic analysis and genetic modifier screens. We will develop a baseline for proteomic analysis of mouse cardiac development and pathology that will be applicable to other Projects in this program. We will also develop for executing mouse modifier gene mapping that will support the efforts of other Projects in this program in identifying gene interactions through genetic modifier mapping. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOUSE MUSCLEBLIND MODEL FOR MYOTONIC DYSTROPHY Principal Investigator & Institution: Swanson, Maurice S.; Professor; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2008 Summary: The myotonic dystrophies (DM1 and DM2), which are the most common form of adult-onset muscular dystrophy, are autosomal dominant diseases with similar clinical presentations. Remarkably, DM1 and DM2 are caused by unstable microsatellite expansions in the untranslated regions of two different genes, DMPK and ZNF9. To explain how these non-coding expansion mutations lead to dominantly inherited neuromuscular disorders, we have proposed a toxic RNA model for the myotonic dystrophies. Transcription of the mutant DM1 (CTG)n and DM2 (CCTG)n alleles leads to the production of unusual RNA transcripts with (CUG)n and (CCUG)n repeat expansions. These expansions fold into stable double-stranded (ds) RNA structures that recruit and then sequester a family of dsRNA-binding factors, the muscleblind proteins. Because this toxic RNA model suggests that DM1 and DM2 diseases are due to loss of muscleblind protein function, we have derived muscleblind 1 (Mbnl1) knockout mice. This proposal is designed to test our working hypothesis that Mbnl1-/- knockout mice will be a useful model to examine underlying molecular mechanisms involved in myotonic dystrophy disease pathogenesis. First, we will characterize the Mbnl1-/muscle phenotype and test the hypothesis that Mbnl1 is required for proper alternative splicing and function of the chloride channel CIC-1. Deficiency of this ion channel has been recently implicated as the cause of DM1- and DM2- associated myotonia. The stoichiometric relationship between toxic RNA and binding protein will be examined by breeding Mbnll knockout mice with lines of transgenic mice that express (CUG)n RNA at different levels. Second, the possibility that muscleblind proteins influence CIC-1 chloride channel levels by interacting with alternative splicing, and/or other, factors will be examined. Third, the hypothesis that the myotonia phenotype can berescued using recombinant adeno-associated virus mediated expression of wild type adult CIC-1 will be tested. Finally, we will investigate if additional disease-associated phenotypes result from deletion of the entire Mbnl1 gene, from tissue-specific Mbnl1 expression or from combinatorial loss of all three muscleblind (Mbnl1, Mbnl2/Mbnll, Mbnl3/Mblx) genes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MUSCULAR DYSTROPHY COOPERATIVE RESEARCH CENTER Principal Investigator & Institution: Chamberlain, Jeffrey S.; Professor; Neurology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2008 Summary: This MDCRC application is designed to advance our abilities to treat the muscular dystrophies by capitalizing on the breadth and depth of expertise at our collaborating institutions in the fields of neuromuscular disease research and patient care, molecular genetics, immunology, and gene therapy. The participating researchers include scientists and clinicians from the University of Washington Medical Center, Children's Hospital and Regional Medical Center, Fred Hutchinson Cancer Research Center, and the VA Medical Center, Seattle. Our goals are to provide an interactive environment that will advance knowledge of and treatments for the muscular dystrophies by promoting collaborations, providing shared resources, advancing basic research, stimulating translational research, fostering outreach activities, developing greater patient awareness of basic and clinical research and enabling their participation in clinical trials, and by facilitating the development gene therapy for the muscular dystrophies. Our Center is composed of four research projects and three Core laboratories, and includes a membership of more than 30 faculty members in the Seattle area with interests in neuromuscular disease research. The director and codirector are J Chamberlain and S Tapscott, researchers with a long history of genetic and clinical studies of the muscular dystrophies. Project 1 (J Chamberlain, S Tapscott and S Froehner) will conduct pre-clinical studies in dystrophic mice that lead to a phase I clinical tdal of gene therapy for Duchenne muscular dystrophy (DMD). Project2 (M-T Little and S Tapscott) will study the canine model for DMD to address pre-clinical issues related to DMD therapy by emphasizing immunological, safety and allometdc issues important for the evelopment of therapies for DMD. Project 3 (S Hauschka) explores issues important for regulating gene expression vectors in muscles of humans, mice and dogs, and will develop animal and cell culture models for human muscle gene transfer. Project 4 (S. Tapscott) will study abnormal gene expression in cells from individuals with myotonic dystrophy, and will explore the clinical significance of methylation at the DM1 locus in adult onset myotonic dystrophy. Core A (Chamberlain) is an administrative core to coordinate and organize collaborative and interactive activities within and outside of our center. Core B (Chamberlain, J Allen) is a viral vector core and a scientific research resource core that will facilitate the availability of research and clinical grade gene transfer vectors for basic research and the development of gene therapies for the muscular dystrophies. Finally, Core C (T Bird) is a genetic counseling core for patients and families with muscular dystrophy that will also allow increased participation of patients in studies of a variety of types of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MYOCARDIAL MYOTONIC DYSTOPHY PROTEIN KINASE FUNCTION Principal Investigator & Institution: Perryman, M Benjamin.; Director; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: (the applicant's description verbatim): The overall goal of this research project is to identify the functional role of human myotonic dystrophy protein kinase (DMPK) in myocardium. DMPK was the first identified member of a novel family of

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multi-domain serine-theronine protein kinases defined by a unique kinase core and common non-catalytic domains. Physiological substrates and functions for most members of this kinase family are unknown. DMPK was originally identified when a CTG triplet repeat sequence located in the 3' untranslated region of the DMPK gene was identified and shown to be expanded in patients with myotonic dystrophy (DM). DM is an autosomal dominant myopathy with pleiotropic effects including skeletal muscle weakness and wasting, a cardiomyopathy with cardiac conduction abnormalities and myocardial dysfunction, frontal baldness, and cataracts. The pathophysiology of DM is not understood, and a number of mechanisms-including reduced DMPK expression, RNA splicing defects, and reduced expression of a homeobox gene-have been postulated to explain this complex phenotype. DMPK mRNA and protein expression is greater in myocardium than in any other tissue type implying the presence of a previously unknown protein kinase mediated signal transduction pathway in myocardium. We hypothesize that DMPK is a multifunctional protein kinase and is a component of a previously uncharacterized myocardial and skeletal muscle signal transduction pathway. Alterations in the DMPK signaling pathway are likely to be responsible for at least a portion if not all of the pathophysiology of myotonic dystrophy. This hypothesis cannot be directly tested without a better understanding of fundamental properties of the kinase including DMPK enzymatic activity, domain structure and interacting proteins. We will use biochemical analysis and molecular biology techniques to characterize DMPK enzymatic activity and autophosphorylation, identify potential physiologic substrates, define DMPK domain function, determine the effect of DMPK proteolytic processing on enzyme function and localization, and determine the functional relationship of DMPK to other members of this kinase family. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYOTONIC DYSTROPHY AND RELATED DISORDERS Principal Investigator & Institution: Day, John W.; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070 Timing: Fiscal Year 2002 Summary: A previously undefined autosomal dominant muscle disease has been identified in a five generation family (MN1). Although this family has the clinical features associated with myotonic dystrophy (DM), affected individuals do not have the CTG expansion associated with DM, nor is the disease locus linked to the DM region of chromosome 19. Linkage to other genetic loci that cause myotonia have been excluded. We propose to genetically map the MN1 locus, first by performing a genome screen and then by developing a high resolution genetic map for the MN1 region. The identification of a second locus for DM will facilitate the identification of additional families with the MN1 form of DM and will be a first step toward identifying the MN1 gene. Because the MN1 disorder causes the same broad range of clinical features as classic DM, the eventual isolation and characterization of the gene(s) affected will provide insights into the pathology of both DM and the disease afflicting the MN1 family. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MYOTONIC DYSTROPHY LOCUS CONTROL Principal Investigator & Institution: Tapscott, Stephen J.; Professor; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2002; Project Start 01-SEP-1998; Project End 31-AUG-2003

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Summary: Myotonic dystrophy (DM) is caused by the expansion of a CTG repeat. The repeat is in the 3' end of the dystrophia myotonia protein kinase gene (DMPK) and immediately 5" of the dystrophia myotonia associated homeobox protein (DMAHP) gene. It is still unknown whether the altered expression of either of these genes contributes to the DM phenotype. While a large amount of work from other labs has demonstrated that the CTG expansion affects the processing of the DMPK transcript, work in my lab has demonstrated that expression of the adjacent DMAHP gene is suppressed by the expanded repeat. Th investigator's have demonstrated that a welldefined hypersensitive site is positioned between the repeat and the promoter of the DMAHP gene. They have shown that the hypersensitive site contains transcriptional enhancer elements and the activity of these elements correlate with expression of the DMAHP gene suggesting that expansion of the repeat both eliminates the hypersensitive sit and suppresses expression of the adjacent DMAHP gene. These data support the broad hypothesis that the hypersensitive site is critical for the normal regulation of gene expression at the myotonic dystrophy locus, and that suppression of factor access to this region contributes to the myotonic dystrophy phenotype. The broad goals of this application are to characterize the regulatory and structural elements at the myotonic dystrophy locus and determine whether they have a role in the pathogenesis of myotonic dystrophy. The specific aims of the application are to (1) characterize the regulatory elements of hypersensitive site enhancer and DMAHP promoter; (2) characterize the elements at the locus that establish nucleosome phasing and maintain the hypersensitive site; (3) determine whether inactivation of the DMAHP gene or the hypersensitive site enhancer contributes to the phenotype of myotonic dystrophy. The significance of the proposal is that this application will characterize the elements that regulate gene expression at the myotonic dystophy locus and determine the role of these elements in the pathophysiology of myotonic dystrophy, ultimately leading to the rational design of therapies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EXPRESSION

NUCLEAR

AND

GENOMIC

ORGANIZATION

OF

GENE

Principal Investigator & Institution: Lawrence, Jeanne B.; Associate Professor; Cell Biology; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, Ma 01655 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): Research proposed is directed to understanding the interplay between complex nuclear structure, gene expression, and genomic organization. It is increasingly recognized that the mammalian nucleus is more complex than earlier envisioned, with a number of distinct intranuclear compartments or "domains" whose functions are yet to be uncovered. Our focus is on the functional relationship of specific gone loci and mRNAs (or pre-mRNAs) with SC35 domains, regions rich in poly (A) RNA and mRNA metabolic factors. A substantial subset of active protein-coding genes position at the immediate periphery of these domains. This positioning is correlated with cell-type specific gene regulation. In contrast, some inactive genes localize to a heterochromatic compartment. In addition, Cajal Bodies associate with snRNA and histone genes while PML domains are known to associate with DNA viruses. Hence, genes are expressed (or repressed) in different nuclear environments. This concept has far-reaching but unexplored implications for gone expression. In Aim 1 we will investigate what sequences or properties of a gene locus determine association with SC35 domains, which we suggest may be reciprocally

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Myotonic Dystrophy

related to localization in the heterochromatic compartment. The cause and effect relationships between domain association and gene transcription, and the possible influence of "nuclear neighborhood" will be examined. Aim 2 investigates the hypothesis that passage of some largely spliced mRNAs through an SC35 domain is a previously unrecognized step in early transport from the gene, and can be blocked in conditions that perturb nuclear trafficking. Strategies include the analysis of specific human disease mutations that block transport of mutant transcripts, applied specifically to nuclear RNAs carrying triplet repeats in myotonic dystrophy. Aim 3 proposes development of a novel approach that couples bioinformatic analysis of genomic sequence with molecular cytology to investigate potential inter-relationships between chromosomal linkage, gene expression, and nuclear compartments. Hypotheses tested have potential to elucidate the functional evolution of the karyotype and such features as cytogenetic bands and conserved gene clusters, which may associate with distinct intranuclear compartments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF ALTERNATIVE SPLICING IN MUSCLE BY ETR-3 Principal Investigator & Institution: Ladd, Andrea N.; Pathology; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2002; Project Start 01-AUG-2002 Summary: The goal of this project is to understand the mechanisms that regulate alternative splicing during striated muscle development. Cardiac troponin T (cTNT) undergoes developmentally regulated alternative slicing in striated muscle, and is a useful model for cell-specific splicing regulation. cTNT pre-mRNAs contain musclespecific splicing enhancers (MSEs), intronic elements that are required for the enhanced alternative exon inclusion that is observed in embryonic striated muscle. ETR-3, a member of a conserved family of RNA-binding proteins, binds MSEs and promotes MSE-dependent exon inclusion. ETR-3 is induced during skeletal muscle differentiation and undergoes an isoform transition during heart development. Both of these changes correlate with regulated switches in cTNT splicing. These results strongly suggest that ETR-3 is a major regulator of alternative splicing in striated muscle development. To determine the role of ETR-3 in muscle-specific alternative splicing, I will: (i) Characterize ETR-3 as a positive regulator of alternative splicing during skeletal muscle differentiation, (ii) Determine the significance of the ETR-3 isoform transition during heart development, and (iii) Determine the role of ETR-3 in coordinated regulation of alternative splicing during striated muscle development. ETR-3 is 78% identical to CUGBP, which is proposed to mediate pathogenesis of myotonic dystrophy, an autosomal dominant genetic disorder caused by an expansion of unstable CTG repeats in the 3' UTR of the DMPK gene. Expanded DMPK transcripts accumulate in the nucleus, and are thought to affect post-transcriptional processing of other genes by disrupting function of CUG-BP. Our results suggest that ETR-3 is an equally likely candidate for mediating a trans-dominant effect in DM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DYSTROPHIES

RNA-MEDIATED

MECHANISMS

IN

THE

MYOTONIC

Principal Investigator & Institution: Thornton, Charles A.; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006

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Summary: (provided by applicant): The myotonic dystrophies [DM], including myotonic dystrophy type 1 [DM 1] and myotonic dystrophy type 2 [DM2], are dominantly inherited, multisystem diseases that share the major disease manifestations of myotonia, wasting ad weakness. DM1 is caused by an unstable CTG repeat expansion on chromosome 19q13.3 and DM2 by an unstable CCTG repeat expansion 3q21. The cause for the skeletal muscle findings in these disorders remains a mystery. We hypothesize that they result from toxic effect of mutant RNA, a RNA mediated gain of function. Support for our hypothesis comes from studies in a mouse model of DM1. The muscles of the mice show a focal accumulation of expanded CUG repeats in the nucleus. These nuclear foci closely resemble the RNA foci of expanded CUG repeats in DM1 and expanded CCUG repeats in DM2. Expression of the expanded CUG repeat in the transgenic model causes myotonia, like that seen in DM1 and DM2. We have obtained evidence that myotonia in the transgenic model results from aberrant splicing of the chloride channel 1(CIC-1) pre-mRNA, and consequent loss of CIC-1 protein and chloride conductance from the muscle membrane. We hypothesize that a similar RNAmediated disturbance of RNA processing underlines myotonia and other disease manifestations in DM1. To test this hypothesis we will evaluate patients with DM1 and DM2, disease controls, and normals using clinical and electromyographic testing, needle muscle biopsy, tissue culture techniques, studies of RNA expression and splicing, immunofluorescence microscopy, and microarray analysis to address four specific aims. These aims are: 1) define the mechanism of myotonia - analyze splicing of CIC1 inDM1 and DM2; 2) determine the extent of mis-splicing (beyond CIC1) in DM1 and DM2; 3) examine the structure/distribution/protein binding characteristics of the nuclear foci containing the expanded repeats in DM1 and DM2; and, 4) assess the expression profile of mRNA inDM1 and DM2. The results of these investigations will shed light on the possibility that RNA gain-of-function represents a fundamental, shared disease mechanism in all forms of myotonic dystrophy. The findings may also help to explain the common clinical manifestations that occur in DM1, DM2, and other myotonic dystrophy like disorders. Ultimately our results may improve our understanding of the pathophysiology of DM and guide us toward the development of new approaches to treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RNA-PROTEIN INTERACTIONS IN THE NERVOUS SYSTEM Principal Investigator & Institution: Jensen, Kirk B.; Lab/Molecular Neurooncology; Rockefeller University New York, Ny 100216399 Timing: Fiscal Year 2002; Project Start 16-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The exploration of the role played by RNA binding proteins in the nervous system continues to be an exciting and productive area of research. Neuronal RNA binding proteins function as alternative splicing factors, regulate mRNA stability and protein translation, and can localize mRNA to dendrites; thus these proteins are key regulators of gene regulation in neurons. RNA binding proteins in the nervous system also have important implications for human health: the fragile X syndrome, spinal muscular atrophy, spinocerebellar ataxia 8 and myotonic dystrophy all involve disregulation of RNA-protein interactions in neurons. The major obstacle in the further understanding of how neuronal RNA binding proteins function has been the identification of RNA substrates. The goal of this proposal is to further define the function of the Nova and Hu families of neuron-specific RNA binding proteins, and central to this aim is the identification of those RNA molecules that bind to Nova and Hu in vivo. Here, we describe new methodology we have developed to

24

Myotonic Dystrophy

systematically and comprehensively identify neuronal RNAs bound by the Nova and Hu proteins. Furthermore, specific hypotheses regarding the interaction of Nova and Hu with these RNAs will be biochemically examined in vitro and in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: STABILITY & FRAGILITY OF TRINUCLEOTIDE REPEATS IN YEAST Principal Investigator & Institution: Freudenreich, Catherine H.; Assistant Professor; Biology; Tufts University Medford Boston Ave Medford, Ma 02155 Timing: Fiscal Year 2002; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: (Verbatim from the applicant's abstract): Expansion of trinucleotide repeat (TNR) sequences is the causative mutation for a number of hereditary diseases, including myotonic dystrophy, the most common dystrophy in adults, Fragile X syndrome, the most common form of inherited mental retardation, and neurodegenerative diseases such as Huntington's and the spinocerebellar ataxias. The mechanism of TNR instability is interesting both for understanding the etiology and inheritance of the triplet repeat diseases, and for a basic understanding of genome stability in humans. In addition, expanded CGG/CCG and CTGICAG sequences are sites of chromosome fragility, areas prone to breakage in vivo. Chromosome breakage is implicated in the generation of translocations and deletions found in many types of cancer. The aim of this proposal is to elucidate the mechanisms involved in TNR instability and fragility, and determine how these two unusual characteristics are interrelated using Saccharomyces cerevisiae. A novel genetic assay has been developed that produces a selectable phenotype when a TNR tract expands or breaks. This assay will be used to screen for proteins whose over-expression influences TNR expansion or fragility. The proteins found to influence TNRs will be characterized to determine both their normal cellular functions and their influence on repeat maintenance. In addition, the hypothesis that TNR expansions occur by aberrant lagging strand replication will be tested by analyzing tract stability (by PCR) and fragility (by genetic and physical analysis) in specific yeast replication mutants. The role of the G2IM checkpoint in detecting TNR tract damage and preventing chromosome breakage will be investigated by comparing rates of TNR tract breakage in wild-type and cheokpoint-defective cells. Lastly, these analyses will be extended to other types of minisatellite sequences that act as fragile sites in human cells. The proposed experiments are designed to elucidate not only how simple repeats expand to cause human disease, but also the consequences of and cellular response to expanded tracts, with the goal of understanding how genomic instability can affect human health. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: STRUCTURE AND FUNCTION OF CTCF: MOUSE MODEL STUDIES Principal Investigator & Institution: Filippova, Galina N.; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2003; Project Start 05-JUN-1996; Project End 31-AUG-2008 Summary: (provided by applicant): CTCF is a highly conserved 11 Zn finger (ZF) transcription factor and insulator protein. CTCF is involved in multiple aspects of gene regulation including promoter activation and repression, hormone-responsive gene silencing, methylation-dependent chromatin insulation, and genomic imprinting. Moreover, our recent discovery of a methylationsensitive CTCF insulator at the DM1 locus that might be responsible for the severe phenotype of Congenital Myotonic Dystrophy (Filippova et al.,2001), and our preliminary data on the role of CTCF

Studies

25

insulators in X chromosome inactivation strongly suggest a link between CTCF and epigenetic regulation in development. Several findings also point to a role for CTCF as a tumor suppressor gene in both cancer epigenetics and genetics. Aberrant methylation of certain CTCF target sites, that is predicted to prevent CTCF-binding, has been demonstrated in a number of tumors. CTCF maps to human chromosome 16q22, within a region that displays frequent cancer-associated deletions (Filippova et al.,1998). We have observed somatic missense mutations within the CTCF 11ZF DNA-binding domain in breast, prostate and Wilms' tumors (Filippova et al.,2002). CTCF +/- mice exhibit enhanced tumor development in multiple tissues. Homozygous deletion of the CTCF results in early embryonic lethality, whereas the CTCF heterozygous mice exhibit decreased embryonic survival. Our broad and longterm hypothesis is that certain functions of CTCF are essential in early development and maintaining cell viability, whereas its other functions, when lost, result in the malignant phenotype. To test this hypothesis our specific aims will: Extend our studies on the role of CTCF in tumorigenesis (Aim 1) and early embryonic development (Aim 2). We will determine what genetic and epigenetic mechanisms are involved in CTCF haploinsufficiency. And finally (Aim 3), we will use the Cre-loxP system to generate a conditional CTCF mutant allele, that in combination with various tissue-specific Cre transgenic mice will allow us to test the hypothesis that complete loss of CTCF function leads to cell death in both normal and/or malignant cells, whereas loss of one CTCF allele in somatic tissue predisposes to tumor development. We will also generate knock-in mice harboring CTCF Zn finger point mutations that we have observed in human tumors to determine the functional significance of such mutated alleles in tumor predisposition. The significance of this proposal is that identifying the mechanisms of the CTCF haploinsufficiency will provide new insight into the broad spectrum of clinical human cancer phenotypes associated with LOH at 16q22.1 where CTCF maps. The healthrelatedness is that the identified mechanisms can be targeted for both cancer prevention and therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TRIPLET REPEAT INSTABILITY IN HUMAN TISSUE CULTURE CELLS Principal Investigator & Institution: Farrell, Brian T.; Eppley Institute for Research in Cancer & Allied Diseases; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 10-APR-2003; Project End 09-APR-2008 Summary: (provided by applicant): Trinucleotide repeat (TNR) expansions cause at least 15 neurodegenerative disorders, including Huntington's disease (HD), Friedreich ataxia, myotonic dystrophy and >90% of inherited spinocerebellar ataxias (SCAs). While these diseases are devastating and relentlessly fatal, they show several fascinating genetic properties. First, these mutations occur at a much higher frequency that spontaneous mutations, in some extreme cases with a frequency approaching 100%. Also, TNR expansions are a unique form of mutation in which repeating triplets of nucleotides linearly amplify themselves between successive generations. Amplification of the repeating sequence also produces genetic anticipation, a worsening of disease phenotype of the TNR diseases. I will use a sensitive, specific and portable genetic assay recently optimized in the laboratory of Dr. Robert Lahue to investigate the etiology of TNR instability in human cells. This work will not only enable me to receive expert training in an interesting and important area of basic science research, but will also allow me to advance our understanding of an entire class of fatal neurological diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Myotonic Dystrophy

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “myotonic dystrophy” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for myotonic dystrophy in the PubMed Central database: •

A locus at 19cen-19q13.2 (D19S15) containing three RFLPs linked to myotonic dystrophy (DM) is recognized by probe pJSB6. by Schepens J, Hulsebos T, Smeets H, Coerwinkel M, Brunner H, Ropers HH, Wieringa B.; 1987 Apr 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340933

•

Altered phosphorylation and intracellular distribution of a (CUG) n triplet repeat RNA-binding protein in patients with myotonic dystrophy and in myotonin protein kinase knockout mice. by Roberts R, Timchenko NA, Miller JW, Reddy S, Caskey CT, Swanson MS, Timchenko LT.; 1997 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24290

•

Alternative Splicing Controls Myotonic Dystrophy Protein Kinase Structure, Enzymatic Activity, and Subcellular Localization. by Wansink DG, van Herpen RE, Coerwinkel-Driessen MM, Groenen PJ, Hemmings BA, Wieringa B.; 2003 Aug 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=166319

•

Cbk1p, a protein similar to the human myotonic dystrophy kinase, is essential for normal morphogenesis in Saccharomyces cerevisiae. by Racki WJ, Becam AM, Nasr F, Herbert CJ.; 2000 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=302079

•

Expansion of a CUG trinucleotide repeat in the 3[prime prime or minute] untranslated region of myotonic dystrophy protein kinase transcripts results in nuclear retention of transcripts. by Davis BM, McCurrach ME, Taneja KL, Singer RH, Housman DE.; 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23831

•

Fission yeast orb6, a ser /thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle. by Verde F, Wiley DJ, Nurse P.; 1998 Jun 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=22672

•

Intermolecular and Intramolecular Interactions Regulate Catalytic Activity of Myotonic Dystrophy Kinase-Related Cdc42-Binding Kinase [alpha]. by Tan I, Seow KT, Lim L, Leung T.; 2001 Apr 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=86907

3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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•

Isolation of a polymorphic DNA sequence pJSB11 (D19S16) from the human chromosome 19cen-q13.2 region linked to the myotonic dystrophy (DM) gene. by Schepens J, Smeets H, Hulsebos T, Brunner H, Wieringa B.; 1987 Apr 10; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340932

•

Long CTG Tracts from the Myotonic Dystrophy Gene Induce Deletions and Rearrangements during Recombination at the APRT Locus in CHO Cells. by Meservy JL, Sargent RG, Iyer RR, Chan F, McKenzie GJ, Wells RD, Wilson JH.; 2003 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=153196

•

Mutagenic stress modulates the dynamics of CTG repeat instability associated with myotonic dystrophy type 1. by Pineiro E, Fernandez-Lopez L, Gamez J, Marcos R, Surralles J, Velazquez A.; 2003 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=290266

•

RFLPs at the D19S19 locus of human chromosome 19 linked to myotonic dystrophy (DM). by Roses AD, Pericak-Vance MA, Ross DA, Yamaoka L, Bartlett RJ.; 1986 Jul 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=311567

•

Structural analysis of slipped-strand DNA (S-DNA) formed in (CTG)n. (CAG)n repeats from the myotonic dystrophy locus. by Pearson CE, Wang YH, Griffith JD, Sinden RR.; 1998 Feb 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=147324

•

Transcriptional abnormality in myotonic dystrophy affects DMPK but not neighboring genes. by Hamshere MG, Newman EE, Alwazzan M, Athwal BS, Brook JD.; 1997 Jul 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23832

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Triple Repeat Expansion in Myotonic Dystrophy Alters the Adjacent Chromatin Structure. by Otten AD, Tapscott SJ.; 1995 Jun 6; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=41715

•

Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein. by Michalowski S, Miller JW, Urbinati CR, Paliouras M, Swanson MS, Griffith J.; 1999 Sep 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=148598

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web 6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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Myotonic Dystrophy

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 myotonic dystrophy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “myotonic dystrophy” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for myotonic dystrophy (hyperlinks lead to article summaries): •

A case of congenital myotonic dystrophy presented with diaphragmatic paresis during the neonatal period. Author(s): Yong SC, Boo NY, Ong LC. Source: Journal of Paediatrics and Child Health. 2003 September-October; 39(7): 567-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12969218

•

A combined technique utilising regional anaesthesia and target-controlled sedation in a patient with myotonic dystrophy. Author(s): Aquilina A, Groves J. Source: Anaesthesia. 2002 April; 57(4): 385-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939999

•

A mammalian radial spokehead-like gene, RSHL1, at the myotonic dystrophy-1 locus. Author(s): Eriksson M, Ansved T, Anvret M, Carey N. Source: Biochemical and Biophysical Research Communications. 2001 March 9; 281(4): 835-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11237735

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A patient with myotonic dystrophy type 1 (DM 1) accompanied by laryngeal and renal cell carcinomas had a small CTG triplet repeat expansion but no somatic instability in normal tissues. Author(s): Kinoshita M, Osanai R, Kikkawa M, Adachi A, Ohtake T, Komori T, Hashimoto K, Itoyama S, Mitarai T, Hirose K. Source: Intern Med. 2002 April; 41(4): 312-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11993794

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A safe anesthetic method using caudal block and ketamine for the child with congenital myotonic dystrophy. Author(s): Shiraishi M, Minami K, Kadaya T. Source: Anesthesia and Analgesia. 2002 January; 94(1): 233. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11772836

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A successful strategy for preimplantation genetic diagnosis of myotonic dystrophy using multiplex fluorescent PCR. Author(s): Piyamongkol W, Harper JC, Sherlock JK, Doshi A, Serhal PF, Delhanty JD, Wells D. Source: Prenatal Diagnosis. 2001 March; 21(3): 223-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11260612

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A tRNA(Ala) mutation causing mitochondrial myopathy clinically resembling myotonic dystrophy. Author(s): Horvath R, Lochmuller H, Scharfe C, Do BH, Oefner PJ, Muller-Hocker J, Schoser BG, Pongratz D, Auer DP, Jaksch M. Source: Journal of Medical Genetics. 2003 October; 40(10): 752-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14569122

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Aberrant regulation of insulin receptor alternative splicing is associated with insulin resistance in myotonic dystrophy. Author(s): Savkur RS, Philips AV, Cooper TA. Source: Nature Genetics. 2001 September; 29(1): 40-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11528389

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Abnormal release of incretins and cortisol after oral glucose in subjects with insulinresistant myotonic dystrophy. Author(s): Johansson A, Olsson T, Cederquist K, Forsberg H, Holst JJ, Seckl JR, Ahren B. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 2002 March; 146(3): 397-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11888847

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Altered expression of CUG binding protein 1 mRNA in myotonic dystrophy 1: possible RNA-RNA interaction. Author(s): Watanabe T, Takagi A, Sasagawa N, Ishiura S, Nakase H. Source: Neuroscience Research. 2004 May; 49(1): 47-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15099703

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An expanded CTG trinucleotide repeat causes trans RNA interference: a new hypothesis for the pathogenesis of myotonic dystrophy. Author(s): Sasagawa N, Takahashi N, Suzuki K, Ishiura S. Source: Biochemical and Biophysical Research Communications. 1999 October 14; 264(1): 76-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10527844

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Anaesthesia and myotonic dystrophy. Author(s): Coakley JH, Calverley PM. Source: Lancet. 1990 February 17; 335(8686): 409. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1968131

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Anaesthetic management of a patient with myotonic dystrophy. Author(s): White RJ, Bass S. Source: Paediatric Anaesthesia. 2001 July; 11(4): 494-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11442872

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Ascertainment of myotonic dystrophy through cataract by selective screening. Author(s): Kidd A, Turnpenny P, Kelly K, Clark C, Church W, Hutchinson C, Dean JC, Haites NE. Source: Journal of Medical Genetics. 1995 July; 32(7): 519-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7562963

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Assessment of autonomic nerve function in myotonic dystrophy. Author(s): Olofsson BO, Niklasson U, Forsberg H, Bjerle P, Andersson S, Henriksson A. Source: Journal of the Autonomic Nervous System. 1990 March; 29(3): 187-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2341696

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Assessment of cardiovascular autonomic function in myotonic dystrophy type 2 (DM2/PROMM). Author(s): Flachenecker P, Schneider C, Cursiefen S, Ricker K, Toyka KV, Reiners K. Source: Neuromuscular Disorders : Nmd. 2003 May; 13(4): 289-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12868497

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Assignment of seven genes to distinct intervals on the midportion of human chromosome 19q surrounding the myotonic dystrophy gene region. Author(s): Schonk D, van Dijk P, Riegmann P, Trapman J, Holm C, Willcocks TC, Sillekens P, van Venrooij W, Wimmer E, Geurts van Kessel A, et al. Source: Cytogenetics and Cell Genetics. 1990; 54(1-2): 15-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1701111

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Association of spinal and bulbar muscular atrophy with myotonic dystrophy type 1. Author(s): Jinnai K, Nishimoto K, Itoh K, Hashimoto K, Takahashi K. Source: Muscle & Nerve. 2004 May; 29(5): 729-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15116379

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Baclofen trial in six myotonic dystrophy patients. Author(s): Guilleminault C, Flagg WH, Coburn SC, Dement WC. Source: Acta Neurologica Scandinavica. 1978 March; 57(3): 232-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=352086

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Balanced reciprocal translocation between two D-group chromosomes in a family with myotonic dystrophy. Author(s): Bowen P, Lee CS, Harvey JC. Source: The American Journal of the Medical Sciences. 1968 June; 255: 368-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5654955

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Basal metabolic rate in myotonic dystrophy: evidence against hypometabolism. Author(s): Jozefowicz RF, Welle SL, Nair KS, Kingston WJ, Griggs RC. Source: Neurology. 1987 June; 37(6): 1021-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3587621

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Basal metabolic rate in patients with hydrocephalus. On the cause of lowered basal metabolic rate in myotonic dystrophy. Author(s): Hidle I, Sjaastad O. Source: Acta Neurologica Scandinavica. 1976 March; 53(3): 237-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1266570

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Beta-adrenergic system in myotonic dystrophy. Author(s): Somer H, Maki T, Harkonen M. Source: Journal of the Neurological Sciences. 1992 September; 111(2): 214-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1331339

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Bilateral optic nerve atrophy in myotonic dystrophy. Author(s): Gamez J, Montane D, Martorell L, Minoves T, Cervera C. Source: American Journal of Ophthalmology. 2001 March; 131(3): 398-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11239886

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Binding activity and autophosphorylation of the insulin receptor from patients with myotonic dystrophy. Author(s): Kakehi T, Kuzuya H, Kosaki A, Yamada K, Yoshimasa Y, Okamoto M, Nishimura H, Nishitani H, Saida K, Kuno S, et al. Source: The Journal of Laboratory and Clinical Medicine. 1990 June; 115(6): 688-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2195130

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Biochemical study in myotonic dystrophy. Author(s): Pendefunda G, Ciobanu M, Stefanache F. Source: Rev Med Chir Soc Med Nat Iasi. 1975 July-September; 79(3): 361-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1188215

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Biomedicine. Reconstructing myotonic dystrophy. Author(s): Tapscott SJ, Thornton CA. Source: Science. 2001 August 3; 293(5531): 816-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486078

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Biphasic response on oral glucose tolerance testing in myotonic dystrophy. Author(s): Russell D, Sjaastad O. Source: Acta Neurologica Scandinavica. 1976 March; 53(3): 226-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1266569

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Blood pressure and myotonic dystrophy. Author(s): O'Brien T, Harper PS, Newcombe RG. Source: Clinical Genetics. 1983 June; 23(6): 422-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6883787

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Blunted coronary reserve in myotonic dystrophy. An early and gene-related phenomenon. Author(s): Annane D, Merlet P, Radvanyi H, Mazoyer B, Eymard B, Fiorelli M, Junien C, Fardeau M, Ounnoughene Z, Gajdos P, Syrota A, Duboc D. Source: Circulation. 1996 September 1; 94(5): 973-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8790034

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Bone anomalies in myotonic dystrophy. Author(s): Rodriguez JR, Castillo J, Leira R, Pardo J, Lema M, Noya M. Source: Acta Neurologica Scandinavica. 1991 June; 83(6): 360-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1887757

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Brain disease and molecular analysis in myotonic dystrophy. Author(s): Damian MS, Bachmann G, Koch MC, Schilling G, Stoppler S, Dorndorf W. Source: Neuroreport. 1994 December 20; 5(18): 2549-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7696601

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Brain involvement in myotonic dystrophy: MRI features and their relationship to clinical and cognitive conditions. Author(s): Censori B, Provinciali L, Danni M, Chiaramoni L, Maricotti M, Foschi N, Del Pesce M, Salvolini U. Source: Acta Neurologica Scandinavica. 1994 September; 90(3): 211-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7847063

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Brain MRI features of congenital- and adult-form myotonic dystrophy type 1: casecontrol study. Author(s): Di Costanzo A, Di Salle F, Santoro L, Bonavita V, Tedeschi G. Source: Neuromuscular Disorders : Nmd. 2002 June; 12(5): 476-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12031621

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Brain proton magnetic resonance spectroscopy and brain atrophy in myotonic dystrophy. Author(s): Akiguchi I, Nakano S, Shiino A, Kimura R, Inubushi T, Handa J, Nakamura M, Tanaka M, Oka N, Kimura J. Source: Archives of Neurology. 1999 March; 56(3): 325-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10190823

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Breathing during sleep in patients with myotonic dystrophy and non-myotonic respiratory muscle weakness. Author(s): Gilmartin JJ, Cooper BG, Griffiths CJ, Walls TJ, Veale D, Stone TN, Osselton JW, Hudgson P, Gibson GJ. Source: The Quarterly Journal of Medicine. 1991 January; 78(285): 21-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1670061

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Breathing pattern awake and asleep in myotonic dystrophy. Author(s): Ververs CC, Van der Meche FG, Verbraak AF, van der Sluys HC, Bogaard JM. Source: Respiration; International Review of Thoracic Diseases. 1996; 63(1): 1-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8833986

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Breathing pattern awake and asleep in patients with myotonic dystrophy. Author(s): Veale D, Cooper BG, Gilmartin JJ, Walls TJ, Griffith CJ, Gibson GJ. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1995 May; 8(5): 815-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7656955

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Cardiac involvement and CTG expansion in myotonic dystrophy. Author(s): Merlevede K, Vermander D, Theys P, Legius E, Ector H, Robberecht W. Source: Journal of Neurology. 2002 June; 249(6): 693-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12111301

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Cardiac involvement in patients with myotonic dystrophy: characteristic features of magnetic resonance imaging. Author(s): De Ambroggi L, Raisaro A, Marchiano V, Radice S, Meola G. Source: European Heart Journal. 1995 July; 16(7): 1007-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7498193

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Cardiovascular autonomic control in myotonic dystrophy type 1: a correlative study with clinical and genetic data. Author(s): Di Leo R, Rodolico C, De Gregorio C, Recupero A, Coglitore S, Annesi G, Toscano A, Messina C, Vita G. Source: Neuromuscular Disorders : Nmd. 2004 February; 14(2): 136-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14733960

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Cdc42 antagonizes inductive action of cAMP on cell shape, via effects of the myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) on myosin light chain phosphorylation. Author(s): Dong JM, Leung T, Manser E, Lim L. Source: European Journal of Cell Biology. 2002 April; 81(4): 231-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12018391

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Changes in myotonic dystrophy protein kinase levels and muscle development in congenital myotonic dystrophy. Author(s): Furling D, Lam le T, Agbulut O, Butler-Browne GS, Morris GE. Source: American Journal of Pathology. 2003 March; 162(3): 1001-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12598332

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Characterization of myotonic dystrophy kinase (DMK) protein in human and rodent muscle and central nervous tissue. Author(s): Whiting EJ, Waring JD, Tamai K, Somerville MJ, Hincke M, Staines WA, Ikeda JE, Korneluk RG. Source: Human Molecular Genetics. 1995 June; 4(6): 1063-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7655460

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Cis and trans effects of the myotonic dystrophy (DM) mutation in a cell culture model. Author(s): Amack JD, Paguio AP, Mahadevan MS. Source: Human Molecular Genetics. 1999 October; 8(11): 1975-84. Erratum In: Hum Mol Genet 1999 December; 8(13): 2573. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10484765

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Cognitive function in early adult and adult onset myotonic dystrophy. Author(s): Van Spaendonck KP, Ter Bruggen JP, Weyn Banningh EW, Maassen BA, Van de Biezenbos JB, Gabreels FJ. Source: Acta Neurologica Scandinavica. 1995 June; 91(6): 456-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7572040

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Confirmation of the type 2 myotonic dystrophy (CCTG)n expansion mutation in patients with proximal myotonic myopathy/proximal myotonic dystrophy of different European origins: a single shared haplotype indicates an ancestral founder effect. Author(s): Bachinski LL, Udd B, Meola G, Sansone V, Bassez G, Eymard B, Thornton CA, Moxley RT, Harper PS, Rogers MT, Jurkat-Rott K, Lehmann-Horn F, Wieser T, Gamez J, Navarro C, Bottani A, Kohler A, Shriver MD, Sallinen R, Wessman M, Zhang S, Wright FA, Krahe R. Source: American Journal of Human Genetics. 2003 October; 73(4): 835-48. Epub 2003 September 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12970845

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Congenital myotonic dystrophy: assisted ventilation duration and outcome. Author(s): Campbell C, Sherlock R, Jacob P, Blayney M. Source: Pediatrics. 2004 April; 113(4): 811-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15060232

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Congenital myotonic dystrophy: molecular diagnosis and clinical study. Author(s): Hojo K, Yamagata H, Moji H, Fujita T, Miki T, Fujimura M, Kidoguchi K. Source: American Journal of Perinatology. 1995 May; 12(3): 195-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7612095

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Congenital myotonic dystrophy: report of one case. Author(s): Liao YH, Sue WC, Jang DR, Soong BW, Peng S, Chou GS. Source: Acta Paediatr Taiwan. 2003 May-June; 44(3): 155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521021

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Contribution of abnormal insulin secretion and insulin resistance to the pathogenesis of type 2 diabetes in myotonic dystrophy. Author(s): Perseghin G, Caumo A, Arcelloni C, Benedini S, Lanzi R, Pagliato E, Sereni LP, Testolin G, Battezzati A, Comi G, Comola M, Luzi L. Source: Diabetes Care. 2003 July; 26(7): 2112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832322

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Correlation between cardiac involvement and CTG repeat amplification in myotonic dystrophy type 1. Author(s): Rakocevic-Stojanovic V, Savic D, Pavlovic S, Lavrnic D, Romac S, Apostolski S. Source: Acta Myol. 2003 May; 22(1): 26-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12966702

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Creatine monohydrate in myotonic dystrophy: a double-blind, placebo-controlled clinical study. Author(s): Walter MC, Reilich P, Lochmuller H, Kohnen R, Schlotter B, Hautmann H, Dunkl E, Pongratz D, Muller-Felber W. Source: Journal of Neurology. 2002 December; 249(12): 1717-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12529796

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CTG instability in myotonic dystrophy: molecular genetic analysis of families from south-eastern France with characteristics of intergenerational variation in CGT repeat numbers. Author(s): Duthel S, Bost M, Ollagnon E, Vial C, Petiot P, Chazot G, Vandenberghe A. Source: Annales De Genetique. 1999; 42(3): 151-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10526658

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CTG repeat number at the myotonic dystrophy locus in healthy Kuwaiti individuals: possible explanation of why myotonic dystrophy is rare in Kuwait. Author(s): Alfadhli S, Elshafey AE, Bastaki L, Al-Awadi S. Source: Archives of Neurology. 2004 June; 61(6): 895-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15210527

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CTG repeats distribution and Alu insertion polymorphism at myotonic dystrophy (DM) gene in Amhara and Oromo populations of Ethiopia. Author(s): Gennarelli M, Pavoni M, Cruciani F, De Stefano G, Dallapiccola B, Novelli G. Source: Human Genetics. 1999 July-August; 105(1-2): 165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480373

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Cystic insulinoma of the pancreas in a patient with myotonic dystrophy: correlation of imaging and pathologic findings. Author(s): Vandecaveye V, Verswijvel G, Colla P, Verhelst H, VanRobaeys J, Palmers Y. Source: Jbr-Btr. 2003 September-October; 86(5): 268-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14651081

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Deconstructing myotonic dystrophy. Author(s): Tapscott SJ. Source: Science. 2000 September 8; 289(5485): 1701-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11001736

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Decrease of neurons in the medullary arcuate nucleus in myotonic dystrophy. Author(s): Ono S, Takahashi K, Kanda F, Jinnai K, Fukuoka Y, Mitake S, Inagaki T, Kurisaki H, Nagao K, Shimizu N. Source: Acta Neuropathologica. 2001 July; 102(1): 89-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11547956

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Decreased DMPK transcript levels in myotonic dystrophy 1 type IIA muscle fibers. Author(s): Eriksson M, Hedberg B, Carey N, Ansved T. Source: Biochemical and Biophysical Research Communications. 2001 September 7; 286(5): 1177-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11527424

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Decreased hypocretin-1 (Orexin-A) levels in the cerebrospinal fluid of patients with myotonic dystrophy and excessive daytime sleepiness. Author(s): Martinez-Rodriguez JE, Lin L, Iranzo A, Genis D, Marti MJ, Santamaria J, Mignot E. Source: Sleep. 2003 May 1; 26(3): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12749547

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Decreased levels of myotonic dystrophy protein kinase (DMPK) and delayed differentiation in human myotonic dystrophy myoblasts. Author(s): Furling D, Lemieux D, Taneja K, Puymirat J. Source: Neuromuscular Disorders : Nmd. 2001 November; 11(8): 728-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11595515

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Defective satellite cells in congenital myotonic dystrophy. Author(s): Furling D, Coiffier L, Mouly V, Barbet JP, St Guily JL, Taneja K, Gourdon G, Junien C, Butler-Browne GS. Source: Human Molecular Genetics. 2001 September 15; 10(19): 2079-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590125

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Delineation of CTG repeats and clinical features in a Taiwanese myotonic dystrophy family. Author(s): Jou SB, Lin HM, Pan H, Chiu YL, Li SY, Lee CC, Hsiao KM. Source: Proc Natl Sci Counc Repub China B. 2001 January; 25(1): 40-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11254171

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Detection of DNA fragmentation of myonuclei in myotonic dystrophy by double staining with anti-emerin antibody and by nick end-labeling. Author(s): Yamada H, Nakagawa M, Higuchi I, Horikiri T, Osame M. Source: Journal of the Neurological Sciences. 2000 February 15; 173(2): 97-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10675651

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Developmental expression of myotonic dystrophy protein kinase in brain and its relevance to clinical phenotype. Author(s): Endo A, Motonaga K, Arahata K, Harada K, Yamada T, Takashima S. Source: Acta Neuropathologica. 2000 November; 100(5): 513-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11045673

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Dilated Virchow-Robin spaces in myotonic dystrophy: frequency, extent and significance. Author(s): Di Costanzo A, Di Salle F, Santoro L, Bonavita V, Tedeschi G. Source: European Neurology. 2001; 46(3): 131-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11598331

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Disorders of eye movement in myotonic dystrophy. Author(s): Ter Bruggen JP, Bastiaensen LA, Tyssen CC, Gielen G. Source: Brain; a Journal of Neurology. 1990 April; 113 ( Pt 2): 463-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2328413

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DNA analysis in a suspected individual with myotonic dystrophy family history and her abortus. Author(s): Bi X, Xie H, Zheng H, Ding S, Zhang S, Wang Y, Xu Z, Ren D. Source: Chinese Medical Journal. 2002 November; 115(11): 1628-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12609075

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Does (CUG)n repeat in DMPK mRNA 'paint' chromosome 19 to suppress distant genes to create the diverse phenotype of myotonic dystrophy?: A new hypothesis of long-range cis autosomal inactivation. Author(s): Junghans RP, Ebralidze A, Tiwari B. Source: Neurogenetics. 2001 March; 3(2): 59-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11354827

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Does abnormal neuronal excitability exist in myotonic dystrophy? I. Effects of the antiarrhythmic drug hydroquinidine on slow saccadic eye movements. Author(s): Di Costanzo A, Mottola A, Toriello A, Di Iorio G, Tedeschi G, Bonavita V. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2000 April; 21(2): 73-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10938184

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Does abnormal neuronal excitability exist in myotonic dystrophy? II. Effects of the antiarrhythmic drug hydroquinidine on apathy and hypersomnia. Author(s): Di Costanzo A, Mottola A, Toriello A, Di Iorio G, Tedeschi G, Bonavita V. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2000 April; 21(2): 81-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10938185

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Does cytosine-thymine-guanine (CTG) expansion size predict cardiac events and electrocardiographic progression in myotonic dystrophy? Author(s): Clarke NR, Kelion AD, Nixon J, Hilton-Jones D, Forfar JC. Source: Heart (British Cardiac Society). 2001 October; 86(4): 411-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11559681

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Domiciliary-assisted ventilation in patients with myotonic dystrophy. Author(s): Nugent AM, Smith IE, Shneerson JM. Source: Chest. 2002 February; 121(2): 459-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11834657

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Drosophila homolog of the myotonic dystrophy-associated gene, SIX5, is required for muscle and gonad development. Author(s): Kirby RJ, Hamilton GM, Finnegan DJ, Johnson KJ, Jarman AP. Source: Current Biology : Cb. 2001 July 10; 11(13): 1044-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11470409

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Dysregulation of human brain microtubule-associated tau mRNA maturation in myotonic dystrophy type 1. Author(s): Sergeant N, Sablonniere B, Schraen-Maschke S, Ghestem A, Maurage CA, Wattez A, Vermersch P, Delacourte A. Source: Human Molecular Genetics. 2001 September 15; 10(19): 2143-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11590131

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Early development of megarectum in myotonic dystrophy. Author(s): Meijers B, Miserez M, Veerman-Wouters G, Fryns JP. Source: Clinical Genetics. 2002 May; 61(5): 391-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12081728

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Effect of triplet repeat expansion on chromatin structure and expression of DMPK and neighboring genes, SIX5 and DMWD, in myotonic dystrophy. Author(s): Frisch R, Singleton KR, Moses PA, Gonzalez IL, Carango P, Marks HG, Funanage VL. Source: Molecular Genetics and Metabolism. 2001 September-October; 74(1-2): 281-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11592825

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Effects of high resistance training in patients with myotonic dystrophy. Author(s): Tollback A, Eriksson S, Wredenberg A, Jenner G, Vargas R, Borg K, Ansved T. Source: Scandinavian Journal of Rehabilitation Medicine. 1999 March; 31(1): 9-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10229998

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Eight years' experience of direct molecular testing for myotonic dystrophy in Wales. Author(s): Fokstuen S, Myring J, Meredith L, Ravine D, Harper PS. Source: Journal of Medical Genetics. 2001 December; 38(12): E42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11748308

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Electrophysiological evaluation in myotonic dystrophy: correlation with CTG length expansion. Author(s): Pfeilsticker BH, Bertuzzo CS, Nucci A. Source: Arquivos De Neuro-Psiquiatria. 2001 June; 59(2-A): 186-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11400022

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Electrophysiological evaluation of oropharyngeal swallowing in myotonic dystrophy. Author(s): Ertekin C, Yuceyar N, Aydogdu, Karasoy H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2001 March; 70(3): 363-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11181860

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Elongation of (CTG)n repeats in myotonic dystrophy protein kinase gene in tumors associated with myotonic dystrophy patients. Author(s): Jinnai K, Sugio T, Mitani M, Hashimoto K, Takahashi K. Source: Muscle & Nerve. 1999 September; 22(9): 1271-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10454725

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Emotional and behavioral profile and child psychiatric diagnosis in the childhood type of myotonic dystrophy. Author(s): Goossens E, Steyaert J, De Die-Smulders C, Willekens D, Fryns JP. Source: Genet Couns. 2000; 11(4): 317-27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11140408

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Epidemiological and genetic studies of myotonic dystrophy type 1 in Taiwan. Author(s): Hsiao KM, Chen SS, Li SY, Chiang SY, Lin HM, Pan H, Huang CC, Kuo HC, Jou SB, Su CC, Ro LS, Liu CS, Lo MC, Chen CM, Lin CC. Source: Neuroepidemiology. 2003 September-October; 22(5): 283-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902623

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Epidemiology of myotonic dystrophy in Italy: re-apprisal after genetic diagnosis. Author(s): Siciliano G, Manca M, Gennarelli M, Angelini C, Rocchi A, Iudice A, Miorin M, Mostacciuolo M. Source: Clinical Genetics. 2001 May; 59(5): 344-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11359466

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ETR-1, a homologue of a protein linked to myotonic dystrophy, is essential for muscle development in Caenorhabditis elegans. Author(s): Milne CA, Hodgkin J. Source: Current Biology : Cb. 1999 November 4; 9(21): 1243-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10556089

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Exaggerated physiological responses to propofol in myotonic dystrophy. Author(s): Speedy H. Source: British Journal of Anaesthesia. 1990 January; 64(1): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2302369

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Excessive daytime sleepiness in myotonic dystrophy. Author(s): Giubilei F, Antonini G, Bastianello S, Morino S, Paolillo A, Fiorelli M, Ferretti C, Fieschi C. Source: Journal of the Neurological Sciences. 1999 March 15; 164(1): 60-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10385049

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Excessive daytime somnolence and increased rapid eye movement pressure in myotonic dystrophy. Author(s): Gibbs JW 3rd, Ciafaloni E, Radtke RA. Source: Sleep. 2002 September 15; 25(6): 672-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12224846

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Excessive daytime somnolence and increased rapid eye movement pressure in myotonic dystrophy. Author(s): Thorpy M. Source: Curr Neurol Neurosci Rep. 2003 March; 3(2): 165-6. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12583846

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Executive dysfunction and avoidant personality trait in myotonic dystrophy type 1 (DM-1) and in proximal myotonic myopathy (PROMM/DM-2). Author(s): Meola G, Sansone V, Perani D, Scarone S, Cappa S, Dragoni C, Cattaneo E, Cotelli M, Gobbo C, Fazio F, Siciliano G, Mancuso M, Vitelli E, Zhang S, Krahe R, Moxley RT. Source: Neuromuscular Disorders : Nmd. 2003 December; 13(10): 813-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678804

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Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel premRNA and hyperexcitability of skeletal muscle in myotonic dystrophy. Author(s): Mankodi A, Takahashi MP, Jiang H, Beck CL, Bowers WJ, Moxley RT, Cannon SC, Thornton CA. Source: Molecular Cell. 2002 July; 10(1): 35-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12150905

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Expanding complexity in myotonic dystrophy. Author(s): Groenen P, Wieringa B. Source: Bioessays : News and Reviews in Molecular, Cellular and Developmental Biology. 1998 November; 20(11): 901-12. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9872056

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Expansion of CTG repeat in myotonin protein kinase gene on Alu(ins)-HinfI-I background in a myotonic dystrophy patient from India. Mutations in brief no. 210. Online. Author(s): Basu P, Gangopadhaya PK, Murkherjee SC, Sinha KK, Bhattacharyya NP. Source: Human Mutation. 1999; 13(1): 84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10189221

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Expression of the myotonic dystrophy locus-associated homeodomain protein in congenital myotonic dystrophy. Author(s): Tachi N, Ohya K, Chiba S. Source: Journal of Child Neurology. 1999 July; 14(7): 471-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10573472

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Faecal incontinence in myotonic dystrophy. Author(s): Abercrombie JF, Rogers J, Swash M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1998 January; 64(1): 12830. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9436743

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Familial left ventricular hypertrabeculation in myotonic dystrophy type 1. Author(s): Finsterer J, Stollberger C, Kopsa W. Source: Herz. 2003 August; 28(5): 466-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12928748

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Fertility in myotonic dystrophy in Saguenay-Lac-St-Jean: a historical perspective. Author(s): Dao TN, Mathieu J, Bouchard JP, De Braekeleer M. Source: Clinical Genetics. 1992 November; 42(5): 234-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1486700

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Fetal akinesia-hypokinesia deformation sequence (FADS) in 2 siblings with congenital myotonic dystrophy. Author(s): Lidang Jensen M, Rix M, Schroder HD, Teglbjaerg PS, Ebbesen F. Source: Clin Neuropathol. 1995 March-April; 14(2): 105-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7606895

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Fission yeast orb6, a ser/thr protein kinase related to mammalian rho kinase and myotonic dystrophy kinase, is required for maintenance of cell polarity and coordinates cell morphogenesis with the cell cycle. Author(s): Verde F, Wiley DJ, Nurse P. Source: Proceedings of the National Academy of Sciences of the United States of America. 1998 June 23; 95(13): 7526-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636183

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Fluorescence in situ hybridization analysis of the replication properties of the myotonic dystrophy protein kinase (DMPK) gene region. Author(s): Rajcan-Separovic E, Barcelo JM, Korneluk RG. Source: Cytogenetics and Cell Genetics. 1998; 82(3-4): 247-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9858828

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Fluorescent PCR and automated fragment analysis for the clinical application of preimplantation genetic diagnosis of myotonic dystrophy (Steinert's disease). Author(s): Sermon K, De Vos A, Van de Velde H, Seneca S, Lissens W, Joris H, Vandervorst M, Van Steirteghem A, Liebaers I. Source: Molecular Human Reproduction. 1998 August; 4(8): 791-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9733437

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Foci of trinucleotide repeat transcripts in nuclei of myotonic dystrophy cells and tissues. Author(s): Taneja KL, McCurrach M, Schalling M, Housman D, Singer RH. Source: The Journal of Cell Biology. 1995 March; 128(6): 995-1002. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7896884

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Follicular cyst in a patient with myotonic dystrophy: a case of cyst with differentiation toward follicular infundibulum, isthmus, inner root sheath, and hair. Author(s): Nishie W, Iitoyo M, Miyazawa H. Source: The American Journal of Dermatopathology. 2001 December; 23(6): 521-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11801793

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Forearm 3-methylhistidine efflux in myotonic dystrophy. Author(s): Rifai Z, Kingston WJ, McCraith B, Moxley RT 3rd. Source: Annals of Neurology. 1993 November; 34(5): 682-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8239562

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Founder effect and prevalence of myotonic dystrophy in South Africans: molecular studies. Author(s): Goldman A, Krause A, Ramsay M, Jenkins T. Source: American Journal of Human Genetics. 1996 August; 59(2): 445-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8755933

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Foveal photopigment kinetics--abnormality: an early sign in myotonic dystrophy? Author(s): ter Bruggen JP, van Meel GJ, Paridaens AD, Tijssen CC, van Norren D. Source: The British Journal of Ophthalmology. 1992 October; 76(10): 594-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1420041

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Fragile-X syndrome and myotonic dystrophy: parallels and paradoxes. Author(s): Tapscott SJ, Klesert TR, Widrow RJ, Stoger R, Laird CD. Source: Current Opinion in Genetics & Development. 1998 April; 8(2): 245-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9610417

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Free radicals, lipid peroxides and antioxidants in blood of patients with myotonic dystrophy. Author(s): Ihara Y, Mori A, Hayabara T, Namba R, Nobukuni K, Sato K, Miyata S, Edamatsu R, Liu J, Kawai M. Source: Journal of Neurology. 1995 February; 242(3): 119-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7751852

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French myotonic dystrophy families show expansion of a CTG repeat in complete linkage disequilibrium with an intragenic 1 kb insertion. Author(s): Lavedan C, Hofmann-Radvanyi H, Boileau C, Bonaiti-Pellie C, Savoy D, Shelbourne P, Duros C, Rabes JP, Dehaupas I, Luce S, et al. Source: Journal of Medical Genetics. 1994 January; 31(1): 33-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8151634

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Frequency and stability of the myotonic dystrophy type 1 premutation. Author(s): Martorell L, Monckton DG, Sanchez A, Lopez De Munain A, Baiget M. Source: Neurology. 2001 February 13; 56(3): 328-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11171897

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Frequency of intergenerational contractions of the CTG repeats in myotonic dystrophy. Author(s): Lopez de Munain A, Cobo AM, Saenz A, Blanco A, Poza JJ, Martorell L, Marti-Masso JF, Baiget M. Source: Genetic Epidemiology. 1996; 13(5): 483-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8905394

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Frequency of myotonic dystrophy gene carriers in cataract patients. Author(s): Cobo AM, Poza JJ, Blanco A, Lopez de Munain A, Saenz A, Azpitarte M, Marchessi J, Marti Masso JF. Source: Journal of Medical Genetics. 1996 March; 33(3): 221-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8728695

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Functional deterioration and selenium-vitamin E treatment in myotonic dystrophy. A placebo-controlled study. Author(s): Orndahl G, Grimby G, Grimby A, Johansson G, Wilhelmsen L. Source: Journal of Internal Medicine. 1994 March; 235(3): 205-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8120515

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Further evidence for a major ancient mutation underlying myotonic dystrophy from linkage disequilibrium studies in the Japanese population. Author(s): Yamagata H, Nakagawa M, Johnson K, Miki T. Source: Journal of Human Genetics. 1998; 43(4): 246-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9852676

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Gastric emptying in myotonic dystrophy. Author(s): Ronnblom A, Andersson S, Hellstrom PM, Danielsson A. Source: European Journal of Clinical Investigation. 2002 August; 32(8): 570-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12190956

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Gastric myoelectrical activity and gut hormone secretion in myotonic dystrophy. Author(s): Ronnblom A, Hellstrom PM, Holst JJ, Theodorsson E, Danielsson A. Source: European Journal of Gastroenterology & Hepatology. 2001 July; 13(7): 825-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11474313

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Gastric volvulus complicating myotonic dystrophy. Author(s): Kusunoki M, Hatada T, Ikeuchi H, Okamoto T, Sakanoue Y, Utsunomiya J. Source: Hepatogastroenterology. 1992 December; 39(6): 586-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1483675

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Gastrointestinal symptoms in myotonic dystrophy. Author(s): Ronnblom A, Forsberg H, Danielsson A. Source: Scandinavian Journal of Gastroenterology. 1996 July; 31(7): 654-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8819213

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Genealogical reconstruction of myotonic dystrophy in the Saguenay-Lac-Saint-Jean area (Quebec, Canada). Author(s): Mathieu J, De Braekeleer M, Prevost C. Source: Neurology. 1990 May; 40(5): 839-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2330114

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Genetic counselling for myotonic dystrophy: a comparison of lens examination and DNA linkage studies. Author(s): Longstaff S, Curtis D, Quick J, Talbot J. Source: Eye (London, England). 1991; 5 ( Pt 1): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1676377

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Genetic epidemiology of myotonic dystrophy in Istria, Croatia. Author(s): Medica I, Markovic D, Peterlin B. Source: Acta Neurologica Scandinavica. 1997 March; 95(3): 164-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9088385

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Genetic linkage with chromosome 19 but not chromosome 17 in a family with myotonic dystrophy associated with hereditary motor and sensory neuropathy. Author(s): Brunner HG, Spaans F, Smeets HJ, Coerwinkel-Driessen M, Hulsebos T, Wieringa B, Ropers HH. Source: Neurology. 1991 January; 41(1): 80-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1985299

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Genetic mapping of a second myotonic dystrophy locus. Author(s): Ranum LP, Rasmussen PF, Benzow KA, Koob MD, Day JW. Source: Nature Genetics. 1998 June; 19(2): 196-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9620781

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Genetic risks for children of women with myotonic dystrophy. Author(s): Goodship J, Gibson DE, Burn J, Honeyman J, Cubey RB, Schofield I. Source: American Journal of Human Genetics. 1992 June; 50(6): 1340-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1530708

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Genetic risks for children of women with myotonic dystrophy. Author(s): Koch MC, Grimm T, Harley HG, Harper PS. Source: American Journal of Human Genetics. 1991 June; 48(6): 1084-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2035529

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Genomic instability associated with myotonic dystrophy does not involve p53 expression and activity. Author(s): Gennarelli M, Lucarelli M, Amicucci P, Soddu S, Novelli G, Dallapiccola B. Source: Cell Biochemistry and Function. 1998 June; 16(2): 117-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9636999

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Genomic organization and transcriptional units at the myotonic dystrophy locus. Author(s): Shaw DJ, McCurrach M, Rundle SA, Harley HG, Crow SR, Sohn R, Thirion JP, Hamshere MG, Buckler AJ, Harper PS, et al. Source: Genomics. 1993 December; 18(3): 673-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7905855

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Genomic organization of human myotonic dystrophy kinase-related Cdc42-binding kinase alpha reveals multiple alternative splicing and functional diversity. Author(s): Tan I, Cheong A, Lim L, Leung T. Source: Gene. 2003 January 30; 304: 107-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12568720

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Genotype-phenotype correlation in myotonic dystrophy. Author(s): Gharehbaghi-Schnell EB, Finsterer J, Korschineck I, Mamoli B, Binder BR. Source: Clinical Genetics. 1998 January; 53(1): 20-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9550357

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Giant hairpins formed by CUG repeats in myotonic dystrophy messenger RNAs might sterically block RNA export through nuclear pores. Author(s): Koch KS, Leffert HL. Source: Journal of Theoretical Biology. 1998 June 21; 192(4): 505-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9680723

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Giardia lamblia infection in a patient with myotonic dystrophy. Author(s): Mouthon L, Godmer P, Piqueras B, Cohen P, Lortholary O, HofmannRadvanyi H, Guillevin L. Source: Annales De Medecine Interne. 2002 December; 153(8): 540-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12610429

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Glucocorticoid metabolism and adrenocortical reactivity to ACTH in myotonic dystrophy. Author(s): Johansson A, Andrew R, Forsberg H, Cederquist K, Walker BR, Olsson T. Source: The Journal of Clinical Endocrinology and Metabolism. 2001 September; 86(9): 4276-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549662

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Gonadal dysfunction in patients with myotonic dystrophy. Author(s): Marinkovic Z, Prelevic G, Wurzburger M, Nogic S. Source: Exp Clin Endocrinol. 1990 September; 96(1): 37-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2126240

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Gonosomal mosaicism in myotonic dystrophy patients: involvement of mitotic events in (CTG)n repeat variation and selection against extreme expansion in sperm. Author(s): Jansen G, Willems P, Coerwinkel M, Nillesen W, Smeets H, Vits L, Howeler C, Brunner H, Wieringa B. Source: American Journal of Human Genetics. 1994 April; 54(4): 575-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8128954

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Hammerhead ribozyme-mediated destruction of nuclear foci in myotonic dystrophy myoblasts. Author(s): Langlois MA, Lee NS, Rossi JJ, Puymirat J. Source: Molecular Therapy : the Journal of the American Society of Gene Therapy. 2003 May; 7(5 Pt 1): 670-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12718910

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Haplotype analysis of congenital myotonic dystrophy patients from asymptomatic DM father. Author(s): Tachi N, Ohya K, Yamagata H, Miki T, Kikuchi K, Chiba S. Source: Pediatric Neurology. 1997 May; 16(4): 315-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9258965

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Haplotype analysis of genomic polymorphisms in and around the myotonic dystrophy locus in diverse populations of India. Author(s): Basu P, Majumder PP, Roychoudhury S, Bhattacharyya NP. Source: Human Genetics. 2001 April; 108(4): 310-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11379877

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Haplotype analysis of the myotonic dystrophy type 1 (DM1) locus in Taiwan: implications for low prevalence and founder mutations of Taiwanese myotonic dystrophy type 1. Author(s): Pan H, Lin HM, Ku WY, Li TC, Li SY, Lin CC, Hsiao KM. Source: European Journal of Human Genetics : Ejhg. 2001 August; 9(8): 638-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11528511

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Heart rate variability declines with increasing age and CTG repeat length in patients with myotonic dystrophy type 1. Author(s): Hardin BA, Lowe MR, Bhakta D, Groh WJ. Source: Annals of Noninvasive Electrocardiology : the Official Journal of the International Society for Holter and Noninvasive Electrocardiology, Inc. 2003 July; 8(3): 227-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14510658

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Hereditary components in the neurodegerative diseases: Alzheimer's disease and myotonic dystrophy. Author(s): Roses AD. Source: Neurobiology of Aging. 1994 March-April; 15(2): 243-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7838301

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High CTG repeat number in nodular thyroid tissue from a myotonic dystrophy patient. Author(s): Daumerie C, Lannoy N, Squifflet JP, Verellen G, Verellen-Dumoulin C. Source: Journal of Medical Genetics. 1994 November; 31(11): 891-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7853378

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Hirschsprung's disease in myotonic dystrophy. Author(s): Benito-Leon J, Lopez-Fernandez JC, Gutierrez-Rivas E, Ruiz J, Novo O. Source: Muscle & Nerve. 1996 September; 19(9): 1229-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8761284

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Histopathological differences of myotonic dystrophy type 1 (DM1) and PROMM/DM2. Author(s): Vihola A, Bassez G, Meola G, Zhang S, Haapasalo H, Paetau A, Mancinelli E, Rouche A, Hogrel JY, Laforet P, Maisonobe T, Pellissier JF, Krahe R, Eymard B, Udd B. Source: Neurology. 2003 June 10; 60(11): 1854-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12796551

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Homodimerization through coiled-coil regions enhances activity of the myotonic dystrophy protein kinase. Author(s): Zhang R, Epstein HF. Source: Febs Letters. 2003 July 10; 546(2-3): 281-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832055

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Homozygous myotonic dystrophy: clinical and molecular studies of three unrelated cases. Author(s): Martorell L, Illa I, Rosell J, Benitez J, Sedano MJ, Baiget M. Source: Journal of Medical Genetics. 1996 September; 33(9): 783-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8880582

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Hydrocephalus and cognitive decline in myotonic dystrophy: case report and literature review. Author(s): Moroz A, Kalva S. Source: Archives of Physical Medicine and Rehabilitation. 1998 August; 79(8): 1022-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9710180

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Hyperkalaemia and selective hypoaldosteronism in myotonic dystrophy. Author(s): Misra D, DeSilva S, Fellerman H, Dufour DR, Streeten DH, Nylen ES. Source: Clinical Endocrinology. 2002 February; 56(2): 271-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874420

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Hyperkalaemia and selective hypoaldosteronism in myotonic dystrophy. Author(s): Olsson T. Source: Clinical Endocrinology. 2002 February; 56(2): 151-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11874404

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Hypermutable myotonic dystrophy CTG repeats in transgenic mice. Author(s): Monckton DG, Coolbaugh MI, Ashizawa KT, Siciliano MJ, Caskey CT. Source: Nature Genetics. 1997 February; 15(2): 193-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9020848

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Hyperparathyroidism in a patient with myotonic dystrophy. Author(s): Downie A, Jepson EM. Source: Journal of the Royal Society of Medicine. 1990 January; 83(1): 58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2304061

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Hyperproliferation of synapses on spinal motor neurons of Duchenne muscular dystrophy and myotonic dystrophy patients. Author(s): Nagao M, Kato S, Hayashi H, Misawa H. Source: Acta Neuropathologica. 2003 December; 106(6): 557-60. Epub 2003 August 14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12920538

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Hypersomnolence in myotonic dystrophy: demonstration of sleep onset REM sleep. Author(s): Park JD, Radtke RA. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1995 April; 58(4): 512-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7738575

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Hypertrophic cardiomyopathy in congenital myotonic dystrophy. Author(s): Igarashi H, Momoi MY, Yamagata T, Shiraishi H, Eguchi I. Source: Pediatric Neurology. 1998 April; 18(4): 366-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9588538

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Hypo-IgG in myotonic dystrophy is due to a selective reduction of the IgG1-subclass serum level. Author(s): Bruyland M, Lissens W, De Waele M, Demanet C. Source: Muscle & Nerve. 1994 October; 17(10): 1233-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7935539

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Identification of transcriptional targets for Six5: implication for the pathogenesis of myotonic dystrophy type 1. Author(s): Sato S, Nakamura M, Cho DH, Tapscott SJ, Ozaki H, Kawakami K. Source: Human Molecular Genetics. 2002 May 1; 11(9): 1045-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11978764

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Imaging case of the month. Cerebral ventricular dilation and diaphragmatic elevation in congenital myotonic dystrophy. Author(s): Caglar MK, Geven WB. Source: American Journal of Perinatology. 1990 April; 7(2): 198-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2184815

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Immunolocalization of myotonic dystrophy protein kinase in corbular and junctional sarcoplasmic reticulum of human cardiac muscle. Author(s): Ueda H, Kameda N, Baba T, Terada N, Shimokawa M, Yamamoto M, Ishiura S, Kobayashi T, Ohno S. Source: The Histochemical Journal. 1998 April; 30(4): 245-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9610815

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Impaired cerebral glucose metabolism in myotonic dystrophy: a triplet-size dependent phenomenon. Author(s): Annane D, Fiorelli M, Mazoyer B, Pappata S, Eymard B, Radvanyi H, Junien C, Fardeau M, Merlet P, Gajdos P, Syrota A, Sansom Y, Duboc D. Source: Neuromuscular Disorders : Nmd. 1998 February; 8(1): 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565989

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Importance of physical rehabilitation before and after cardiac transplantation in a patient with myotonic dystrophy: a case report. Author(s): Conraads VM, Beckers PJ, Vorlat A, Vrints CJ. Source: Archives of Physical Medicine and Rehabilitation. 2002 May; 83(5): 724-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11994815

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Increased (CTG/CAG)(n) lengths in myotonic dystrophy type 1 and Machado-Joseph disease genes in idiopathic azoospermia patients. Author(s): Pan H, Li YY, Li TC, Tsai WT, Li SY, Hsiao KM. Source: Human Reproduction (Oxford, England). 2002 June; 17(6): 1578-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12042281

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Increased levels of tPA antigen and tPA/PAI-1 complex in myotonic dystrophy. Author(s): Johansson A, Boman K, Cederquist K, Forsberg H, Olsson T. Source: Journal of Internal Medicine. 2001 June; 249(6): 503-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11422656

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Increased plasma concentration of atrial natriuretic hormone in myotonic dystrophy. Author(s): Parlapiano C, Antonini G, Vichi R, Fragola PV, Campana E, Rota C, Borgia MC, Tonnarini G, Negri M. Source: European Neurology. 1998; 39(4): 238-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9635476

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Increased risk for abnormal placentation in women affected by myotonic dystrophy. Author(s): Rudnik-Schoneborn S, Rohrig D, Zerres K. Source: Journal of Perinatal Medicine. 1998; 26(3): 192-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9773377

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Inhibition of naloxone-stimulated adrenocorticotropin release by alprazolam in myotonic dystrophy patients. Author(s): Joyner JM, Grice JE, Hockings GI, Torpy DJ, Crosbie GV, Walters MM, Jackson RV. Source: Journal of Neuroendocrinology. 1998 May; 10(5): 391-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9663654

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Instability in the normal CTG repeat range at the myotonic dystrophy locus. Author(s): Meiner A, Thamm B, Strenge S, Froster U. Source: Journal of Medical Genetics. 1998 September; 35(9): 791. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9733048

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Instability of a premutation allele in homozygous patients with myotonic dystrophy type 1. Author(s): Abbruzzese C, Costanzi Porrini S, Mariani B, Gould FK, McAbney JP, Monckton DG, Ashizawa T, Giacanelli M. Source: Annals of Neurology. 2002 October; 52(4): 435-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12325072

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Instability of the (CTG)n repeat in congenital myotonic dystrophy. Author(s): Wong LJ, Ashizawa T. Source: American Journal of Human Genetics. 1997 December; 61(6): 1445-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9399912

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Insulin receptor splicing alteration in myotonic dystrophy type 2. Author(s): Savkur RS, Philips AV, Cooper TA, Dalton JC, Moseley ML, Ranum LP, Day JW. Source: American Journal of Human Genetics. 2004 June; 74(6): 1309-13. Epub 2004 April 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15114529

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Insulin regulation of leptin synthesis and secretion in humans: the model of myotonic dystrophy. Author(s): Gomez JM, Molina A, Fernandez-Castaner M, Casamitjana R, MartinezMatos JA, Soler J. Source: Clinical Endocrinology. 1999 May; 50(5): 569-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10468921

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Insulin-like growth factor I circumvents defective insulin action in human myotonic dystrophy skeletal muscle cells. Author(s): Furling D, Marette A, Puymirat J. Source: Endocrinology. 1999 September; 140(9): 4244-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10465298

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Intermolecular and intramolecular interactions regulate catalytic activity of myotonic dystrophy kinase-related Cdc42-binding kinase alpha. Author(s): Tan I, Seow KT, Lim L, Leung T. Source: Molecular and Cellular Biology. 2001 April; 21(8): 2767-78. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11283256

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Intestinal endocrine cells in myotonic dystrophy: an immunocytochemical and computed image analytical study. Author(s): Ronnblom A, Danielsson A, el-Salhy M. Source: Journal of Internal Medicine. 1999 April; 245(4): 91-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10356607

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Intestinal endocrine cells in myotonic dystrophy: an immunocytochemical and computed image analytical study. Author(s): Ronnblom A, Danielsson A, El-Salhy M. Source: Journal of Internal Medicine. 1999 January; 245(1): 91-7. Corrected and Republished In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10095822

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Is it possible to identify infrahissian cardiac conduction abnormalities in myotonic dystrophy by non-invasive methods? Author(s): Babuty D, Fauchier L, Tena-Carbi D, Poret P, Leche J, Raynaud M, Fauchier JP, Cosnay P. Source: Heart (British Cardiac Society). 1999 November; 82(5): 634-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10525524

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Knowledge, views, and experience of 25 women with myotonic dystrophy. Author(s): Faulkner CL, Kingston HM. Source: Journal of Medical Genetics. 1998 December; 35(12): 1020-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9863600

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Laparoscopic cholecystectomy in a patient with myotonic dystrophy. Author(s): Takhar AS, Thaper A, Byrne A, Lobo DN. Source: Journal of the Royal Society of Medicine. 2004 June; 97(6): 284-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15173332

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Late presentation of myotonic dystrophy. Author(s): Clark C, Petty RK, Strong AM. Source: Clinical and Experimental Dermatology. 1998 January; 23(1): 47-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9667115

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Late-onset cytoplasmic body myopathy resembling myotonic dystrophy. Author(s): Morris HR, Landon D, Morgan-Hughes J, Brown P. Source: Muscle & Nerve. 1999 June; 22(6): 781-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10366237

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Left posterior fascicular ventricular tachycardia in myotonic dystrophy. Author(s): Ng KS, Ng WL, Chia BL. Source: International Journal of Cardiology. 2000 June 12; 74(1): 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10912441

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Left ventricular diastolic function in congenital myotonic dystrophy. Author(s): Bu'Lock FA, Sood M, De Giovanni JV, Green SH. Source: Archives of Disease in Childhood. 1999 March; 80(3): 267-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10325709

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Left ventricular hypertrabeculation in myotonic dystrophy type 1. Author(s): Finsterer J, Stollberger C, Wegmann R, Jarius C, Janssen B. Source: Herz. 2001 June; 26(4): 287-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11479941

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Lens epithelial changes and mutated gene expression in patients with myotonic dystrophy. Author(s): Abe T, Sato M, Kuboki J, Kano T, Tamai M. Source: The British Journal of Ophthalmology. 1999 April; 83(4): 452-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10434869

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Leptin after IGF-I generation test in a patient with hypopituitarism and myotonic dystrophy disease. Author(s): Gomez JM, Martinez-Matos JA. Source: Pituitary. 1999; 1(2): 121-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11081190

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Leukocyte CTG repeat length correlates with severity of myotonia in myotonic dystrophy type 1. Author(s): Logigian EL, Moxley RT 4th, Blood CL, Barbieri CA, Martens WB, Wiegner AW, Thornton CA, Moxley RT 3rd. Source: Neurology. 2004 April 13; 62(7): 1081-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15079005

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Localization of myotonic dystrophy protein kinase in human and rabbit tissues using a new panel of monoclonal antibodies. Author(s): Pham YC, Man N, Lam LT, Morris GE. Source: Human Molecular Genetics. 1998 November; 7(12): 1957-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9811941

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Localization of the sites of conduction abnormalities in a mouse model of myotonic dystrophy. Author(s): Saba S, Vanderbrink BA, Luciano B, Aronovitz MJ, Berul CI, Reddy S, Housman D, Mendelsohn ME, Estes NA 3rd, Wang PJ. Source: Journal of Cardiovascular Electrophysiology. 1999 September; 10(9): 1214-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10517654

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Localization of trinucleotide repeat sequences in myotonic dystrophy cells using a single fluorochrome-labeled PNA probe. Author(s): Taneja KL. Source: Biotechniques. 1998 March; 24(3): 472-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9526660

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Long CTG tracts from the myotonic dystrophy gene induce deletions and rearrangements during recombination at the APRT locus in CHO cells. Author(s): Meservy JL, Sargent RG, Iyer RR, Chan F, McKenzie GJ, Wells RD, Wilson JH. Source: Molecular and Cellular Biology. 2003 May; 23(9): 3152-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12697816

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Long CTG.CAG repeats from myotonic dystrophy are preferred sites for intermolecular recombination. Author(s): Pluciennik A, Iyer RR, Napierala M, Larson JE, Filutowicz M, Wells RD. Source: The Journal of Biological Chemistry. 2002 September 13; 277(37): 34074-86. Epub 2002 June 26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12087090

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Long-term follow-up of arrhythmias in patients with myotonic dystrophy treated by pacing: a multicenter diagnostic pacemaker study. Author(s): Lazarus A, Varin J, Babuty D, Anselme F, Coste J, Duboc D. Source: Journal of the American College of Cardiology. 2002 November 6; 40(9): 1645-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12427418

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Loss of catecholaminergic neurons in the medullary reticular formation in myotonic dystrophy. Author(s): Ono S, Takahashi K, Jinnai K, Kanda F, Fukuoka Y, Kurisaki H, Mitake S, Inagaki T, Yamano T, Shimizu N, Nagao K. Source: Neurology. 1998 October; 51(4): 1121-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9781540

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Loss of serotonin-containing neurons in the raphe of patients with myotonic dystrophy: a quantitative immunohistochemical study and relation to hypersomnia. Author(s): Ono S, Takahashi K, Jinnai K, Kanda F, Fukuoka Y, Kurisaki H, Mitake S, Inagaki T, Yamano T, Nagao K. Source: Neurology. 1998 February; 50(2): 535-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9484393

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Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing. Author(s): Charlet-B N, Savkur RS, Singh G, Philips AV, Grice EA, Cooper TA. Source: Molecular Cell. 2002 July; 10(1): 45-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12150906

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Low incidence of myotonic dystrophy in Chinese Hans is associated with a lower number of CTG trinucleotide repeats. Author(s): Sizhong Z, Hui W, Agen P, Cuiying X, Ge Z, Yiping H, Jiayou C. Source: American Journal of Medical Genetics. 2000 June 12; 96(3): 425-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898927

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Lower gastrointestinal tract disturbance in congenital myotonic dystrophy. Author(s): Kerr TP, Robb SA, Clayden GS. Source: European Journal of Pediatrics. 2002 August; 161(8): 468-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12269262

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Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy. Author(s): MacDonald JR, Hill JD, Tarnopolsky MA. Source: Neurology. 2002 December 24; 59(12): 1876-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12499477

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Movement-related cortical potentials in myotonic dystrophy. Author(s): Mitsuoka T, Watanabe C, Kitamura J, Ishigame K, Nakamura S. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 January; 114(1): 99-106. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12495770

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Muscle pathology in 57 patients with myotonic dystrophy type 2. Author(s): Schoser BG, Schneider-Gold C, Kress W, Goebel HH, Reilich P, Koch MC, Pongratz DE, Toyka KV, Lochmuller H, Ricker K. Source: Muscle & Nerve. 2004 February; 29(2): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14755494

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Mutagenic stress modulates the dynamics of CTG repeat instability associated with myotonic dystrophy type 1. Author(s): Pineiro E, Fernandez-Lopez L, Gamez J, Marcos R, Surralles J, Velazquez A. Source: Nucleic Acids Research. 2003 December 1; 31(23): 6733-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14627806

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Myocardial tissue velocity reduction is correlated with clinical neurologic severity in myotonic dystrophy. Author(s): Fung KC, Corbett A, Kritharides L. Source: The American Journal of Cardiology. 2003 July 15; 92(2): 177-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12860220

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Myogenic defects in myotonic dystrophy. Author(s): Amack JD, Mahadevan MS. Source: Developmental Biology. 2004 January 15; 265(2): 294-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14732393

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Myotonic dystrophy and paediatric anaesthesia. Author(s): White RJ, Bass SP. Source: Paediatric Anaesthesia. 2003 February; 13(2): 94-102. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562480

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Myotonic dystrophy and the heart. Author(s): Pelargonio G, Dello Russo A, Sanna T, De Martino G, Bellocci F. Source: Heart (British Cardiac Society). 2002 December; 88(6): 665-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12433913

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Myotonic dystrophy associated with variable circadian rhythms of serum cortisol and isolated thyrotropin deficiency. Author(s): Okumura K, Aso Y, Tayama K, Yoshida N, Takiguchi Y, Takemura Y, Inukai T. Source: The American Journal of the Medical Sciences. 2002 September; 324(3): 158-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12240714

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Myotonic dystrophy type 2. Author(s): Finsterer J. Source: European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies. 2002 September; 9(5): 441-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220374

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Myotonic dystrophy type 2: human founder haplotype and evolutionary conservation of the repeat tract. Author(s): Liquori CL, Ikeda Y, Weatherspoon M, Ricker K, Schoser BG, Dalton JC, Day JW, Ranum LP. Source: American Journal of Human Genetics. 2003 October; 73(4): 849-62. Epub 2003 September 22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14505273

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Myotonic dystrophy: RNA pathogenesis comes into focus. Author(s): Ranum LP, Day JW. Source: American Journal of Human Genetics. 2004 May; 74(5): 793-804. Epub 2004 April 02. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15065017

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Natural history of cardiac involvement in myotonic dystrophy (Steinert's disease): a 13-year follow-up study. Author(s): Mammarella A, Paradiso M, Antonini G, Paoletti V, De Matteis A, Basili S, Donnarumma L, Labbadia G, Di Franco M, Musca A. Source: Adv Ther. 2000 September-October; 17(5): 238-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11186144

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Natural history of cardiac involvement in myotonic dystrophy: correlation with CTG repeats. Author(s): Antonini G, Giubilei F, Mammarella A, Amicucci P, Fiorelli M, Gragnani F, Morino S, Ceschin PV, Fragola PV, Gennarelli M. Source: Neurology. 2000 October 24; 55(8): 1207-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11071501

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New founder haplotypes at the myotonic dystrophy locus in southern Africa. Author(s): Goldman A, Ramsay M, Jenkins T. Source: American Journal of Human Genetics. 1995 June; 56(6): 1373-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7762560

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New genes for old diseases: the molecular basis of myotonic dystrophy and Huntington's disease. The Lumleian Lecture 1995. Author(s): Harper PS. Source: Journal of the Royal College of Physicians of London. 1996 May-June; 30(3): 22131. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8811597

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New methods for molecular diagnosis and demonstration of the (CCTG)n mutation in myotonic dystrophy type 2 (DM2). Author(s): Sallinen R, Vihola A, Bachinski LL, Huoponen K, Haapasalo H, Hackman P, Zhang S, Sirito M, Kalimo H, Meola G, Horelli-Kuitunen N, Wessman M, Krahe R, Udd B. Source: Neuromuscular Disorders : Nmd. 2004 April; 14(4): 274-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019706

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Nondystrophinopathic muscular dystrophies including myotonic dystrophy. Author(s): Nonaka I, Kobayashi O, Osari S. Source: Semin Pediatr Neurol. 1996 June; 3(2): 110-21. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8795845

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Normal coronary arteries and isolated, regional, left ventricular dysfunction in myotonic dystrophy: a case report. Author(s): Doshi SN, Sharma SK, Kim MC. Source: International Journal of Cardiology. 2002 May; 83(2): 191-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12007696

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Normal levels of DM RNA and myotonin protein kinase in skeletal muscle from adult myotonic dystrophy (DM) patients. Author(s): Bhagwati S, Ghatpande A, Leung B. Source: Biochimica Et Biophysica Acta. 1996 December 16; 1317(3): 155-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8988229

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Novel isoform of myotonin protein kinase: gene product of myotonic dystrophy is localized in the sarcoplasmic reticulum of skeletal muscle. Author(s): Shimokawa M, Ishiura S, Kameda N, Yamamoto M, Sasagawa N, Saitoh N, Sorimachi H, Ueda H, Ohno S, Suzuki K, Kobayashi T. Source: American Journal of Pathology. 1997 April; 150(4): 1285-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9094985

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Novel proteins with binding specificity for DNA CTG repeats and RNA CUG repeats: implications for myotonic dystrophy. Author(s): Timchenko LT, Timchenko NA, Caskey CT, Roberts R. Source: Human Molecular Genetics. 1996 January; 5(1): 115-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8789448

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Occlusive hydrocephalus in congenital myotonic dystrophy. Author(s): Rettwitz-Volk W, Wikstroem M, Flodmark O. Source: Brain & Development. 2001 March; 23(2): 122-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11248461

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Ocular motor myotonic phenomenon in myotonic dystrophy. Author(s): Versino M, Colnaghi S, Sandrini G, Cosi V. Source: Annals of the New York Academy of Sciences. 2002 April; 956: 401-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11960825

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Ocular motor myotonic phenomenon in myotonic dystrophy. Author(s): Versino M, Rossi B, Beltrami G, Sandrini G, Cosi V. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 February; 72(2): 23640. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11796775

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Oral sugar clearance and other caries-related factors in patients with myotonic dystrophy. Author(s): Engvall M, Birkhed D. Source: Acta Odontologica Scandinavica. 1997 April; 55(2): 111-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9176659

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Origin of a regressed myotonic dystrophy allele. Author(s): Giordano M, De Angelis MS, Mutani R, Richiardi PM. Source: Journal of Medical Genetics. 1994 February; 31(2): 130-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8182718

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Origin of the expansion mutation in myotonic dystrophy. Author(s): Imbert G, Kretz C, Johnson K, Mandel JL. Source: Nature Genetics. 1993 May; 4(1): 72-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8513329

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Outcome in pregnancies complicated by myotonic dystrophy: a study of 31 patients and review of the literature. Author(s): Rudnik-Schoneborn S, Zerres K. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2004 May 10; 114(1): 44-53. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15099870

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Outcome of pregnancy in women with myotonic dystrophy and analysis of CTG gene expansion. Author(s): Erikson A, Forsberg H, Drugge U, Holmgren G. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 April; 84(4): 416-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7795352

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Overexpression of myotonic dystrophy kinase in BC3H1 cells induces the skeletal muscle phenotype. Author(s): Bush EW, Taft CS, Meixell GE, Perryman MB. Source: The Journal of Biological Chemistry. 1996 January 5; 271(1): 548-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8550617

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Overexpression of myotonic dystrophy protein kinase in C2C12 myogenic culture involved in the expression of ferritin heavy chain and interleukin-1alpha mRNAs. Author(s): Watanabe T, Sasagawa N, Usuki F, Koike H, Saitoh N, Sorimachi H, Maruyama K, Nakase H, Takagi A, Ishiura S, Suzuki K. Source: Journal of the Neurological Sciences. 1999 August 1; 167(1): 26-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10500258

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Pattern and significance of white matter abnormalities in myotonic dystrophy type 1: an MRI study. Author(s): Di Costanzo A, Di Salle F, Santoro L, Tessitore A, Bonavita V, Tedeschi G. Source: Journal of Neurology. 2002 September; 249(9): 1175-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12242535

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Pharyngo-esophageal motility disturbances in patients with myotonic dystrophy. Author(s): Modolell I, Mearin F, Baudet JS, Gamez J, Cervera C, Malagelada JR. Source: Scandinavian Journal of Gastroenterology. 1999 September; 34(9): 878-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10522605

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Polyglandular endocrinopathy in myotonic dystrophy: letter to editor. Author(s): Zargar AH, Bhat MH, Ganie MA, Laway BA, Masoodi SR, Salahuddin M, Kour S. Source: Neurology India. 2002 March; 50(1): 105-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11960166

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Postabsorptive and insulin-stimulated energy and protein metabolism in patients with myotonic dystrophy type 1. Author(s): Perseghin G, Comola M, Scifo P, Benedini S, De Cobelli F, Lanzi R, Costantino F, Lattuada G, Battezzati A, Del Maschio A, Luzi L. Source: The American Journal of Clinical Nutrition. 2004 August; 80(2): 357-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15277156

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Prevalence of myotonic dystrophy in Israeli Jewish communities: inter-community variation and founder premutations. Author(s): Segel R, Silverstein S, Lerer I, Kahana E, Meir R, Sagi M, Zilber N, Korczyn AD, Shapira Y, Argov Z, Abeliovich D. Source: American Journal of Medical Genetics. 2003 June 15; 119A(3): 273-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12784291

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Prevalence of structural cardiac abnormalities in patients with myotonic dystrophy type I. Author(s): Bhakta D, Lowe MR, Groh WJ. Source: American Heart Journal. 2004 February; 147(2): 224-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14760317

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Procainamide for faecal incontinence in myotonic dystrophy. Author(s): Pelliccioni G, Scarpino O, Piloni V. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1999 August; 67(2): 257-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10475766

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Proximal myopathy and diffuse white matter involvement in myotonic dystrophy type I. Author(s): Uluc K, Arsava EM, Erdem S, Tan E. Source: Journal of Neurology. 2002 May; 249(5): 629-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12021957

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Psychosocial impact of predictive testing for myotonic dystrophy type 1. Author(s): Prevost C, Veillette S, Perron M, Laberge C, Tremblay C, Auclair J, Villeneuve J, Tremblay M, Mathieu J. Source: American Journal of Medical Genetics. 2004 April 1; 126A(1): 68-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15039975

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Psychostimulants for hypersomnia (excessive daytime sleepiness) in myotonic dystrophy. Author(s): Annane D, Miller R, Barnes P. Source: Cochrane Database Syst Rev. 2002; (4): Cd003218. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12519589

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Quadriceps strength and timed motor performances in myotonic dystrophy, CharcotMarie-Tooth disease, and healthy subjects. Author(s): Lindeman E, Leffers P, Reulen J, Spaans F, Drukker J. Source: Clinical Rehabilitation. 1998 April; 12(2): 127-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9619654

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Quantification of brain atrophy in patients with myotonic dystrophy and proximal myotonic myopathy: a controlled 3-dimensional magnetic resonance imaging study. Author(s): Kassubek J, Juengling FD, Hoffmann S, Rosenbohm A, Kurt A, Jurkat-Rott K, Steinbach P, Wolf M, Ludolph AC, Lehmann-Horn F, Lerche H, Weber YG. Source: Neuroscience Letters. 2003 September 11; 348(2): 73-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12902021

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Quantitative assessment of speech in myotonic dystrophy. Author(s): Maassen B, ter Bruggen JP, Nanninga-Korver A, van Spaendonck K, WeynBanningh L, Gabreels F. Source: Journal of Neurology. 1995 February; 242(3): 181-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7751865

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Quantitative assessment of the total myocardial uptake ratio of 123I-BMIPP by using the Ishii-MacIntyre method is useful for predicting cardiac complications in patients with mitochondrial encephalomyopathy or myotonic dystrophy. Author(s): Ohkusu Y, Takahashi N, Ishikawa T, Sumita S, Kobayashi T, Matsushita K, Yamakawa Y, Uchino K, Kimura K, Inoue T, Umemura S. Source: Nuclear Medicine Communications. 2003 February; 24(2): 183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12548043

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Quantitative motor assessment in myotonic dystrophy. Author(s): Mathieu J, Boivin H, Richards CL. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 2003 May; 30(2): 129-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12774952

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Quantitative testing of handgrip strength, myotonia, and fatigue in myotonic dystrophy. Author(s): Torres C, Moxley RT, Griggs RC. Source: Journal of the Neurological Sciences. 1983 July; 60(1): 157-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6875612

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Reduction in excess daytime sleepiness by modafinil in patients with myotonic dystrophy. Author(s): Talbot K, Stradling J, Crosby J, Hilton-Jones D. Source: Neuromuscular Disorders : Nmd. 2003 June; 13(5): 357-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798791

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Relation of CTG expansion and clinical variables to electrocardiogram conduction abnormalities and sudden death in patients with myotonic dystrophy. Author(s): Sabovic M, Medica I, Logar N, Mandic E, Zidar J, Peterlin B. Source: Neuromuscular Disorders : Nmd. 2003 December; 13(10): 822-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14678805

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Replication inhibitors modulate instability of an expanded trinucleotide repeat at the myotonic dystrophy type 1 disease locus in human cells. Author(s): Yang Z, Lau R, Marcadier JL, Chitayat D, Pearson CE. Source: American Journal of Human Genetics. 2003 November; 73(5): 1092-105. Epub 2003 October 21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14574643

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Report of the 84th ENMC workshop: PROMM (proximal myotonic myopathy) and other myotonic dystrophy-like syndromes: 2nd workshop. 13-15th October, 2000, Loosdrecht, The Netherlands. Author(s): Moxley RT 3rd, Meola G, Udd B, Ricker K. Source: Neuromuscular Disorders : Nmd. 2002 March; 12(3): 306-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11801405

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Reported relationship between increased CTG repeat lengths in myotonic dystrophy and azoospermia. Author(s): Dean NL, Phillips SJ, Chan P, Tan SL, Ao A. Source: Human Reproduction (Oxford, England). 2002 November; 17(11): 3003-4; Author Reply 3004. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12407064

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Reproductive counselling for women with myotonic dystrophy. Author(s): Magee AC, Hughes AE, Kidd A, Lopez De Munain A, Cobo AM, Kelly K, Dean J, Nevin NC. Source: Journal of Medical Genetics. 2002 March; 39(3): E15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11897835

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Ribonuclear inclusions in skeletal muscle in myotonic dystrophy types 1 and 2. Author(s): Mankodi A, Teng-Umnuay P, Krym M, Henderson D, Swanson M, Thornton CA. Source: Annals of Neurology. 2003 December; 54(6): 760-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14681885

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Right ventricular MR abnormalities in myotonic dystrophy and relationship with intracardiac electrophysiologic test findings: initial results. Author(s): Vignaux O, Lazarus A, Varin J, Coste J, Carlier P, Argaud C, Laforet P, Weber S, Legmann P, Duboc D. Source: Radiology. 2002 July; 224(1): 231-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091688

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RNA leaching of transcription factors disrupts transcription in myotonic dystrophy. Author(s): Ebralidze A, Wang Y, Petkova V, Ebralidse K, Junghans RP. Source: Science. 2004 January 16; 303(5656): 383-7. Epub 2003 December 04. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14657503

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Role of anterior and occipital white matter lesions for smooth eye tracking in myotonic dystrophy. Author(s): Kimmig H, Petrick M, Orszagh M, Mergner T. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2002 June; 72(6): 808-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12023432

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Saccades and smooth pursuit in myotonic dystrophy. Author(s): Shaunak S, Orrell R, Henderson L, Kennard C. Source: Journal of Neurology. 1999 July; 246(7): 600-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10463364

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Severity of cardiac conduction involvement and arrhythmias in myotonic dystrophy type 1 correlates with age and CTG repeat length. Author(s): Groh WJ, Lowe MR, Zipes DP. Source: Journal of Cardiovascular Electrophysiology. 2002 May; 13(5): 444-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12030525

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Sibship stability of genotype and phenotype in myotonic dystrophy. Author(s): Brisson D, Tremblay M, Prevost C, Laberge C, Puymirat J, Mathieu J. Source: Clinical Genetics. 2002 September; 62(3): 220-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12220437

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Signal-averaged electrocardiography in myotonic dystrophy. Author(s): Fragola PV, Calo L, Antonini G, Morino S, Luzi M, De Nardo D, Cannata D. Source: International Journal of Cardiology. 1995 June 2; 50(1): 61-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7558465

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Sleep complaints in patients with myotonic dystrophy. Author(s): Laberge L, Begin P, Montplaisir J, Mathieu J. Source: Journal of Sleep Research. 2004 March; 13(1): 95-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996041

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Slipped (CTG).(CAG) repeats of the myotonic dystrophy locus: surface probing with anti-DNA antibodies. Author(s): Tam M, Erin Montgomery S, Kekis M, Stollar BD, Price GB, Pearson CE. Source: Journal of Molecular Biology. 2003 September 19; 332(3): 585-600. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12963369

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Stapedial reflex in myotonic dystrophy type 1 and CTG repeat expansion. Author(s): Osanai R, Kinoshita M, Hirose K. Source: Journal of Neurology. 2001 December; 248(12): 1056-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12013582

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Structural organization and developmental expression pattern of the mouse WDrepeat gene DMR-N9 immediately upstream of the myotonic dystrophy locus. Author(s): Jansen G, Bachner D, Coerwinkel M, Wormskamp N, Hameister H, Wieringa B. Source: Human Molecular Genetics. 1995 May; 4(5): 843-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7633444

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Subclinical cardiac involvement in myotonic dystrophy manifesting as decreased myocardial Doppler velocities. Author(s): Vinereanu D, Bajaj BP, Fenton-May J, Rogers MT, Madler CF, Fraser AG. Source: Neuromuscular Disorders : Nmd. 2004 March; 14(3): 188-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036328

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Temporomandibular joint and masticatory muscle involvement in myotonic dystrophy: a study by magnetic resonance imaging. Author(s): Zanoteli E, Yamashita HK, Suzuki H, Oliveira AS, Gabbai AA. Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 2002 August; 94(2): 262-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12221397

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Tent-shaped mouth as a presenting symptom of congenital myotonic dystrophy. Author(s): Mashiach R, Rimon E, Achiron R. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 September; 20(3): 312-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12230465

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Testosterone and diurnal rhythmicity of leptin, TNF-alpha and TNF-II receptor in insulin-resistant myotonic dystrophy patients. Author(s): Johansson A, Ahren B, Forsberg H, Olsson T. Source: International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity. 2002 October; 26(10): 1386-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12355336

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The pleiotropic expression of the myotonic dystrophy protein kinase gene illustrates the complex relationships between genetic, biological and clinical covariates of male aging. Author(s): Brisson D, Houde G, St-Pierre J, Vohl MC, Mathieu J, Gaudet D. Source: The Aging Male : the Official Journal of the International Society for the Study of the Aging Male. 2002 December; 5(4): 223-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12630069

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Three cases of androgen-dependent disease associated with myotonic dystrophy. Author(s): Cooper SM, Dawber RP, Hilton-Jones D. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 January; 17(1): 56-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12602971

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Thymoma and myotonic dystrophy: successful treatment with chemotherapy and radiation: case report and review of the literature. Author(s): Kudva GC, Maliekel K, Kim HJ, Naunheim KS, Stolar C, Fletcher JW, Puri S. Source: Chest. 2002 June; 121(6): 2061-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12065378

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Tissue and tumor mosaicism of the myotonin protein kinase gene trinucleotide repeat in a patient with multiple basal cell carcinomas associated with myotonic dystrophy. Author(s): Banuls J, Botella R, Palau F, Ramon R, Diaz C, Paya A, Carnero L, Vergara G. Source: Journal of the American Academy of Dermatology. 2004 February; 50(2 Suppl): S1-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14726854

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Torsion of a non-gravid leiomyomatous uterus in a patient with myotonic dystrophy complaining of acute urinary retention: anaesthetic management for total abdominal hysterectomy. Author(s): Varras M, Polyzos D, Alexopoulos Ch, Pappa P, Akrivis Ch. Source: Clin Exp Obstet Gynecol. 2003; 30(2-3): 147-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12854863

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Transgenic mouse models for myotonic dystrophy type 1 (DM1). Author(s): Wansink DG, Wieringa B. Source: Cytogenetic and Genome Research. 2003; 100(1-4): 230-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526185

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Tumor necrosis factor-alpha and myocardial function in patients with myotonic dystrophy type 1. Author(s): Mammarella A, Ferroni P, Paradiso M, Martini F, Paoletti V, Morino S, Antonini G, Gazzaniga PP, Musca A, Basili S. Source: Journal of the Neurological Sciences. 2002 September 15; 201(1-2): 59-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12163195

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Ultrasound imaging of the masseter muscle in myotonic dystrophy patients. Author(s): Kiliaridis S, Engvall M, Tzakis MG. Source: Journal of Oral Rehabilitation. 1995 August; 22(8): 619-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7472735

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Ultrastructure of muscle spindle in congenital myotonic dystrophy. A study of preterm infant muscle spindles. Author(s): Sahgal V, Sahgal S, Bernes S, Subramani V. Source: Acta Neuropathologica. 1983; 61(3-4): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6228107

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Unstable DNA in a patient with a severe form of congenital myotonic dystrophy. Author(s): Tachi N, Ohya K, Chiba S, Sato T. Source: Journal of the Neurological Sciences. 1993 November; 119(2): 180-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8277332

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Unstable DNA may be responsible for the incomplete penetrance of the myotonic dystrophy phenotype. Author(s): Shelbourne P, Winqvist R, Kunert E, Davies J, Leisti J, Thiele H, Bachmann H, Buxton J, Williamson B, Johnson K. Source: Human Molecular Genetics. 1992 October; 1(7): 467-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1307246

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Unstable DNA sequence in myotonic dystrophy. Author(s): Harley HG, Rundle SA, Reardon W, Myring J, Crow S, Brook JD, Harper PS, Shaw DJ. Source: Lancet. 1992 May 9; 339(8802): 1125-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1349364

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Unusual clinical findings and Complex III deficiency in a family with myotonic dystrophy. Author(s): Seijo-Martinez M, Castro del Rio M, Campos Y, Palau F, Arenas J, Teijeira S, Fernandez Hojas R, Navarro C. Source: Journal of the Neurological Sciences. 2003 April 15; 208(1-2): 87-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12639730

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Unusual fetal movement in congenital myotonic dystrophy. Author(s): Hsu CD, Feng TI, Crawford TO, Johnson TR. Source: Fetal Diagnosis and Therapy. 1993 May-June; 8(3): 200-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8240694

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Use of an insertable loop recorder in a myotonic dystrophy patient. Author(s): Hadian D, Lowe MR, Scott LR, Groh WJ. Source: Journal of Cardiovascular Electrophysiology. 2002 January; 13(1): 72-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11843487

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Use of variable simple sequence motifs as genetic markers: application to study of myotonic dystrophy. Author(s): Smeets HJ, Brunner HG, Ropers HH, Wieringa B. Source: Human Genetics. 1989 October; 83(3): 245-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2571562

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Usefulness of chromosome 19 RFLP haplotypes in the diagnosis of myotonic dystrophy. Author(s): Nokelainen PT, Alanen-Kurki L, Somer HV, Pihko SH, Peltonen L. Source: Muscle & Nerve. 1991 May; 14(5): 451-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1678492

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Value of the electrocardiogram in determining cardiac events and mortality in myotonic dystrophy. Author(s): Colleran JA, Hawley RJ, Pinnow EE, Kokkinos PF, Fletcher RD. Source: The American Journal of Cardiology. 1997 December 1; 80(11): 1494-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9399734

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Variants of myotonic dystrophy in pre-adolescent life (the syndrome of myotonic dysembryoplasia). Author(s): Pruzanski W. Source: Brain; a Journal of Neurology. 1966 September; 89(3): 563-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5950778

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Vascular adrenergic receptor responses in skeletal muscle in myotonic dystrophy. Author(s): Mechler F, Mastaglia FL. Source: Annals of Neurology. 1981 February; 9(2): 157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7235630

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Vascular tufts at the pupillary margin in myotonic dystrophy. Author(s): Cobb B, Shilling JS, Chisholm IH. Source: American Journal of Ophthalmology. 1970 April; 69(4): 573-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=5437822

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Velopharyngeal incompetence as the presenting symptom of myotonic dystrophy. Author(s): Salomonson J, Kawamoto H, Wilson L. Source: Cleft Palate J. 1988 July; 25(3): 296-300. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3168273

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Ventricular late potentials in myotonic dystrophy. Author(s): Milner MR, Hawley RJ, Jachim M, Lindsay J Jr, Fletcher RD. Source: Annals of Internal Medicine. 1991 October 15; 115(8): 607-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1892332

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Ventricular tachycardia and sudden death in myotonic dystrophy. Author(s): Hiromasa S, Ikeda T, Kubota K, Hattori N, Coto H, Maldonado C, Kupersmith J. Source: American Heart Journal. 1988 April; 115(4): 914-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3354423

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Ventricular tachycardia and sudden death in myotonic dystrophy: clinical, electrophysiologic and pathologic features. Author(s): Grigg LE, Chan W, Mond HG, Vohra JK, Downey WF. Source: Journal of the American College of Cardiology. 1985 July; 6(1): 254-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4008782

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Viral vector producing antisense RNA restores myotonic dystrophy myoblast functions. Author(s): Furling D, Doucet G, Langlois MA, Timchenko L, Belanger E, Cossette L, Puymirat J. Source: Gene Therapy. 2003 May; 10(9): 795-802. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12704419

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Visualization of double-stranded RNAs from the myotonic dystrophy protein kinase gene and interactions with CUG-binding protein. Author(s): Michalowski S, Miller JW, Urbinati CR, Paliouras M, Swanson MS, Griffith J. Source: Nucleic Acids Research. 1999 September 1; 27(17): 3534-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10446244

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Warm heart operation in a patient with myotonic dystrophy. Author(s): Sakai T, Miki S, Ueda Y, Nomoto T, Hashimoto S, Takahashi K. Source: The Annals of Thoracic Surgery. 1996 October; 62(4): 1203-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8823122

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Whole body insulin resistance in myotonic dystrophy. Author(s): Moxley RT, Corbett AJ, Minaker KL, Rowe JW. Source: Annals of Neurology. 1984 February; 15(2): 157-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6367619

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CHAPTER 2. NUTRITION AND MYOTONIC DYSTROPHY Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and myotonic dystrophy.

Finding Nutrition Studies on Myotonic Dystrophy The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “myotonic dystrophy” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “myotonic dystrophy” (or a synonym): •

Anaesthesia for caesarean section in a patient with myotonic dystrophy receiving warfarin therapy. Author(s): Department of Anaesthesia, Aberdeen Royal Hospitals NHS Trust, Foresterhill, Scotland. Source: Campbell, A M Thompson, N Can-J-Anaesth. 1995 May; 42(5 Pt 1): 409-14 0832610X

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CBKLP, a protein similar to the human myotonic dystrophy kinase, is essential for normal morphogenesis in Saccharomyces cerevisiae. Source: Racki, W.J. Becam, A.M. Nasr, F. Herbert, C.J. EMBO-j. Oxford, U.K.: Oxford University Press. Sept 1, 2000. volume 19 (17) page 4524-4532. 0261-4189

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Platelet functions, alpha 2-adrenergic receptors and cytoplasmic free calcium are normal in the myotonic dystrophy of Steinert. Source: Lanza, F Cazenave, J P Hemmendinger, S Stierle, A Tranchant, C Warter, J M JNeurol-Sci. 1987 June; 79(1-2): 13-22 0022-510X

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Potential involvement of ubiquinone in myotonic dystrophy pathophysiology: new diagnostic approaches for new rationale therapeutics. Author(s): Department of Veterinary, Anatomy, Biochemistry and Physiology, Faculty of Veterinary Medicine, University of Pisa, Viale delle Piagge 2, I-56124 Pisa, Italy. Source: Tedeschi, D Lombardi, V Mancuso, M Martelli, F Sighieri, C Rocchi, A Tovani, S Siciliano, G Murri, L Neurol-Sci. 2000; 21(5 Suppl): S979-80 1590-1874

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

•

The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

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Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND MYOTONIC DYSTROPHY Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to myotonic dystrophy. 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 myotonic dystrophy 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 “myotonic dystrophy” (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 myotonic dystrophy: •

A study of the facilitation of respiration in myotonic dystrophy. Author(s): Nitz J, Burke B. Source: Physiotherapy Research International : the Journal for Researchers and Clinicians in Physical Therapy. 2002; 7(4): 228-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12528578

•

Anaesthesia for caesarean section in a patient with myotonic dystrophy receiving warfarin therapy. Author(s): Campbell AM, Thompson N. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1995 May; 42(5 Pt 1): 409-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7614649

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Creatine monohydrate in DM2/PROMM: a double-blind placebo-controlled clinical study. Proximal myotonic myopathy. Author(s): Schneider-Gold C, Beck M, Wessig C, George A, Kele H, Reiners K, Toyka KV. Source: Neurology. 2003 February 11; 60(3): 500-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12578937

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Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1. Author(s): Tarnopolsky M, Mahoney D, Thompson T, Naylor H, Doherty TJ. Source: Muscle & Nerve. 2004 January; 29(1): 51-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694498

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De novo myotonic dystrophy mutation in a Nigerian kindred. Author(s): Krahe R, Eckhart M, Ogunniyi AO, Osuntokun BO, Siciliano MJ, Ashizawa T. Source: American Journal of Human Genetics. 1995 May; 56(5): 1067-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7726160

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Dystrophia myotonica: a case report. Author(s): Hart JF. Source: Journal of Manipulative and Physiological Therapeutics. 1987 December; 10(6): 338. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3437242

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Dystrophia myotonica: a case report. Author(s): Zahid MA, Washington G. Source: Journal of Manipulative and Physiological Therapeutics. 1987 February; 10(1): 21-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3559422

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Event-related potentials (P300) in myotonic dystrophy. Author(s): Hanafusa H, Motomura N, Asaba H, Sakai T, Kawamura H. Source: Acta Neurologica Scandinavica. 1989 August; 80(2): 111-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2816271

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Letter: Exacerbation of myotonia dystrophica by vincristine. Author(s): Michalak JC, Dibella NJ. Source: The New England Journal of Medicine. 1976 July 29; 295(5): 283. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=934199

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Membership of a patients' association and well-being. A study into the relationship between membership of a patients' association, fellow-patient contact, information received, and psychosocial well-being of people with a neuromuscular disease.

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Author(s): van Haastregt JC, de Witte LP, Terpstra SJ, Diederiks JP, van der Horst FG, de Geus CA. Source: Patient Education and Counseling. 1994 October; 24(2): 135-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7746763 •

Membrane defects in Duchenne dystrophy: protease affecting sarcoplasmic reticulum. Author(s): Nagy B, Samaha FJ. Source: Annals of Neurology. 1986 July; 20(1): 50-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3527039

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Myotonic dystrophy: an electrophysiological study of cognitive deficits. Author(s): Ragazzoni A, Pinto F, Taiuti R, Silveri MC. Source: The Canadian Journal of Neurological Sciences. Le Journal Canadien Des Sciences Neurologiques. 1991 August; 18(3): 300-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1913364

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Neural control of the expression of a Ca(2+)-activated K+ channel involved in the induction of myotonic-like characteristics. Author(s): Ramirez BU, Behrens MI, Vergara C. Source: Cellular and Molecular Neurobiology. 1996 February; 16(1): 39-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8714558

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Neurological disorders with autosomal dominant transmission. Author(s): Simpson JM. Source: J Neurosurg Nurs. 1984 October; 16(5): 262-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6239015

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Phenytoin and membrane fluidity in myotonic dystrophy. Author(s): Roses AD, Butterfield A, Appel SH, Chestnut DB. Source: Archives of Neurology. 1975 August; 32(8): 535-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=168843

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Pursed lips breathing improves ventilation in myotonic muscular dystrophy. Author(s): Ugalde V, Breslin EH, Walsh SA, Bonekat HW, Abresch RT, Carter GT. Source: Archives of Physical Medicine and Rehabilitation. 2000 April; 81(4): 472-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10768538

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Spontaneous chromosome loss and colcemid resistance in lymphocytes from patients with myotonic dystrophy type 1. Author(s): Casella M, Lucarelli M, Simili M, Beffy P, Del Carratore R, Minichilli F, Chisari C, Simi S.

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Source: Cytogenetic and Genome Research. 2003; 100(1-4): 224-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14526184 •

Swedish views on selenium. Author(s): Bruce A. Source: Ann Clin Res. 1986; 18(1): 8-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3717875

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The changes in muscle strength and relaxation time after a comprehensive rehabilitation program for patients with myotonic dystrophy. Author(s): Moon JH, Na YM, Kang SW, Lee HS. Source: Yonsei Medical Journal. 1996 August; 37(4): 237-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8942293

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The clinical effects of Ganoderma lucidum spore preparations in 10 cases of atrophic myotonia. Author(s): Fu HD, Wang ZY. Source: J Tradit Chin Med. 1982 March; 2(1): 63-5. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6765691

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

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General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. PATENTS ON MYOTONIC DYSTROPHY Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “myotonic dystrophy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on myotonic dystrophy, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Myotonic Dystrophy By performing a patent search focusing on myotonic dystrophy, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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The following is an example of the type of information that you can expect to obtain from a patent search on myotonic dystrophy: •

Diagnosis of myotonic muscular dystrophy Inventor(s): Caskey; C. Thomas (West University, TX), Fenwick; Raymond G. (Sugarland, TX), Friedman; David L. (Houston, TX), Fu; Ying-Hui (Columbus, OH), Pizzuti; Antonio (Milan, IT) Assignee(s): Baylor College of Medicine (Houston, TX) Patent Number: 5,552,282 Date filed: June 6, 1993 Abstract: The present invention includes a DNA clone from the myotonic muscular dystrophy gene, a cosmid probe to the myotonic dystrophy site, as well as methods of detecting myotonic muscular dystrophy using RFLP. The method involves the steps of digesting DNA from an individual to be tested with a restriction endonuclease and detecting the restriction fragment length polymorphism with hybridization to probes within the myotonic muscular locus and southern blot analysis. Alternatively, the myotonic muscular dystrophy gene can be measured by determining the amount of mRNA or measuring the amount of protein with an antibody. Further, the myotonic muscular dystrophy gene defect can be detected using either fluorescence in situ hybridization or pulsed field gel electrophoresis using the probes described herein. Excerpt(s): This invention relates to the field of molecular diagnosis of myotonic muscular dystrophy. The myotonic muscular dystrophy (DM) disease is the most common adult muscular dystrophy in man with a prevalence of 1 in 10,000. The disorder is inherited in an autosomal dominant manner with variable expression of symptoms from individual to individual within a given family. Furthermore, the phenomenon of anticipation (increasing disease severity over generations) is well documented for DM. This is particularly evident when an affected mother transmits the gene for the disease to her offspring. These offspring have a high incidence of mental retardation and profound infantile myotonia. Adult patients with DM manifest a pleiotropic set of symptoms including myotonia, cardiac arrhythmias, cataracts, frontal baldness, hypogonadism, and other endocrine dysfunctions. There is no evidence that myotonic muscular dystrophy may be caused by defects in more than one gene. A myotonic muscular dystrophy gene has been mapped to human chromosome position 19q13.3. Both a genetic and physical map of the region was developed by a group of investigators acting as a voluntary consortium under sponsorship of the Muscular Dystrophy Association. The genetic linkage studies identified two RFLP alleles, D10 and X75, which are polymerase chain reaction (PCR)-based dinucleotide polymorphisms and are tightly linked to DM. Web site: http://www.delphion.com/details?pn=US05552282__

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•

DNA sequence encoding the myotonic dystrophy gene and uses thereof Inventor(s): Brook; J. David (West Bridgford, GB), Harley; Helen G. (Rhiwbina, GB), Housman; David E. (Newton, MA), Johnson; Keith J. (Glasgow, GB), Shaw; Duncan J. (Banchory, GB) Assignee(s): Massachusetts Institute of Technology (Cambridge, MA), University of Wales College of Medicine (Cardiff, GB) Patent Number: 5,977,333 Date filed: April 14, 1995 Abstract: A nucleotide sequence, specifically a CTG triplet repeat, is shown to be expanded in individuals affected with myotonic dystrophy and can be identified in a sample obtained from an individual. Individuals in whom the CTG triplet repeat is present in normal copy number are likely to be minimally affected and individuals in whom the CTG triplet repeat occurs in abnormally high copy number are likely to be more severely affected. Excerpt(s): Myotonic dystrophy (DM) is an autosomal dominant neuromuscular disease with an estimated minimum incidence of 1 in 8000 (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). It is the most common form of muscular dystrophy affecting adults. The clinical picture in DM is well established but exceptionally variable (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). Although generally considered a disease of muscle, with myotonia, progressive weakness and wasting, DM is characterized by abnormalities in a variety of other systems. DM patients often suffer from cardiac conduction defects, smooth muscle involvement, hypersomnia, cataracts, abnormal glucose response, and, in males, premature balding and testicular atrophy (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). One of the striking features of this disorder is the variability of phenotype, both within and between families. For clinical purposes, patients are often subdivided into three groups according to the clinical syndrome and age at onset of the disorder (Harper, P. S. and Dyken, P. R., Lancet, 2:53-55 (1972)). The mildest form, which is occasionally difficult to diagnose, is seen in middle or old age and is characterized by cataracts with little or no muscle involvement. The classical form, showing myotonia and muscle weakness, most frequently has onset in early adult life and in adolescence. The most severe form, which occurs congenitally, is associated with generalized muscular hypoplasia, mental retardation, and high neonatal mortality. Those congenitally affected offspring surviving the neonatal period invariably exhibit the classical form of the disease in late childhood or adolescence. The congenital form of DM is almost exclusively maternally transmitted. The phenomenon of anticipation (Howeler, C. J. et al., Brain, 112:779-797 (1989)), in which the disease symptoms become more severe and age at onset earlier in successive generations, is often most strikingly manifested in a family producing a congenitally affected child. To date this disease has been untreatable and its biochemical basis is not understood. Biochemical studies have failed to identify the defective protein in myotonic dystrophy, although several have implicated defects in membrane structure and function (Harper, P. S., Myotonic Dystrophy, 2nd ed., W. B. Saunders Co., London, 1989). Abnormalities in calcium transport (Seiler, D. and Kuhn, E., Schweitz Med. Wochenschr. 100:1374-1376 (1970)), membrane fluidity (Butterfield, D. A. et al., Biochemistry, 13:5078-5082 (1974)), sodiumpotassium ATPase stoichiometry (Hull, K. L., Jr. and Roses, A. D., J. Physiol., 254:169181 (1976)), and apamin receptor expression (Renaud, J. F. et al., Nature 319:676-680 (1986)) have all been reported for DM. There is also evidence of reduced phosphorylation of membrane proteins in both red blood cells (Roses, A. D. and Appel,

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S. H., Proc. Natl. Acad. Sci. USA 70:1855-1859 (1973)) and sarcolemmal membranes from muscle biopsies of patients (Roses, A. D. and Appel, S. H., Nature 250:245-247 (1974)). A better understanding of the underlying mechanism of DM would be very valuable in diagnosing and, ultimately, treating or preventing DM. Web site: http://www.delphion.com/details?pn=US05977333__ •

Remedy for myotonic dystrophy Inventor(s): Endo; Tomio (Nishinomiya, JP), Ohsawa; Nakaaki (Osaka, JP), Sugino; Masakazu (Osaka, JP) Assignee(s): Kanebo Ltd. (Tokyo, JP) Patent Number: 5,834,451 Date filed: April 15, 1997 Abstract: A remedy for myotonic dystrophy, containing dehydroepiandrosterone sulfate or a pharmacologically acceptable salt thereof, being efficacious for myotonia, adynamia and amyotrophy, and having a high safety. Excerpt(s): This application is a 371 of PCT/JP95/01561 filed Aug. 7, 1995. The present invention relates to a remedy efficacious for symptomatic improvement in myotonic dystrophy and various other diseases manifesting myotonia. Myotonic dystrophy (hereinafter referred to sometimes as MyD) is an autosomal-dominant hereditary disease caused by abnormalities of the long arm of chromosome 19 and its morbidity is said to be 4 to 5 in 100,000. MyD is a degenerative disease, the cardinal symptoms of which are muscular atrophy and decreased muscle strength dominantly found in muscles of the face and neck and in distal muscles of the limbs, and appearance of repetitive muscle cell membrane action potentials in skeletal muscles on contraction and consequent delays in relaxation (myotonia), and which is complicated by multiple organ disorders. Web site: http://www.delphion.com/details?pn=US05834451__

Patent Applications on Myotonic Dystrophy As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to myotonic dystrophy: •

13245, a novel human myotonic dystrophy type protein kinase and uses therefor Inventor(s): Kapeller-Libermann, Rosana; (Chestnut Hill, MA) Correspondence: Akin, Gump, Strauss, Hauer & Feld, L.L.P.; One Commerce Square; 2005 Market Street, Suite 2200; Philadelphia; PA; 19103; US Patent Application Number: 20020160483 Date filed: October 23, 2001

9

This has been a common practice outside the United States prior to December 2000.

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Abstract: The invention provides isolated nucleic acids molecules, designated 13245 nucleic acid molecules, which encode a novel myotonic dystrophy type protein kinase. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 13245 nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a 13245 gene has been introduced or disrupted. The invention still further provides isolated 13245 proteins, fusion proteins, antigenic peptides and anti-13245 antibodies. Diagnostic methods utilizing compositions of the invention are also provided. Excerpt(s): This application is entitled to priority pursuant to 35 U.S.C.sctn.119(e) to U.S. provisional patent application 60/242,429 which was filed on Oct. 23, 2000. Protein phosphorylation, for example at serine, threonine, and tyrosine residues, is a key regulatory mechanism for a variety of cellular processes. Protein phosphorylation is influenced primarily by enzymes of two types, namely protein kinases (PKs) and protein phosphatases (PPs). PKs catalyze addition of a phosphate moiety to a protein amino acid residue (generally a serine, threonine, or tyrosine residue), and PPs catalyze removal of such moieties. The catalytic activities of PKs and PPs are, in turn, influenced by the state of the cell and the environment in which it finds itself. Myotonic dystrophy type PKs (MDPKs) are associated with modulation of cell morphology, shape, and contractility. MDPKs are also known to modulate the activity of skeletal muscle voltagegated sodium channels, but not cardiac muscle voltage-gated sodium channels. MDPKs thus have a role in a variety of musculodegenerative and other musculoskeletal disorders including, for example, muscular dystrophy (MD) of various types (e.g., Duchenne's MD, limb-girdle MD, Becker MD, facioscapulohumerol MD, mitochondrial myopathy, and congenital myopathy) and myotonic dystrophies (e.g., Steinert's disease and Thomsen's disease). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions, organisms and methodologies employing a novel human kinase Inventor(s): Liu, Wei; (Sudbury, MA), Wu, Leeying; (Lexington, MA) Correspondence: Nixon Peabody, Llp; 401 9th Street, NW; Suite 900; Wasington; DC; 20004-2128; US Patent Application Number: 20040121383 Date filed: November 7, 2003 Abstract: This invention provides compositions, organisms and methodologies employing a novel human protein kinase, MCRK1. The novel human kinase has sequence homology to rat myotonic dystrophy kinase-related Cdc42 binding kinase (MRCK) alpha. The gene encoding the novel kinase is localized in locus 11q13 of human chromosome 11. The novel protein kinase comprises multiple functional/structural domains that include a kinase domain, a pkinase_C domain, a DAG-PE binding domain, and a CNH domain. The sequence and structure similarity between the novel human protein and rat MRCK alpha indicates that the novel human protein may function as a downstream effector of Cdc42 in cytoskeleton reorganization. Excerpt(s): The present invention relates to compositions, organisms and methodologies employing a novel human protein kinase, MRCK1, which has 65% sequence homology to rat myotonic dystrophy kinase-related Cdc42 binding kinase (MRCK). This invention can be used for diagnosing, prognosing and treating kinase-related diseases and, in particular, diseases associated with aberrant expression of MRCK1. Protein kinases

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regulate many different cell proliferation, differentiation, and signaling processes by adding phosphate groups to proteins. Uncontrolled signaling has been implicated in a variety of disease conditions including inflammation, cancer, arteriosclerosis, and psoriasis. Reversible protein phosphorylation is the main strategy for controlling activities of eukaryotic cells. It is estimated that more than 1,000 of the 10,000 proteins active in a typical mammalian cell are phosphorylated. As is well known in the art, the high energy phosphate, which drives activation, is generally transferred from adenosine triphosphate molecules (ATP) to a particular protein by protein kinases and removed from that protein by protein phosphatases. Phosphorylation occurs in response to extracellular signals (hormones, neurotransmitters, growth and differentiation factors, etc.), cell cycle checkpoints, and environmental or nutritional stresses. The phosphorylation process is roughly analogous to turning on a molecular switch. When the switch goes on, the appropriate protein kinase activates a metabolic enzyme, regulatory protein, receptor, cytoskeletal protein, ion channel or pump, or transcription factor. The kinases comprise the largest known protein group, a superfamily of enzymes with widely varied functions and specificities. They are usually named after their substrate, their regulatory molecules, or some aspect of a mutant phenotype. With regard to substrates, the protein kinases may be roughly divided into two groups: those that phosphorylate tyrosine residues (protein tyrosine kinases, PTK) and those that phosphorylate serine or threonine residues (serine/threonine kinases, STK). A few protein kinases have dual specificity and phosphorylate threonine and tyrosine residues. Almost all kinases contain a similar 250-300 amino acid catalytic domain. The primary structure of the kinase domains is conserved and can be further subdivided into 11 subdomains. The N-terminal of the kinase domain, which contains subdomains I-IV, generally folds into a lobe-like structure that binds and orients the ATP (or GTP) donor molecule. The C terminal of the kinase domain forms a larger lobe, which contains subdomains VI-XI, binds the protein substrate and carries out the transfer of the gamma phosphate from ATP to the hydroxyl group of a serine, threonine, or tyrosine residue. Subdomain V spans the two lobes. Each of the 11 subdomains contains specific residues and motifs or patterns of amino acids that are characteristic of that subdomain and are highly conserved. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Intron associated with myotonic dystrophy type 2 and methods of use Inventor(s): Day, John W.; (Minneapolis, MN), Liquori, Christina; (Minneapolis, MN), Ranum, Laura P.W.; (St. Paul, MN) Correspondence: Mueting, Raasch & Gebhardt, P.A.; P.O. Box 581415; Minneapolis; MN; 55458; US Patent Application Number: 20030108887 Date filed: May 10, 2002 Abstract: The present invention provides methods for identifying individuals not at risk for developing myotonic dystrophy type 2 (DM2), and individuals that have or at risk for developing DM2. The present invention also provides isolated polynucleotides that include a repeat tract within intron 1 of the zinc finger protein 9. Excerpt(s): This application claims the benefit of U.S. Provisional Application Serial No. 60/290,365, filed May 11, 2001, U.S. Provisional Application Serial No. 60/302,022, filed Jun. 29, 2001, and U.S. Provisional Application Serial No. 60/337,831, filed Nov. 13, 2001, which are incorporated by reference herein. DM is a dominantly-inherited,

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multisystemic disease with a consistent constellation of seemingly unrelated and rare clinical features including: myotonia, muscular dystrophy, cardiac conduction defects, posterior iridescent cataracts, and endocrine disorders (Harper, Myotonic Dystrophy, W. B. Saunders, London, ed. 2, 1989)). DM was first described nearly 100 years ago, but the existence of more than one genetic cause was only recognized after genetic testing became available for myotonic dystrophy type 1 (DM1) (Thornton et al., Ann. Neurology, 35, 269 (1994), Ricker et al., Neurology, 44, 1448 (1994)). DM1 is caused by an expanded CTG repeat on chromosome 19 that is both in the 3' untranslated region of the dystrophia myotonica-protein kinase (DMPK) gene, and in the promoter region of the immediately adjacent homeodomain gene SIX5 (Groenen and Wieringa, Bioessays, 20, 901 (1998), Tapscott, Science, 289, 1701 (2000)). How the CTG expansion in a noncoding region of a gene causes the complex DM phenotype remains unclear. Suggested mechanisms include: (i) haploinsufficiency of the DMPK protein; (ii) altered expression of neighboring genes, including SIX5; and (iii) pathogenic effects of the CUG expansion in RNA which accumulates as nuclear foci and disrupts cellular function. Several mouse models have developed different aspects of DM1: a model expressing mRNA with CUG repeats manifests myotonia and the myopathic features of DM1; a DMPK knockout has cardiac abnormalities; and SIX5 knockouts have cataracts. Taken together, these data have been interpreted to suggest that each theory may contribute to DM1 pathogenesis and that DM1 may be a regional gene disorder. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel isoform of myotonic dystrophy associated protein kinase and uses thereof Inventor(s): Mahadevan, Mani S.; (Madison, WI), Tiscornia, Gustavo; (Madison, WI) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020061571 Date filed: March 20, 2001 Abstract: The invention provides a novel DMPK isoform, isolated and purified RNA encoding the novel isoform, and methods of detecting the novel isoform, e.g., to predict disease outcome or detect disease. Excerpt(s): This application claims priority from U.S. provisional application No. 60/190,590, filed Mar. 20, 2000. Myotonic dystrophy (DM) is an autosomal dominant inherited neuromuscular disorder with a global incidence of 1 per 8000 (Harper, 1989). There are two distinct forms, an adult onset and a congenital form of DM. Adult onset DM is primarily characterized by myotonia, muscle weakness and wasting. However, it also affects a number of organ systems resulting in cataracts, cardiac conduction abnormalities, testicular atrophy, male pattern baldness and insulin resistance. Hypotonia, mental retardation, delayed muscle maturation and developmental abnormalities characterize congenital DM, the most severe form of the disease. The DM mutation was identified as an expansion of a CTG triplet repeat in the 3' untranslated region (3'UTR) of a gene encoding a serine-threonine protein kinase (DMPK) (Brook et al., 1992; Fu et al., 1992; Mahadevan et al., 1992). The DM mutation was one of the first "triplet repeat" mutations identified. Although it has been eight years since its discovery, the DM mutation is one of the most notable enigmas in human genetics. Given the location of the (CTG).sub.n in the 3' untranslated region of the DM protein kinase (DMPK) gene, it has been difficult to reconcile the dominant nature of the DM mutation (a single copy causes a phenotype in carrying individuals).

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with myotonic dystrophy, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “myotonic dystrophy” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on myotonic dystrophy. You can also use this procedure to view pending patent applications concerning myotonic dystrophy. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. BOOKS ON MYOTONIC DYSTROPHY Overview This chapter provides bibliographic book references relating to myotonic dystrophy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on myotonic dystrophy include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Chapters on Myotonic Dystrophy In order to find chapters that specifically relate to myotonic dystrophy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and myotonic dystrophy using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “myotonic dystrophy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on myotonic dystrophy: •

Myotonic Dystrophy: Steinert Muscular Dystrophy, Dytrophia Myotonica Source: in Plumridge, D., et al., eds. Student with a Genetic Disorder: Educational Implications for Special Education Teachers and for Physical Therapists, Occupational Therapists, and Speech Pathologists. Springfield, IL: Charles C Thomas Publisher. 1993. p. 186-191. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (217) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393. Summary: Myotonic dystrophy is a type of muscular dystrophy that affects other parts of the body in addition to muscles. This chapter on myotonic dystrophy is from a text for special education teachers, physical therapists, occupational therapists, and speech pathologists on the educational implications of genetic disorders. Topics covered

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include the physical and characteristic features of the disorder, the genetics of the disorder, the cognitive and behavior profiles, the educational implications, physical therapy, occupational therapy, hearing and speech considerations, psychosocial issues, and prognosis. 6 references.

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CHAPTER 6. PERIODICALS AND NEWS ON MYOTONIC DYSTROPHY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover myotonic dystrophy.

News Services and Press Releases One of the simplest ways of tracking press releases on myotonic dystrophy is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “myotonic dystrophy” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to myotonic dystrophy. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “myotonic dystrophy” (or synonyms). The following was recently listed in this archive for myotonic dystrophy: •

Cellular Effects Of Myotonic Dystrophy Mutation Becoming Clearer Source: Reuters Medical News Date: May 04, 1998

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The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “myotonic dystrophy” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “myotonic dystrophy” (or synonyms). If you know the name of a company that is relevant to myotonic dystrophy, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “myotonic dystrophy” (or synonyms).

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Academic Periodicals covering Myotonic Dystrophy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to myotonic dystrophy. In addition to these sources, you can search for articles covering myotonic dystrophy that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

These publications are typically written by one or more of the various NIH Institutes.

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

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National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

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Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

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NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

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Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

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Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

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Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

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

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “myotonic dystrophy” (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 3611 26 324 1 79 4041

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “myotonic dystrophy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

The Genome Project and Myotonic Dystrophy In the following section, we will discuss databases and references which relate to the Genome Project and myotonic dystrophy. 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).21 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. 18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process. 21 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.

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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “myotonic dystrophy” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for myotonic dystrophy: •

Protein Kinase, Serine/threonine, Related to the Myotonic Dystrophy Protein Kinase Web site: http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=603412 Genes and Disease (NCBI - Map)

The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •

Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html

•

Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html

•

Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html

•

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

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•

Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html

•

Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez

Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •

3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books

•

Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome

•

NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/

•

Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide

•

OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM

•

PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset

•

ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo

•

Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein

•

PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed

•

Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure

•

Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy

To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then

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select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “myotonic dystrophy” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database22 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 Database23 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis. To access the GDB, simply go to the following hyperlink: http://www.gdb.org/. Search “All Biological Data” by “Keyword.” Type “myotonic dystrophy” (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).

22

Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 23 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on myotonic dystrophy can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to myotonic dystrophy. 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 myotonic dystrophy. 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 “myotonic dystrophy”:

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Charcot-Marie-Tooth Disease http://www.nlm.nih.gov/medlineplus/charcotmarietoothdisease.html Muscle Disorders http://www.nlm.nih.gov/medlineplus/muscledisorders.html Muscular Dystrophy http://www.nlm.nih.gov/medlineplus/musculardystrophy.html Neurologic Diseases http://www.nlm.nih.gov/medlineplus/neurologicdiseases.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on myotonic dystrophy. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Myotonic Dystrophy Source: in DeFeo, A.B., ed. Parent Articles 2. San Antonio, TX: Communication Skill Builders. 1995. p. 153-154. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; Fax (800) 232-1223. PRICE: $55.00 plus shipping and handling. Order Number 076-163-0732. Summary: This fact sheet, from a communication skills book for parents, provides information on myotonic dystrophy, an inherited disease that involves increasing weakness of the muscles that control movement. Topics covered include general information about myotonic dystrophy, the effects on speech including speech breathing and voice, resonance, articulation, and swallowing, and associated difficulties that may impact language, including mental retardation, frequent hospitalization, motor impairment, and inadequate social skills. The author provides detailed suggestions for parent-child interaction, including recommended activities. 1 reference.

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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to myotonic dystrophy. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Associations and Myotonic Dystrophy The following is a list of associations that provide information on and resources relating to myotonic dystrophy: •

International Myotonic Dystrophy Organization Telephone: (818) 951-2311 Toll-free: (866) 679-7954 Fax: (818) 352-0096 Email: [email protected] and [email protected] Web Site: http://www.myotonicdystrophy.org Background: The International Myotonic Dystrophy Organization, Inc., (IMDO) functions on an international basis, supporting patients with information and services

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worldwide. The organization assists patients and their families with their problems via the toll-free helpline and/or e-mail and mail. IMDO has a very informative website, publishes a monthly e-newsletter, offers Medical Alert cards and some educational materials,and facilitates support groups as well as Pen Pals via e-mail. The organization provides referrals and reference information to the public and professionals, promotes collaborative research and disseminates research information. The International Myotonic Dystrophy Organization is a National 501 (c) tax-exempt organization. Relevant area(s) of interest: Myotonic Dystrophy

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to myotonic dystrophy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with myotonic dystrophy. 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 myotonic dystrophy. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “myotonic dystrophy” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit

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your search to “Organizations” and “myotonic dystrophy”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “myotonic dystrophy” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “myotonic dystrophy” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.24

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

24

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)25: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

25

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

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Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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MYOTONIC DYSTROPHY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Ablation: The removal of an organ by surgery. [NIH] Actin: Essential component of the cell skeleton. [NIH] Action Potentials: The electric response of a nerve or muscle to its stimulation. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] 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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [NIH] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU]

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Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Akinesia: 1. Absence or poverty of movements. 2. The temporary paralysis of a muscle by the injection of procaine. [EU] 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] 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 Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH)

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group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amyotrophy: A type of diabetic neuropathy that causes muscle weakness and wasting. [NIH] Anaerobic: 1. Lacking molecular oxygen. 2. Growing, living, or occurring in the absence of molecular oxygen; pertaining to an anaerobe. [EU] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] 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] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anomalies: Birth defects; abnormalities. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on

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the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Apamin: A highly neurotoxic polypeptide from the venom of the honey bee (Apis mellifera). It consists of 18 amino acids with two disulfide bridges and causes hyperexcitability resulting in convulsions and respiratory paralysis. [NIH] Apathy: Lack of feeling or emotion; indifference. [EU] Aqueous: Having to do with water. [NIH] Arcuate Nucleus: A nucleus located in the middle hypothalamus in the most ventral part of the third ventricle near the entrance of the infundibular recess. Its small cells are in close contact with the ependyma. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arteriolosclerosis: Sclerosis and thickening of the walls of the smaller arteries (arterioles). Hyaline arteriolosclerosis, in which there is homogeneous pink hyaline thickening of the arteriolar walls, is associated with benign nephrosclerosis. Hyperplastic arteriolosclerosis, in which there is a concentric thickening with progressive narrowing of the lumina may be associated with malignant hypertension, nephrosclerosis, and scleroderma. [EU] Arteriosclerosis: Thickening and loss of elasticity of arterial walls. Atherosclerosis is the most common form of arteriosclerosis and involves lipid deposition and thickening of the intimal cell layers within arteries. Additional forms of arteriosclerosis involve calcification of the media of muscular arteries (Monkeberg medial calcific sclerosis) and thickening of the walls of small arteries or arterioles due to cell proliferation or hyaline deposition (arteriolosclerosis). [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asymptomatic: Having no signs or symptoms of disease. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures.

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Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Natriuretic Factor: A potent natriuretic and vasodilatory peptide or mixture of different-sized low molecular weight peptides derived from a common precursor and secreted by the heart atria. All these peptides share a sequence of about 20 amino acids. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Azoospermia: Absence of spermatozoa in the semen, or failure of formation of spermatozoa. [EU]

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] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Basal cell carcinoma: A type of skin cancer that arises from the basal cells, small round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal cells: Small, round cells found in the lower part (or base) of the epidermis, the outer layer of the skin. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basal Ganglia Diseases: Diseases of the basal ganglia including the putamen; globus pallidus; claustrum; amygdala; and caudate nucleus. Dyskinesias (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include cerebrovascular disease; neurodegenerative diseases; and craniocerebral trauma. [NIH] Basal metabolic rate: Represents the minimum energy expenditure required for the maintenance of vital functions; normally the amount of energy expended, measured in calories, per unit of time at rest; measured after 14-18 hours of rest. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU]

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Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biopsy specimen: Tissue removed from the body and examined under a microscope to determine whether disease is present. [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] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Bulbar: Pertaining to a bulb; pertaining to or involving the medulla oblongata, as bulbar paralysis. [EU] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits

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and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] 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] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction. [NIH] Cataract: An opacity, partial or complete, of one or both eyes, on or in the lens or capsule, especially an opacity impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). [EU] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH]

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Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Polarity: Orientation of intracellular structures especially with respect to the apical and basolateral domains of the plasma membrane. Polarized cells must direct proteins from the Golgi apparatus to the appropriate domain since tight junctions prevent proteins from diffusing between the two domains. [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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] 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] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] 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] 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] Chemotherapy: Treatment with anticancer drugs. [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

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the passage of blood vessels and a nerve. [NIH] Cholecystectomy: Surgical removal of the gallbladder. [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] 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 Breakage: A type of chromosomal aberration which may result from spontaneous or induced breakage. Alkylating agents, various types of irradiation, and chemical mutagens have been found to cause induced chromosomal breakage. Breakage can induce base pair translocations, deletions, or chromatid breakage. [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] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [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 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] Clone: The term "clone" has acquired a new meaning. It is applied specifically to the bits of inserted foreign DNA in the hybrid molecules of the population. Each inserted segment originally resided in the DNA of a complex genome amid millions of other DNA segment. [NIH]

Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH]

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Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] 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] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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

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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] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [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] Constriction: The act of constricting. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] 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 discharge (e.g., in response to hypotension). [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with hypertrophy of the right ventricle. [EU] 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 Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or

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whether there is an associated hemorrhage. [NIH] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Cultured cells: Animal or human cells that are grown in the laboratory. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyst: A sac or capsule filled with fluid. [NIH] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] 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] Diagnostic procedure: A method used to identify a disease. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] 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] Diurnal: Occurring during the day. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] 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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity

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of another drug. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elasticity: Resistance and recovery from distortion of shape. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrocardiography: Recording of the moment-to-moment electromotive forces of the heart as projected onto various sites on the body's surface, delineated as a scalar function of time. [NIH]

Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [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] Energy balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH]

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Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Ependyma: A thin membrane that lines the ventricles of the brain and the central canal of the spinal cord. [NIH] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Essential Tremor: A rhythmic, involuntary, purposeless, oscillating movement resulting from the alternate contraction and relaxation of opposing groups of muscles. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

Extracellular: Outside a cell or cells. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU]

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Eye Movements: Voluntary or reflex-controlled movements of the eye. [NIH] Facial: Of or pertaining to the face. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Ferritin: An iron-containing protein complex that is formed by a combination of ferric iron with the protein apoferritin. [NIH] Fetal Movement: Motion of the fetus perceived by the mother and felt by palpation of the abdomen. [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] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Founder Effect: The principle that when a small subgroup of a larger population establishes itself as a separate and isolated entity, its gene pool carries only a fraction of the genetic diversity of the parental population. This may result in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as

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a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [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 Duplication: It encodes the major envelope protein and includes all the specifications for HBsAg. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels. [NIH] Gene Therapy: The introduction of new genes into cells for the purpose of treating disease by restoring or adding gene expression. Techniques include insertion of retroviral vectors, transfection, homologous recombination, and injection of new genes into the nuclei of single cell embryos. The entire gene therapy process may consist of multiple steps. The new genes may be introduced into proliferating cells in vivo (e.g., bone marrow) or in vitro (e.g., fibroblast cultures) and the modified cells transferred to the site where the gene expression is required. Gene therapy may be particularly useful for treating enzyme deficiency diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Code: The specifications for how information, stored in nucleic acid sequence (base sequence), is translated into protein sequence (amino acid sequence). The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (codon). [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic Markers: A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event. [NIH] Genetic Screening: Searching a population or individuals for persons possessing certain genotypes or karyotypes that: (1) are already associated with disease or predispose to disease; (2) may lead to disease in their descendants; or (3) produce other variations not known to be associated with disease. Genetic screening may be directed toward identifying phenotypic expression of genetic traits. It includes prenatal genetic screening. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] 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] 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]

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Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] 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] Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Guanine: One of the four DNA bases. [NIH] Haplotypes: The genetic constitution of individuals with respect to one member of a pair of allelic genes, or sets of genes that are closely linked and tend to be inherited together such as those of the major histocompatibility complex. [NIH] 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] Heartbeat: One complete contraction of the heart. [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]

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Hemoglobinuria: The presence of free hemoglobin in the urine. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] 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] Homeobox: Distinctive sequence of DNA bases. [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] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypogonadism: Condition resulting from or characterized by abnormally decreased functional activity of the gonads, with retardation of growth and sexual development. [NIH] Hypokinesia: Slow or diminished movement of body musculature. It may be associated

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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] Hypopituitarism: Diminution or cessation of secretion of one or more hormones from the anterior pituitary gland (including LH; FSH; somatotropin; and corticotropin). This may result from surgical or radiation ablation, non-secretory pituitary neoplasms, metastatic tumors, infarction, pituitary apoplexy, infiltrative or granulomatous processes, and other conditions. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hysterectomy: Excision of the uterus. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunofluorescence: A technique for identifying molecules present on the surfaces of cells or in tissues using a highly fluorescent substance coupled to a specific antibody. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH]

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Infantile: Pertaining to an infant or to infancy. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Ingestion: Taking into the body by mouth [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Insulin-like: Muscular growth factor. [NIH] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracellular Membranes: Membranes of subcellular structures. [NIH]

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Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] 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] Irradiation: The use of high-energy radiation from x-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 from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [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] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lacrimal: Pertaining to the tears. [EU] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid

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bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] 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] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lipid: Fat. [NIH] Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension. [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] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH]

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Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [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] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Major Histocompatibility Complex: The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) transplantation antigens, genes which control the structure of the immune responseassociated (Ia) antigens, the immune response (Ir) genes which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement. [NIH] Malabsorption: Impaired intestinal absorption of nutrients. [EU] 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]

Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Masseter Muscle: A masticatory muscle whose action is closing the jaws. [NIH] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Masticatory: 1. subserving or pertaining to mastication; affecting the muscles of mastication. 2. a remedy to be chewed but not swallowed. [EU] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH]

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Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Melanocytes: Epidermal dendritic pigment cells which control long-term morphological color changes by alteration in their number or in the amount of pigment they produce and store in the pigment containing organelles called melanosomes. Melanophores are larger cells which do not exist in mammals. [NIH] Melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fluidity: The motion of phospholipid molecules within the lipid bilayer, dependent on the classes of phospholipids present, their fatty acid composition and degree of unsaturation of the acyl chains, the cholesterol concentration, and temperature. [NIH] Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors. [NIH] 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 Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH]

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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] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monoclonal antibodies: Laboratory-produced substances that can locate and bind to cancer cells wherever they are in the body. Many monoclonal antibodies are used in cancer detection or therapy; each one recognizes a different protein on certain cancer cells. Monoclonal antibodies can be used alone, or they can be used to deliver drugs, toxins, or radioactive material directly to a tumor. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [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] Motility: The ability to move spontaneously. [EU] Motor Neurons: Neurons which activate muscle cells. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [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] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the

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function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Mycoplasma: A genus of gram-negative, facultatively anaerobic bacteria bounded by a plasma membrane only. Its organisms are parasites and pathogens, found on the mucous membranes of humans, animals, and birds. [NIH] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonia: Prolonged failure of muscle relaxation after contraction. This may occur after voluntary contractions, muscle percussion, or electrical stimulation of the muscle. Myotonia is a characteristic feature of myotonic disorders. [NIH] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Natriuretic Hormone: A low-molecular weight substance, possibly from the hypothalamus, which is released due to plasma volume expansion. It causes natriuresis in part by inhibiting sodium potassium ATPase. The development of hypertension may be the consequence of an abnormality in volume regulation induced by a defect in the renal response to the natriuretic effect of the natriuretic hormone. Do not confuse with atrial natriuretic factor or cardionatrin which is a different, well characterized hormone. [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] Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal period: The first 4 weeks after birth. [NIH] Neoplasia: Abnormal and uncontrolled cell growth. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized

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by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurosyphilis: A late form of syphilis that affects the brain and may lead to dementia and death. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] 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] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] 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] Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with nucleoproteins which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the

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information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Occupational Therapy: The field concerned with utilizing craft or work activities in the rehabilitation of patients. Occupational therapy can also refer to the activities themselves. [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] Opacity: Degree of density (area most dense taken for reading). [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Orbicularis: A thin layer of fibers that originates at the posterior lacrimal crest and passes outward and forward, dividing into two slips which surround the canaliculi. [NIH] Organ Culture: The growth in aseptic culture of plant organs such as roots or shoots, beginning with organ primordia or segments and maintaining the characteristics of the organ. [NIH] Organelles: Specific particles of membrane-bound organized living substances present in eukaryotic cells, such as the mitochondria; the golgi apparatus; endoplasmic reticulum; lysomomes; plastids; and vacuoles. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pacemaker: An object or substance that influences the rate at which a certain phenomenon occurs; often used alone to indicate the natural cardiac pacemaker or an artificial cardiac pacemaker. In biochemistry, a substance whose rate of reaction sets the pace for a series of interrelated reactions. [EU] Paediatric: Of or relating to the care and medical treatment of children; belonging to or

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concerned with paediatrics. [EU] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palpation: Application of fingers with light pressure to the surface of the body to determine consistence of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. [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] Paralysis: Loss of ability to move all or part of the body. [NIH] Paraparesis: Mild to moderate loss of bilateral lower extremity motor function, which may be a manifestation of spinal cord diseases; peripheral nervous system diseases; muscular diseases; intracranial hypertension; parasagittal brain lesions; and other conditions. [NIH] Paresis: A general term referring to a mild to moderate degree of muscular weakness, occasionally used as a synonym for paralysis (severe or complete loss of motor function). In the older literature, paresis often referred specifically to paretic neurosyphilis. "General paresis" and "general paralysis" may still carry that connotation. Bilateral lower extremity paresis is referred to as paraparesis. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologies: The study of abnormality, especially the study of diseases. [NIH] Pathologist: A doctor who identifies diseases by studying cells and tissues under a microscope. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

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] Perforation: 1. The act of boring or piercing through a part. 2. A hole made through a part or substance. [EU] Periodicity: The tendency of a phenomenon to recur at regular intervals; in biological systems, the recurrence of certain activities (including hormonal, cellular, neural) may be annual, seasonal, monthly, daily, or more frequently (ultradian). [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The

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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] Peritonitis: Inflammation of the peritoneum; a condition marked by exudations in the peritoneum of serum, fibrin, cells, and pus. It is attended by abdominal pain and tenderness, constipation, vomiting, and moderate fever. [EU] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phorbol: Class of chemicals that promotes the development of tumors. [NIH] Phorbol Esters: Tumor-promoting compounds obtained from croton oil (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C. [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] Phosphorylate: Attached to a phosphate group. [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 Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pigment: A substance that gives color to tissue. Pigments are responsible for the color of skin, eyes, and hair. [NIH] Pituitary Apoplexy: Sudden hemorrhage or ischemic necrosis involving the pituitary gland which may be associated with acute visual loss, severe headache, meningeal signs, cranial nerve palsies, panhypopituitarism, and rarely coma. The most common cause is hemorrhage (intracranial hemorrhages) related to a pituitary adenoma. Ischemia, meningitis, intracranial hypertension, and other disorders may be associated with this condition. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary Neoplasms: Neoplasms which arise from or metastasize to the pituitary gland.

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The majority of pituitary neoplasms are adenomas, which are divided into non-secreting and secreting forms. Hormone producing forms are further classified by the type of hormone they secrete. Pituitary adenomas may also be characterized by their staining properties (adenoma, basophil; adenoma, acidophil; and adenoma, chromophobe). Pituitary tumors may compress adjacent structures, including the hypothalamus, several cranial nerves, and the optic chiasm. Chiasmal compression may result in bitemporal hemianopsia. [NIH]

Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placentation: Development of a site of fetomaternal union for physiologic exchange, a placenta or placenta-like organ. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma Volume: Volume of plasma in the circulation. It is usually measured by indicator dilution techniques. [NIH] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

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] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for

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the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postnatal: Occurring after birth, with reference to the newborn. [EU] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [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] 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] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH]

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Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] 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] 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 Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. Quaternary protein structure describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). [NIH] Protein Isoforms: Different forms of a protein that may be produced from different genes, or from the same gene by alternative splicing. [NIH] Protein Kinase C: An enzyme that phosphorylates proteins on serine or threonine residues in the presence of physiological concentrations of calcium and membrane phospholipids. The additional presence of diacylglycerols markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by phorbol esters and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. EC 2.7.1.-. [NIH] Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein. EC 2.7.1.37. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] 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] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus

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of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [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] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

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] 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] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] 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] 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]

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Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombinant Proteins: Proteins prepared by recombinant DNA technology. [NIH] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red blood cells: RBCs. Cells that carry oxygen to all parts of the body. Also called erythrocytes. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Renal cell carcinoma: A type of kidney cancer. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Paralysis: Complete or severe weakness of the muscles of respiration. This condition may be associated with motor neuron diseases; peripheral nerve disorders; neuromuscular junction diseases; spinal cord diseases; injury to the phrenic nerve; and other disorders. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH]

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Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinal Ganglion Cells: Cells of the innermost nuclear layer of the retina, the ganglion cell layer, which project axons through the optic nerve to the brain. They are quite variable in size and in the shapes of their dendritic arbors, which are generally confined to the inner plexiform layer. [NIH] Retinoblastoma: An eye cancer that most often occurs in children younger than 5 years. It occurs in hereditary and nonhereditary (sporadic) forms. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Rhythmicity: Regular periodicity. [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] Salivary: The duct that convey saliva to the mouth. [NIH] Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of skeletal muscles that assist with muscle contraction and relaxation by releasing and storing calcium ions. [NIH] Satellite: Applied to a vein which closely accompanies an artery for some distance; in cytogenetics, a chromosomal agent separated by a secondary constriction from the main body of the chromosome. [NIH] 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] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a

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gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] 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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH]

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Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Sodium Channels: Cell membrane glycoproteins selective for sodium ions. Fast sodium current is associated with the action potential in neural membranes. [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] Somatotropin: A small peptide hormone released by the anterior pituitary under hypothalamic control. Somatotropin, or growth hormone, stimulates mitosis, cell growth, and, for some cell types, differentiation in many tissues of the body. It has profound effects on many aspects of gene expression and metabolism. [NIH] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Sound wave: An alteration of properties of an elastic medium, such as pressure, particle displacement, or density, that propagates through the medium, or a superposition of such alterations. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Speech pathologist: A specialist who evaluates and treats people with communication and swallowing problems. Also called a speech therapist. [NIH] Sperm: The fecundating fluid of the male. [NIH] Spermatozoa: Mature male germ cells that develop in the seminiferous tubules of the testes. Each consists of a head, a body, and a tail that provides propulsion. The head consists mainly of chromatin. [NIH]

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Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] 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] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] 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] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH]

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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] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic 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] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Testicle: The male gonad where, in adult life, spermatozoa develop; the testis. [NIH] Testicular: Pertaining to a testis. [EU] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] 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] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

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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] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Culture: Maintaining or growing of tissue, organ primordia, or the whole or part of an organ in vitro so as to preserve its architecture and/or function (Dorland, 28th ed). Tissue culture includes both organ culture and cell culture. [NIH] 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] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [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] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transgenes: Genes that are introduced into an organism using gene transfer techniques. [NIH]

Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH]

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Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Trinucleotide Repeats: Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes. [NIH] Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by troponin. [NIH] Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] 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] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] 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] Ubiquinone: A lipid-soluble benzoquinone which is involved in electron transport in mitochondrial preparations. The compound occurs in the majority of aerobic organisms, from bacteria to higher plants and animals. [NIH] Untranslated Regions: The parts of the messenger RNA sequence that do not code for product, i.e. the 5' untranslated regions and 3' untranslated regions. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinate: To release urine from the bladder to the outside. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi,

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protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] 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] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Vinca Alkaloids: A class of alkaloids from the genus of apocyanaceous woody herbs including periwinkles. They are some of the most useful antineoplastic agents. [NIH] Vincristine: An anticancer drug that belongs to the family of plant drugs called vinca alkaloids. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral vector: A type of virus used in cancer therapy. The virus is changed in the laboratory and cannot cause disease. Viral vectors produce tumor antigens (proteins found on a tumor cell) and can stimulate an antitumor immune response in the body. Viral vectors may also be used to carry genes that can change cancer cells back to normal cells. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH]

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Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Voltage-gated: It is opened by the altered charge distribution across the cell membrane. [NIH]

Volvulus: A twisting of the stomach or large intestine. May be caused by the stomach being in the wrong position, a foreign substance, or abnormal joining of one part of the stomach or intestine to another. Volvulus can lead to blockage, perforation, peritonitis, and poor blood flow. [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]

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INDEX 3 3-dimensional, 63, 121, 153 A Abdomen, 121, 134, 135, 140, 142, 149, 159, 163 Abdominal, 68, 121, 126, 149, 150 Aberrant, 5, 16, 23, 24, 25, 29, 42, 87, 121 Ablation, 121, 139 Actin, 16, 121, 145, 146, 162 Action Potentials, 86, 121 Acyl, 121, 144 Adaptability, 121, 128 Adaptation, 121, 151 Adenine, 121, 154 Adenosine, 88, 121, 150 Adenosine Triphosphate, 88, 121, 150 Adipocytes, 121, 142 Adolescence, 85, 121 Adrenal Cortex, 121, 131 Adrenergic, 31, 70, 74, 121, 134 Adverse Effect, 122, 157 Aerobic, 122, 162 Afferent, 122, 142 Affinity, 122, 158 Agar, 122, 151 Age of Onset, 122, 126, 162 Akinesia, 43, 122 Algorithms, 6, 122, 126 Alkaline, 122, 127 Alleles, 16, 18, 25, 84, 122, 142 Alpha Particles, 122, 154 Alternative medicine, 94, 122 Alternative Splicing, 16, 18, 22, 23, 26, 29, 47, 56, 122, 153 Alveoli, 122, 163 Amino Acid Sequence, 11, 123, 134, 136 Amplification, 25, 36, 123 Amyotrophy, 86, 123 Anaerobic, 123, 146 Anaesthesia, 28, 30, 41, 58, 74, 77, 123, 139 Anaesthetic, 30, 68, 123 Analogous, 88, 123, 161 Anatomical, 123, 125, 128, 139, 156 Anemia, 105, 123 Anesthesia, 28, 123, 141, 152 Animal model, 13, 15, 123 Annealing, 123, 151 Anomalies, 5, 32, 123

Antiarrhythmic, 38, 39, 123 Antibacterial, 123, 158 Antibiotic, 123, 158 Antibodies, 11, 13, 66, 87, 123, 125, 143, 145, 151 Antibody, 9, 12, 37, 84, 122, 123, 124, 130, 138, 139, 140, 141, 143, 145, 154, 158 Anticoagulant, 124, 153 Antigen, 52, 122, 123, 124, 130, 138, 139, 140, 143 Antioxidants, 44, 124, 142 Anus, 124, 130 Apamin, 7, 85, 124 Apathy, 39, 124 Aqueous, 124, 132, 142 Arcuate Nucleus, 37, 124 Arrhythmia, 123, 124 Arterial, 124, 131, 138, 153 Arteries, 60, 124, 126, 131, 144 Arterioles, 124, 126 Arteriolosclerosis, 124 Arteriosclerosis, 88, 124 Artery, 124, 126, 131, 156, 163 Articulation, 108, 124 Assay, 10, 12, 16, 24, 25, 124 Asymptomatic, 48, 124 Ataxia, 23, 25, 104, 105, 124, 138, 160 Atrial, 52, 125, 131, 146 Atrial Natriuretic Factor, 125, 146 Atrium, 125, 131, 163 Atrophy, 31, 33, 63, 85, 89, 104, 125, 147 Autoantibodies, 11, 125 Autoantigens, 125 Autonomic, 30, 34, 125, 147, 150 Axons, 125, 148, 156 Azoospermia, 52, 65, 125 B Bacteria, 12, 121, 123, 124, 125, 135, 137, 144, 146, 158, 161, 162 Bacteriophage, 125, 151, 161 Basal cell carcinoma, 68, 125 Basal cells, 125 Basal Ganglia, 125, 126, 139 Basal Ganglia Diseases, 125, 139 Basal metabolic rate, 31, 125 Biochemical, 5, 11, 15, 16, 20, 28, 29, 32, 37, 85, 122, 125, 142, 157 Biopsy, 8, 23, 126

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Biopsy specimen, 8, 126 Biosynthesis, 126, 157 Biotechnology, 26, 27, 94, 101, 103, 104, 105, 126 Bladder, 126, 139, 153, 162 Blood Coagulation, 126, 127, 160 Blood Platelets, 126, 157 Blood pressure, 32, 126, 138, 145, 158 Blood vessel, 126, 127, 129, 131, 133, 141, 158, 160, 161, 163 Blot, 84, 126 Body Fluids, 126, 158 Bone Marrow, 126, 136, 142, 145 Brain Neoplasms, 126, 138, 160 Breeding, 18, 126 Bulbar, 30, 126 C Caesarean section, 74, 77, 126 Calcification, 124, 126 Calcium, 74, 85, 126, 127, 130, 153, 156, 162 Carbohydrate, 127, 137, 152 Carbon Dioxide, 127, 135, 151, 155 Carcinogenic, 127, 140, 153, 159 Carcinogens, 127, 148 Carcinoma, 127 Cardiomyopathy, 20, 51, 127 Cardiovascular, 30, 34, 55, 66, 69, 127, 157 Case report, 50, 51, 60, 68, 78, 127, 129 Case series, 127, 129 Catabolism, 9, 11, 127 Catalytic Domain, 20, 88, 127 Cataract, 30, 45, 127 Caudal, 28, 127, 139, 152 Cell Cycle, 14, 26, 43, 88, 128 Cell Death, 25, 128, 146 Cell Differentiation, 11, 128 Cell Division, 104, 125, 128, 132, 140, 144, 151, 153, 157 Cell membrane, 86, 128, 135, 150, 158, 164 Cell Polarity, 26, 43, 128 Cell proliferation, 88, 124, 128 Cell Respiration, 128, 155 Central Nervous System, 11, 126, 128, 135, 137, 138, 148, 152, 157 Central Nervous System Infections, 128, 137, 138 Cerebellar, 125, 128, 155 Cerebral, 51, 125, 126, 128, 131, 134, 138 Cerebral Cortex, 125, 128 Cerebrospinal, 37, 128, 138 Cerebrospinal fluid, 37, 128, 138

Cerebrum, 128, 162 Character, 128, 132 Chemotherapy, 68, 128 Chin, 80, 128, 144 Cholecystectomy, 54, 129 Cholesterol, 129, 144, 159 Chromatin, 7, 24, 27, 39, 129, 158 Chromosomal, 5, 9, 13, 22, 123, 129, 138, 145, 156 Chromosome Breakage, 24, 129 Chromosome Fragility, 24, 129 Chronic, 104, 129, 133, 140, 141, 151, 154, 159 Chronic renal, 129, 151 Circadian, 58, 129 Circadian Rhythm, 58, 129 CIS, 3, 9, 15, 38, 129, 156 Clinical study, 35, 36, 78, 129 Clinical trial, 5, 19, 101, 129, 131, 132, 154 Clone, 13, 84, 129 Cloning, 13, 126, 129 Cofactor, 130, 153, 160 Collagen, 123, 130, 135 Colloidal, 130, 133 Colon, 104, 130, 141 Combinatorial, 18, 130 Complement, 130, 136, 141, 143 Complementary and alternative medicine, 77, 81, 130 Complementary medicine, 77, 130 Computational Biology, 101, 103, 130 Conduction, 17, 20, 54, 55, 64, 66, 85, 89, 131 Connective Tissue, 126, 130, 131, 132, 135 Constriction, 131, 141, 156 Contractility, 87, 131 Contraindications, ii, 131 Controlled study, 45, 131 Convulsions, 124, 131 Cor, 131, 139 Coronary, 32, 60, 131, 144 Coronary Thrombosis, 131, 144 Cortex, 131, 155 Cortical, 57, 131, 157, 160 Cortisol, 29, 58, 131 Cranial, 131, 137, 141, 148, 150, 151 Craniocerebral Trauma, 125, 131, 137, 138, 160 Crossing-over, 132, 155 Cultured cells, 10, 132 Curative, 132, 160 Cyst, 43, 132

167

Cytogenetics, 5, 30, 43, 132, 156 Cytoplasm, 14, 128, 132, 145, 147, 156, 160 Cytosine, 39, 132, 154 Cytoskeleton, 11, 87, 132 D Degenerative, 86, 132 Dehydroepiandrosterone, 86, 132 Deletion, 17, 18, 25, 132 Denaturation, 132, 151 Dendrites, 23, 132, 147 Dermis, 132, 155 Diagnostic procedure, 83, 94, 132 Diastole, 132 Diastolic, 54, 132, 138 Dilation, 51, 132, 138 Direct, iii, 3, 7, 10, 11, 16, 40, 128, 132, 155, 160 Distal, 7, 13, 86, 132 Diurnal, 67, 132 Dorsal, 132, 152 Double-blind, 36, 78, 132 Drug Interactions, 132 Dysplasia, 105, 133 Dystrophic, 19, 133 E Effector, 87, 130, 133 Effector cell, 133 Efficacy, 8, 133 Elasticity, 124, 133 Electrocardiogram, 64, 70, 133 Electrocardiography, 66, 133 Electrolyte, 133, 152, 158 Electrons, 133, 141, 143, 148, 154 Electrophoresis, 84, 133 Electrophysiological, 40, 79, 133 Elementary Particles, 133, 143, 147, 153 Embryo, 128, 133, 139 Endogenous, 125, 133, 153, 161 Endothelial cell, 9, 133, 160 End-stage renal, 129, 133, 151 Energy balance, 133, 142 Enhancer, 21, 133 Environmental Exposure, 134, 148 Environmental Health, 100, 102, 134 Enzymatic, 20, 26, 123, 127, 130, 134, 151, 156 Enzyme, 20, 88, 127, 133, 134, 136, 137, 151, 153, 159, 160, 164 Ependyma, 124, 134 Epidermis, 125, 132, 134 Epigastric, 134, 149 Epinephrine, 121, 134, 147, 162

Epithelial, 55, 134 Erythrocytes, 123, 126, 134, 155 Esophageal, 62, 134 Esophagus, 134, 159 Essential Tremor, 104, 134 Eukaryotic Cells, 12, 88, 134, 139, 148 Excitability, 38, 39, 134 Exocrine, 134, 149 Exogenous, 133, 134, 153, 162 Exon, 22, 122, 134 Expiration, 134, 155 Extensor, 134, 154 Extracellular, 88, 131, 134, 158 Extremity, 134, 149 Eye Movements, 38, 135 F Facial, 4, 17, 135 Faecal, 42, 62, 135 Family Planning, 101, 135 Fat, 121, 126, 131, 135, 142 Fatigue, 64, 135 Feces, 135, 159 Ferritin, 61, 135 Fetal Movement, 69, 135 Fetus, 135, 151, 152, 162 Fibrosis, 105, 135, 156 Fluorescence, 6, 43, 84, 135 Fold, 18, 135 Founder Effect, 35, 135 G Gallbladder, 121, 129, 135 Ganglia, 125, 135, 146, 150 Gap Junctions, 135 Gas, 127, 135, 138, 163 Gas exchange, 135, 163 Gastrin, 135, 138 Gastrointestinal, 45, 57, 134, 135, 157, 159 Gastrointestinal tract, 57, 135, 157 Gelatin, 135, 137, 160 Gene Duplication, 5, 136 Gene Expression, 7, 9, 10, 15, 17, 19, 21, 55, 105, 136, 158 Gene Silencing, 24, 136 Gene Therapy, 19, 48, 71, 136 Genetic Code, 136, 148 Genetic Counseling, 19, 136 Genetic Engineering, 126, 129, 136 Genetic Markers, 70, 136 Genetic Screening, 6, 136 Genetic testing, 89, 136, 152 Genotype, 13, 47, 66, 136, 150

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Myotonic Dystrophy

Gland, 121, 136, 149, 150, 153, 157, 159, 161 Glucose, 29, 32, 51, 85, 104, 136, 137, 140 Glucose tolerance, 32, 137 Glucose Tolerance Test, 32, 137 Glutathione Peroxidase, 137, 157 Glycine, 123, 137, 147, 157 Glycoproteins, 137, 141, 158 Gonad, 39, 137, 160 Governing Board, 137, 152 Grade, 19, 137 Gram-negative, 137, 146 Guanine, 39, 137, 154 H Haplotypes, 59, 70, 137 Headache, 137, 138, 150 Heartbeat, 137, 159 Hemoglobin, 123, 134, 137, 138 Hemoglobinopathies, 136, 137 Hemoglobinuria, 104, 138 Hemostasis, 138, 157 Hepatic, 137, 138 Hereditary, 3, 6, 12, 24, 46, 49, 86, 138, 146, 156 Heredity, 136, 138 Histones, 129, 138 Homeobox, 20, 21, 138 Homologous, 13, 122, 132, 136, 138, 157, 160 Hormonal, 8, 125, 138, 149 Hormone, 8, 24, 45, 129, 131, 134, 135, 138, 140, 142, 144, 146, 151, 156, 158, 160, 161 Hybrid, 7, 9, 129, 138 Hydrocephalus, 31, 50, 60, 138, 141 Hydrogen, 127, 132, 137, 138, 145, 147, 148, 154 Hydrolysis, 138, 152, 153 Hydroxyproline, 123, 130, 138 Hypertension, 124, 131, 138, 141, 146 Hypogonadism, 84, 138 Hypokinesia, 43, 138 Hypopituitarism, 55, 139 Hypoplasia, 85, 139 Hypothalamus, 124, 126, 139, 146, 150, 151 Hysterectomy, 68, 139 I Idiopathic, 52, 139 Immune response, 124, 125, 139, 143, 159, 163 Immune system, 133, 139, 143, 164 Immunodeficiency, 104, 139 Immunofluorescence, 23, 139

Immunoglobulin, 123, 139, 145 Immunologic, 11, 139 Immunology, 19, 122, 139 Impairment, 108, 124, 139, 144 In situ, 43, 84, 139 In Situ Hybridization, 43, 84, 139 In vitro, 10, 24, 136, 139, 151, 161 In vivo, 5, 11, 12, 15, 23, 24, 136, 139, 142 Incision, 126, 139, 141 Incompetence, 70, 139 Incontinence, 42, 62, 138, 139 Induction, 14, 16, 79, 139, 141 Infancy, 139, 140 Infantile, 84, 140 Infarction, 131, 138, 139, 140, 144 Infection, 47, 139, 140, 142, 143, 147, 159, 164 Inflammation, 88, 135, 140, 150, 151 Ingestion, 137, 140 Initiation, 140, 161 Insight, 15, 25, 140 Insulator, 24, 140 Insulin, 8, 29, 31, 35, 53, 62, 67, 71, 89, 137, 140, 162 Insulin-dependent diabetes mellitus, 140 Insulin-like, 8, 53, 140 Interleukin-1, 61, 140 Interleukin-2, 140 Interphase, 5, 140 Intestinal, 53, 137, 140, 143 Intestine, 140, 141, 164 Intoxication, 140, 164 Intracellular, 8, 26, 128, 140, 144, 152, 155, 156, 157 Intracellular Membranes, 140, 144 Intracranial Hemorrhages, 138, 141, 150, 160 Intracranial Hypertension, 137, 138, 141, 149, 150 Intrinsic, 15, 122, 141 Invasive, 54, 141, 143 Involuntary, 125, 134, 141, 146, 155 Ion Channels, 141 Ions, 133, 138, 141, 156, 158 Irradiation, 129, 141 Ischemia, 125, 141, 150 K Karyotype, 22, 141 Kb, 44, 100, 141 Ketamine, 28, 141 Kidney Disease, 100, 105, 141 Kinetics, 44, 141

169

L Lacrimal, 141, 148 Large Intestine, 140, 141, 155, 158, 164 Laryngeal, 28, 141 Larynx, 141, 161 Latent, 142, 152 Lectin, 142, 144 Lens, 46, 55, 127, 142 Leptin, 53, 55, 67, 142 Lesion, 142 Lethargy, 138, 142 Leukemia, 104, 136, 142 Life cycle, 12, 142 Ligament, 142, 153 Linkage, 7, 13, 20, 22, 44, 45, 46, 84, 136, 142 Linkage Disequilibrium, 7, 44, 45, 142 Lipid, 44, 124, 140, 142, 144, 162 Lipid Peroxides, 44, 142 Liver, 121, 135, 137, 138, 142 Lobe, 88, 142 Localization, 9, 13, 18, 20, 22, 26, 55, 142 Localized, 60, 87, 140, 142, 151 Loop, 12, 69, 142 Lymph, 133, 142 Lymphatic, 140, 142 Lymphocyte, 124, 143 Lymphoid, 123, 143 Lymphoma, 104, 143 M Macrophage, 140, 143 Magnetic Resonance Imaging, 34, 63, 67, 143 Magnetic Resonance Spectroscopy, 33, 143 Major Histocompatibility Complex, 137, 143 Malabsorption, 104, 143 Malignant, 25, 104, 124, 126, 143 Malnutrition, 125, 143, 145 Mandible, 4, 128, 143, 155 Manifest, 84, 143 Masseter Muscle, 4, 68, 143 Mastication, 143 Masticatory, 4, 67, 143 Maxillary, 4, 143 Medial, 124, 143, 148 Mediate, 12, 22, 143 Mediator, 140, 143, 157 MEDLINE, 101, 103, 105, 143 Medullary, 37, 56, 144 Meiosis, 144, 160

Melanin, 144, 150, 162 Melanocytes, 144 Melanoma, 104, 144 Membrane Fluidity, 79, 85, 144 Membrane Proteins, 85, 144 Meninges, 128, 131, 144 Mental, iv, 4, 24, 84, 85, 89, 100, 102, 106, 108, 128, 135, 139, 144, 154, 156 Mental Disorders, 139, 144, 154 Mental Retardation, 24, 84, 85, 89, 106, 108, 144 Metastatic, 126, 139, 144 MI, 50, 79, 119, 144 Microbe, 144, 161 Mitochondrial Swelling, 144, 146 Mitosis, 144, 158 Mitotic, 48, 144 Modeling, 6, 144 Modification, 123, 136, 144 Molecule, 11, 88, 124, 130, 133, 137, 138, 142, 145, 148, 151, 154, 163 Monitor, 145, 147 Monoclonal, 12, 55, 141, 145, 154 Monoclonal antibodies, 55, 145 Monocytes, 140, 145 Morphology, 4, 87, 127, 145 Mosaicism, 48, 68, 145 Motility, 62, 145, 157 Motor Neurons, 50, 145 Muscle Contraction, 145, 156 Muscle Fibers, 37, 145, 146, 162 Muscle Relaxation, 145, 146 Muscle Spindles, 69, 145 Muscular Atrophy, 23, 30, 86, 104, 145 Muscular Dystrophies, 9, 13, 19, 59, 133, 145 Musculature, 4, 138, 145 Mutagenesis, 12, 145 Mutagens, 129, 145 Mycoplasma, 12, 128, 146 Mydriatic, 132, 146 Myocardium, 19, 144, 146 Myopathy, 8, 11, 16, 20, 29, 35, 41, 54, 63, 65, 78, 87, 146 Myosin, 34, 145, 146, 162 Myotonia, 5, 7, 13, 18, 20, 21, 23, 55, 64, 78, 80, 84, 85, 86, 89, 146 N Natriuresis, 146 Natriuretic Hormone, 52, 146 NCI, 1, 99, 129, 146 Necrosis, 68, 140, 144, 146, 150, 157

170

Myotonic Dystrophy

Neonatal, 11, 28, 85, 146 Neonatal period, 28, 85, 146 Neoplasia, 104, 146 Neoplastic, 143, 146 Nephropathy, 141, 146 Nervous System, 23, 30, 104, 122, 128, 143, 146, 147, 149 Networks, 11, 146 Neural, 79, 122, 146, 149, 158 Neurodegenerative Diseases, 3, 24, 125, 146 Neurologic, 57, 108, 138, 147 Neuromuscular, 13, 15, 18, 19, 30, 33, 34, 37, 41, 51, 59, 64, 65, 67, 78, 85, 89, 108, 147, 155 Neuronal, 23, 38, 39, 147 Neurons, 23, 37, 56, 132, 135, 145, 147, 155, 160 Neuropathy, 6, 46, 123, 147 Neurosyphilis, 147, 149 Neurotoxic, 124, 147 Neurotransmitter, 121, 123, 137, 141, 147, 156, 159 Neutrons, 122, 141, 147, 154 Norepinephrine, 121, 147 Nuclear, 9, 21, 23, 26, 47, 48, 64, 89, 125, 133, 134, 146, 147, 156 Nuclear Envelope, 147 Nuclear Pore, 47, 147 Nuclear Proteins, 147 Nuclei, 6, 14, 43, 122, 133, 136, 138, 143, 144, 147, 148, 153 Nucleic acid, 87, 132, 136, 139, 146, 147, 154 Nucleus, 15, 21, 22, 23, 124, 125, 129, 132, 133, 134, 144, 145, 147, 148, 153, 159, 160 O Occupational Therapy, 92, 148 Oncogene, 104, 148 Opacity, 127, 148 Optic Chiasm, 139, 148, 151 Optic Nerve, 31, 148, 155, 156 Orbicularis, 4, 148 Organ Culture, 148, 161 Organelles, 132, 144, 145, 148 Orofacial, 4, 148 Ovary, 137, 148 Ovum, 142, 148, 164 Oxidation, 124, 137, 142, 148 Oxygen Consumption, 148, 155 P Pacemaker, 56, 148

Paediatric, 30, 58, 148 Palate, 4, 70, 149 Palliative, 149, 160 Palpation, 135, 149 Pancreas, 36, 121, 140, 149 Pancreatic, 104, 149 Pancreatic cancer, 104, 149 Paralysis, 122, 126, 149 Paraparesis, 149 Paresis, 28, 149 Paroxysmal, 104, 149 Particle, 149, 158, 161 Pathogenesis, 5, 8, 11, 13, 15, 16, 17, 18, 21, 22, 29, 35, 51, 58, 89, 149 Pathologic, 36, 71, 126, 131, 149, 154, 155 Pathologies, 14, 149 Pathologist, 149 Pathophysiology, 14, 15, 17, 20, 21, 23, 74, 149 Patient Education, 79, 108, 114, 116, 119, 149 Pelvic, 149, 153 Pelvis, 121, 149, 162 Peptide, 12, 123, 125, 142, 149, 152, 153, 158, 161 Perforation, 149, 164 Periodicity, 149, 156 Peripheral Nervous System, 147, 149, 159 Peritonitis, 150, 164 Pharmacologic, 123, 150, 161, 162 Phenotype, 6, 10, 13, 15, 18, 20, 21, 24, 25, 38, 47, 61, 66, 69, 85, 88, 89, 150 Phenylalanine, 150, 162 Phorbol, 150, 153 Phorbol Esters, 150, 153 Phospholipids, 135, 144, 150, 153 Phosphorus, 127, 150 Phosphorylate, 88, 150 Phosphorylated, 88, 150 Phosphorylation, 8, 26, 34, 85, 87, 88, 150 Physical Therapy, 77, 92, 150 Physiologic, 20, 126, 139, 150, 151, 154, 155 Physiology, 74, 121, 133, 150 Pigment, 144, 150 Pituitary Apoplexy, 139, 150 Pituitary Gland, 139, 150 Pituitary Neoplasms, 139, 150 Placenta, 151 Placentation, 52, 151 Plants, 126, 127, 136, 142, 145, 147, 151, 161, 162 Plaque, 4, 151

171

Plasma, 52, 123, 128, 136, 137, 138, 146, 151, 157 Plasma cells, 123, 151 Plasma Volume, 146, 151 Plasticity, 11, 151 Platinum, 142, 151 Pneumonia, 131, 151 Point Mutation, 25, 151 Polycystic, 105, 151 Polymerase, 84, 151 Polymerase Chain Reaction, 84, 151 Polymorphic, 27, 152 Polymorphism, 36, 84, 152 Polypeptide, 123, 124, 130, 152, 153, 164 Polysaccharide, 124, 152 Pons, 152, 155 Posterior, 4, 54, 89, 125, 132, 148, 149, 152 Postnatal, 152, 159 Postsynaptic, 152 Potassium, 85, 146, 152 Potentiates, 140, 152 Practice Guidelines, 102, 152 Precursor, 125, 133, 134, 147, 150, 152, 162 Predisposition, 25, 152 Prenatal, 29, 133, 136, 152 Presynaptic, 147, 152, 160 Prevalence, 4, 44, 48, 62, 84, 152 Probe, 26, 55, 84, 152 Procaine, 122, 152 Progression, 14, 17, 39, 123, 152 Progressive, 8, 16, 85, 124, 128, 129, 145, 146, 147, 153 Projection, 147, 148, 153, 155 Promoter, 16, 21, 24, 89, 153 Prone, 24, 153 Prophase, 153, 160 Propofol, 41, 153 Prostate, 25, 104, 153 Protease, 79, 153 Protein Binding, 16, 23, 153 Protein C, 7, 14, 123, 125, 135, 153, 162 Protein Conformation, 123, 153 Protein Isoforms, 122, 153 Protein Kinase C, 87, 153 Protein Kinases, 11, 20, 87, 88, 153 Protein S, 8, 26, 88, 105, 126, 136, 153, 156 Proteolytic, 20, 130, 153 Protons, 122, 138, 143, 153, 154 Psoriasis, 88, 154 Psychiatric, 40, 144, 154 Psychiatry, 40, 42, 50, 60, 62, 65, 154, 163 Psychic, 144, 154, 157

Psychoactive, 154, 164 Psychogenic, 154, 162 Public Policy, 101, 154 Publishing, 26, 154 Pupil, 132, 146, 154 Purines, 154, 157 Pyrimidines, 154, 157 R Race, 141, 154 Radiation, 68, 121, 133, 134, 135, 139, 141, 154, 164 Radiation therapy, 121, 141, 154 Radioactive, 138, 141, 145, 147, 154 Randomized, 133, 154 Receptor, 9, 11, 29, 31, 53, 67, 70, 85, 88, 121, 124, 153, 154, 157 Receptors, Serotonin, 155, 157 Recombinant, 8, 11, 13, 18, 87, 155, 163 Recombinant Proteins, 11, 13, 155 Recombination, 10, 12, 13, 27, 56, 136, 155 Rectum, 124, 130, 135, 139, 141, 153, 155 Recurrence, 129, 149, 155 Red blood cells, 85, 134, 155 Red Nucleus, 125, 155 Refer, 1, 130, 142, 147, 148, 155 Reflex, 66, 135, 145, 155 Refraction, 155, 158 Regimen, 133, 155 Renal cell carcinoma, 28, 155 Resorption, 138, 155 Respiration, 33, 77, 127, 145, 155 Respiratory Paralysis, 124, 155 Respiratory Physiology, 33, 155, 163 Reticular, 56, 155 Reticular Formation, 56, 155 Retina, 142, 148, 155, 156 Retinal, 148, 156 Retinal Ganglion Cells, 148, 156 Retinoblastoma, 104, 156 Retroviral vector, 136, 156 Rhythmicity, 67, 156 Ribose, 121, 156 Ribosome, 156, 161 S Salivary, 149, 156 Sarcoplasmic Reticulum, 51, 60, 79, 156 Satellite, 37, 156 Schizoid, 156, 164 Schizophrenia, 156, 164 Schizotypal Personality Disorder, 156, 164 Sclerosis, 104, 124, 156 Screening, 6, 30, 129, 136, 156

172

Myotonic Dystrophy

Second Messenger Systems, 156 Secretion, 35, 45, 53, 129, 139, 140, 156, 157 Secretory, 139, 157 Segregation, 155, 157 Seizures, 149, 157 Selenium, 45, 80, 157 Semen, 125, 153, 157 Sensibility, 123, 157 Sequence Homology, 87, 157 Sequencing, 152, 157 Sequester, 11, 18, 157, 160 Serine, 11, 15, 20, 87, 88, 89, 104, 153, 157 Serotonin, 56, 147, 155, 157, 162 Serum, 11, 51, 58, 130, 150, 157 Sex Characteristics, 121, 157, 160 Sex Determination, 105, 157 Side effect, 8, 122, 157, 161 Skeletal, 11, 14, 16, 20, 22, 23, 42, 53, 60, 61, 65, 70, 86, 87, 145, 156, 157, 162 Skeleton, 121, 157, 158 Small intestine, 138, 140, 158, 163 Smooth muscle, 85, 158, 159 Sodium, 85, 87, 146, 158 Sodium Channels, 87, 158 Soma, 158 Somatic, 25, 28, 121, 144, 150, 158 Somatotropin, 139, 158 Somnolence, 41, 57, 158 Sound wave, 131, 158 Specialist, 110, 132, 158 Species, 4, 134, 138, 141, 144, 145, 154, 157, 158, 159, 162, 163, 164 Specificity, 11, 60, 88, 122, 158 Spectrum, 7, 25, 158 Speech pathologist, 91, 158 Sperm, 48, 129, 158 Spermatozoa, 125, 157, 158, 160 Spinal cord, 128, 129, 134, 144, 146, 147, 149, 155, 159 Sporadic, 146, 156, 159 Statistically significant, 17, 159 Stem Cells, 13, 159 Steroid, 131, 159 Stimulus, 131, 133, 141, 155, 159, 160 Stomach, 121, 134, 135, 137, 138, 158, 159, 164 Stool, 130, 139, 141, 159 Strand, 10, 12, 16, 24, 27, 151, 159 Stress, 10, 27, 57, 131, 152, 159 Subacute, 140, 159 Subclinical, 67, 140, 157, 159 Subcutaneous, 8, 121, 159

Subspecies, 158, 159 Substance P, 157, 159 Substrate, 88, 127, 159 Sudden death, 64, 71, 159 Supplementation, 78, 159 Support group, 110, 159 Suppression, 7, 9, 21, 136, 159 Symphysis, 128, 153, 160 Symptomatic, 86, 160 Synapse, 121, 152, 160, 162 Synaptic, 11, 147, 160 Synaptic Vesicles, 160 Systemic, 126, 134, 140, 141, 154, 160 T Tachycardia, 54, 71, 160 Telangiectasia, 105, 160 Testicle, 137, 160 Testicular, 85, 89, 160 Testis, 160 Testosterone, 8, 67, 160 Thalamic, 125, 160 Thalamic Diseases, 125, 160 Therapeutics, 11, 12, 74, 78, 160 Thermal, 147, 151, 160 Threonine, 11, 15, 87, 88, 89, 104, 153, 157, 160 Threshold, 134, 138, 160 Thrombin, 153, 160 Thrombomodulin, 153, 160 Thrombosis, 153, 161 Thyroid, 49, 161, 162 Thyroid Gland, 161 Thyroid Hormones, 161, 162 Thyrotropin, 58, 161 Thyroxine, 150, 161 Tissue Culture, 23, 161 Tolerance, 121, 137, 161 Tonus, 4, 161 Toxic, iv, 15, 16, 18, 23, 133, 134, 142, 147, 157, 161 Toxicity, 16, 132, 161 Toxicology, 102, 161 Toxins, 124, 140, 145, 161 Trachea, 141, 161 Transcription Factors, 65, 161 Transduction, 20, 161 Transfection, 126, 136, 161 Transgenes, 11, 161 Translation, 14, 23, 123, 161 Translational, 19, 136, 162 Translocation, 31, 129, 162 Transmitter, 141, 143, 147, 160, 162

173

Transplantation, 51, 129, 143, 162 Trauma, 146, 162 Trinucleotide Repeats, 57, 162 Tropomyosin, 162 Troponin, 22, 162 Tryptophan, 130, 157, 162 Tuberous Sclerosis, 105, 162 Tumor suppressor gene, 25, 162 Type 2 diabetes, 35, 162 Tyrosine, 87, 88, 162 U Ubiquinone, 74, 162 Untranslated Regions, 18, 162 Urethra, 153, 162 Urinary, 68, 138, 139, 162 Urinary Retention, 68, 162 Urinate, 162 Urine, 126, 138, 139, 146, 162 Uterus, 68, 139, 162 V Vaccines, 162, 163 Vascular, 4, 9, 70, 132, 140, 151, 161, 163 Vector, 161, 163 Vein, 147, 156, 163 Venom, 124, 163 Venous, 153, 163 Ventilation, 35, 39, 79, 163 Ventral, 124, 139, 152, 163 Ventricle, 124, 131, 139, 163

Ventricular, 42, 51, 54, 60, 65, 71, 131, 138, 163 Ventricular Dysfunction, 60, 163 Veterinary Medicine, 74, 101, 163 Villi, 138, 163 Vinca Alkaloids, 163 Vincristine, 78, 163 Viral, 19, 71, 161, 163 Viral vector, 19, 71, 163 Virulence, 161, 163 Virus, 18, 125, 128, 133, 136, 151, 156, 161, 163 Viscera, 158, 163 Vitreous, 142, 155, 164 Vitro, 164 Vivo, 15, 24, 164 Voltage-gated, 87, 164 Volvulus, 45, 164 W White blood cell, 123, 143, 151, 164 Windpipe, 161, 164 Withdrawal, 14, 164 Womb, 162, 164 X Xenograft, 123, 164 X-ray, 5, 8, 135, 141, 147, 154, 164 Y Yeasts, 150, 164 Z Zygote, 145, 164 Zymogen, 153, 164

174

Myotonic Dystrophy

175

176

Myotonic Dystrophy