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

DUCHENNE MUSCULAR DYSTROPHY A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FE...

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DUCHENNE MUSCULAR 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., 1960Duchenne Muscular 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: 0-597-84397-X 1. Duchenne Muscular 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 Duchenne muscular 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 DUCHENNE MUSCULAR DYSTROPHY ...................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Duchenne Muscular Dystrophy ................................................... 4 E-Journals: PubMed Central ....................................................................................................... 26 The National Library of Medicine: PubMed ................................................................................ 29 CHAPTER 2. NUTRITION AND DUCHENNE MUSCULAR DYSTROPHY ............................................ 75 Overview...................................................................................................................................... 75 Finding Nutrition Studies on Duchenne Muscular Dystrophy.................................................. 75 Federal Resources on Nutrition ................................................................................................... 79 Additional Web Resources ........................................................................................................... 80 CHAPTER 3. ALTERNATIVE MEDICINE AND DUCHENNE MUSCULAR DYSTROPHY ...................... 81 Overview...................................................................................................................................... 81 National Center for Complementary and Alternative Medicine.................................................. 81 Additional Web Resources ........................................................................................................... 88 General References ....................................................................................................................... 89 CHAPTER 4. DISSERTATIONS ON DUCHENNE MUSCULAR DYSTROPHY ........................................ 91 Overview...................................................................................................................................... 91 Dissertations on Duchenne Muscular Dystrophy....................................................................... 91 Keeping Current .......................................................................................................................... 92 CHAPTER 5. CLINICAL TRIALS AND DUCHENNE MUSCULAR DYSTROPHY ................................... 93 Overview...................................................................................................................................... 93 Recent Trials on Duchenne Muscular Dystrophy....................................................................... 93 Keeping Current on Clinical Trials ............................................................................................. 96 CHAPTER 6. PATENTS ON DUCHENNE MUSCULAR DYSTROPHY ................................................... 99 Overview...................................................................................................................................... 99 Patents on Duchenne Muscular Dystrophy ................................................................................ 99 Patent Applications on Duchenne Muscular Dystrophy .......................................................... 102 Keeping Current ........................................................................................................................ 108 CHAPTER 7. BOOKS ON DUCHENNE MUSCULAR DYSTROPHY .................................................... 109 Overview.................................................................................................................................... 109 Book Summaries: Federal Agencies............................................................................................ 109 Book Summaries: Online Booksellers......................................................................................... 110 Chapters on Duchenne Muscular Dystrophy ............................................................................ 111 CHAPTER 8. PERIODICALS AND NEWS ON DUCHENNE MUSCULAR DYSTROPHY ....................... 113 Overview.................................................................................................................................... 113 News Services and Press Releases.............................................................................................. 113 Academic Periodicals covering Duchenne Muscular Dystrophy .............................................. 115 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 119 Overview.................................................................................................................................... 119 NIH Guidelines.......................................................................................................................... 119 NIH Databases........................................................................................................................... 121 Other Commercial Databases..................................................................................................... 123 APPENDIX B. PATIENT RESOURCES ............................................................................................... 125 Overview.................................................................................................................................... 125 Patient Guideline Sources.......................................................................................................... 125 Finding Associations.................................................................................................................. 130 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 133 Overview.................................................................................................................................... 133 Preparation................................................................................................................................. 133

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Finding a Local Medical Library................................................................................................ 133 Medical Libraries in the U.S. and Canada ................................................................................. 133 ONLINE GLOSSARIES................................................................................................................ 139 Online Dictionary Directories ................................................................................................... 141 DUCHENNE MUSCULAR DYSTROPHY DICTIONARY .................................................... 143 INDEX .............................................................................................................................................. 193

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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 Duchenne muscular 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 Duchenne muscular 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 Duchenne muscular 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 Duchenne muscular 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 Duchenne muscular 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 Duchenne muscular 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. DYSTROPHY

STUDIES

ON

DUCHENNE

MUSCULAR

Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Duchenne muscular 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 Duchenne muscular 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 “Duchenne muscular 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: •

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

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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 Duchenne Muscular Dystrophy The U.S. Government supports a variety of research studies relating to Duchenne muscular 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. 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 Duchenne muscular 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 Duchenne muscular dystrophy. The following is typical of the type of information found when searching the CRISP database for Duchenne muscular dystrophy: •

Project Title: ADENO-ASSOCIATED VIRUS (AAV) VECTORS TO IMPROVE MATURE MUSCLE FUNCTION Principal Investigator & Institution: Xiao, Xiao; Associate Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: Muscular dystrophies are a relatively common group of inherited degenerative muscle disease. Most types are caused by mutations in genes coding for membrance associated proteins in muscle. Duchenne muscular dystrophy (DMD) and limb-girdle muscular dystrophy (LGMD) often manifest themselves in young ages and lead to early morbidity with no currently available effective treatment. These diseases are recessive, loss-of- function of the corresponding gene product, which makes them

2 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).

Studies

5

suitable for gene replacement therapy. Recombinant adeno-associate virus (rAAV) is one promising gene replacement vector based on defective human parvoviruses. The rAAV system has attracted attention due to its non- pathogenicity, genomic integration, transduction of quiescent cells, and apparent lack of cellular immune reactions. In contrast to other viral vectors, rAAV is capable of efficiently bypassing the myofiber basal lamina and transducing mature muscle cells. We have demonstrated that rAAV vectors harboring a foreign gene can achieve highly efficient and sustained gene expression in mature muscle of immunocompetent animals for more than 1.5 years without detectable toxicity. Recently, significant improvement in vector production methodology has made it possible to generate high titer and high quality rAAV vectors completely free of helper adenovirus contamination. However, no experiments using rAAV vectors to restore the functional deficits in muscle tissue itself have been reported to date. Here, we propose to take advantage of rAAV vector system, to test two therapeutic genes (delta-sarcoglycan and a highly truncated dystrophin), under the control of two different promoter systems (viral/CMV or muscle- specific/MCK), in two relevant animal models of muscular dystrophies (Bio14.6 hamster for LGMD and mdx mouse for DMD). Two distinct vector delivery methods, local intramuscular infection versus systemic delivery will be utilized. We have the following three hypotheses to be tested. 1): muscle deficient in delta-sarcoglycan can be functionally rescued by genetic complementation using intramuscular AAV vector injection in the LGMD hamster model. 2) systemic delivery of the delta-sarcoglycan gene can be mediated by rAAV vectors through intra-artery or intra-ventricle injection. 3) a dystrophin mini-gene lacking the central rod domain will improve the function of dystrophin-deficient muscle when delivered into dystrophic mdx mice by AAV vectors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTISENSE OLIGONUCLEOTIDE SUPPRESSION OF DMD Principal Investigator & Institution: Wilton, Stephen D.; University of Western Australia Crawley, Wa, 6009 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): The ultimate goal of this project is to develop an antisense oligonucleotide (AO) therapy for Duchenne muscular dystrophy (DMD). Antisense oligonucleotides (AOs) can be used to reduce the severity of DMD by removing specific exons during pre-mRNA splicing, to either by-pass nonsense mutations or restore the reading frame around dystrophin genomic deletions. As a result of the treatment, dystrophin expression would be restored in dystrophic tissue and DMD patients would theoretically manifest only the milder phenotype of Becker Muscular Dystrophy (BMD). This project will explore the design and delivery of AOs to minimize the consequences of disease-causing dystrophin gene mutations. (1) Animal models of muscular dystrophy will be used to develop treatment regimens and assess therapeutic benefits in vivo. (2) AOs will be designed to target the most amenable splicing motifs at relevant exons in the human dystrophin gene transcript and will be evaluated in cultured human muscle cells. Although this approach cannot permanently correct the primary genetic lesion, we propose that repeated administration, preferably through systemic delivery, should be feasible. AO chemistries or modifications to increase stability and/or uptake, optimized for in vivo induction of exon skipping, will be developed and evaluated. Only periodic administration of AOs should be required to maintain therapeutic levels of induced dystrophin in dystrophic muscle. DMD is a serious disorder for which there is no effective treatment. AOs will not cure this devastating condition, however, AO-based splicing intervention has the potential to

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Duchenne Muscular Dystrophy

reduce the severity of DMD so that treated boys should be able to produce some functional dystrophin. This would be expected to moderate the severity of DMD and improve the quality of life for patients and their families. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DYSTROPHY

BIOENGINEERING

RESEARCH

PARTNERSHIP--MUSCULAR

Principal Investigator & Institution: Sweeney, Hugh Lee.; Professor and Chairman; Physiology; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-AUG-2005 Summary: (Applicant's abstract verbatim) The goal of this BRP is to utilize a number of aspects of bioengineering in order to develop tools and therapeutics for the treatment and monitoring of muscular dystrophies. The project is collaboration between three investigators and includes the following areas of bioengineering relevant to the PA: 1) cell and tissue engineering, 2) imaging and 3) therapeutics. Collectively we will delineate factors that when expressed in muscle may slow that rate of degeneration that is concomitant with either the complete (Duchenne muscular dystrophy) or partial (Becker muscular dystrophy) loss of dystrophin. These studies will utilize the mdx mouse as the animal model for dystrophin deficiency. The long-term goal is to gain the understanding and tools necessary to develop adeno-associated (AAV)-based gene therapy for Duchenne and Becker muscular dystrophies. Three parallel lines of investigation (each directed by one of the three investigators) are proposed: Section 1: a dissection the mechanical role of dystrophin and muscle adhesion proteins (directed by Dennis Discher); Section 2: an assessment of the functional benefits of restoring adhesion molecules to dystrophic muscle using recombinant adeno-associated virus gene delivery (directed by H. Lee Sweeney, Ph.D.); and Section 3: development of non-invasive methods for monitoring therapeutic benefits of dystrophin gene transfer (directed by Glenn Walter, Ph.D.). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CLINICAL AND MOLECULAR ANALYSIS OF OREGON EYE DISEASE Principal Investigator & Institution: Pillers, De-Ann M.; Associate Professor; Pediatrics; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2002; Project Start 30-SEP-1994; Project End 31-MAY-2004 Summary: (Verbatim from applicant's abstract): The title of the application is "Clinical and molecular analysis of Oregon Eye Disease." A more current title would be "Dystrophin and the retina." During the initial application period, it was shown that dystrophin, the product of the Duchenne muscular dystrophy (DMD) gene, is involved in retinal electrophysiology. Three lines of evidence support this. The position of a mutation in the DMD gene predicts the ERG phenotype, and abnormal ERGs were correlated in large part with mutations of a specific isoform of dystrophin, Dp260, which was identified and cloned from retina. New data suggests that other muscular dystrophies are associated with defects in retinal electrophysiology. Specifically, mouse models with defects in laminin-2 have abnormal ERGs. Dystrophin is part of a cellular continuum from the actin cytoskeleton to laminin and the extracellular matrix via a transmembrane group of proteins known as dystrophin-associated glycoproteins (DGC). It is hypothesized that defects in the interaction between retina-specific isoforms of dystrophin and the DGC result in altered retinal electrophysiology and an abnormal

Studies

7

ERG. It is proposed that the retinal isoform Dp260 plays an important role in retinal electrophysiology by interfacing with the DGC at the photoreceptor to bipolar synapse. It is further proposed that dystrophin isoforms with non-overlapping cellular distributions have distinct roles in retinal function. Three specific aims will be performed to test these hypotheses, involving: (1) defining genotype-phenotype correlations for the DGC performing ERGs on both mutant mice and patients with defects in these proteins; (2) defining the specific cell synapse responsible for the ERG abnormalities demonstrated in the mdxCV3 mouse by in vitro cell-specific electrophysiology; and (3) delineating the diversity of dystrophin isoform expression in retina and to determining unique aspects of isoform structure and expression that may contribute to retinal electrophysiology. The long-term goals are to delineate the pathway by which dystrophin contributes to the normal ERG. By so doing, proteins will be identified, which when mutated, will be candidate genes for inherited retinal disorders associated with abnormal electrophysiology. Dystrophin and other proteins including members of the DGC will be targets for future gene therapy approaches. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: COGNITIVE GENETIC ASPECTS OF DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Hinton, Veronica J.; Gertrude H Sergievsky Center; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-MAY-1996; Project End 30-JUN-2007 Summary: (provided by investigator): The objective of this study is to investigate neuropsychological function in individuals diagnosed with Duchenne muscular dystrophy (DMD) as a model for developmental neuroscience. DMD is a single-gene disorder that interferes with the expression of the protein dystrophin and its isoforms. The consequences of lack of dystrophin in muscle are well known; boys have progressive muscular weakness that results in death generally by their third decade of life. Dystrophin isoforms are also missing from the central nervous system, yet what functional consequences that may have is unclear. Interdisciplinary study of the cognitive profile, the behavioral attributes, and the molecular genetics of DMD will examine genotype/phenotype associations. The study will build on work that ascertained neuropsychological function in a group of 136 boys diagnosed with DMD and was completed during the tenure of an R29 award. Those data confirmed that boys with DMD who are of average intelligence have selective deficits in verbal working memory with intact declarative memory and visuospatial skills, poor social skills and delayed language developmental milestones. Selected subjects from the established cohort will be examined more thoroughly in focused paradigms to tease apart their language and short-term memory skills using a battery of tests designed to examine the hypothetical "phonological loop." Additionally, subjects will be tested on measures of social function and awareness. New subjects will also be enrolled to increase our sample size for genetic analyses. Subjects with more mild manifestations of the disorder (boys with Becker's muscular dystrophy and carrier females) will be tested on neuropsychological measures to determine whether they present with cognitive phenotypes. An ongoing longitudinal study of a sample of 26 boys will be continued with neuropsychological testing every other year. And newly characterized preschool boys with DMD will be followed to track their language and emotional development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Duchenne Muscular Dystrophy

Project Title: CORE--BIOLOGIC IMAGING Principal Investigator & Institution: Watkins, Simon C.; Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Description (provided by applicant): Visualization and localization of message, protein, or structural change resulting from gene expression is an essential step in evaluating the efficacy of successful gene transfer into cells and tissues. The goals of this program are to extend our understanding of the cellular pathology of Duchenne Muscular Dystrophy and to develop vector systems for dystrophin delivery using a variety of possible delivery systems, including AAV, Herpes, and stem cells. It is expected that these vectors will be used to use these vectors to generate clinically useful therapeutic regimens. In each case there is a fundamental need to define the level of incorporation of the delivered dystrophin into muscle, and to assess the effectiveness of the therapy. This identification varies from the low-resolution studies of whole tissues, defining correction of pathological phenotype, to high-resolution observations of successful subcellular passaging and presentation of protein. The Center for Biologic Imaging, in which this core service will be performed, is designed with this function in mind. It is equipped to perform a continuum of optical methods including all types of light and electron microscopy essential to this program project. Within the scope of this project at the light microscopic level these include: histological, immuno-histological and possibly live cell technologies. At the electron microscopic level we will provide fine structural and immuno-electron microscopic evaluation of specimens as a natural extension of the light microscopic analyses when needed. Furthermore, our considerable experience in computerized image processing and morphometry will allow quantitative analysis of observed phenomena to corroborate earlier, possibly quite subtle qualitative changes. This core will be used extensively by all projects, though the imaging tools used will vary from project to project. Preliminary data have shown the validity of these approaches, and we expect a very significant increase in the use of optical techniques within the formal setting of this program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: DUAL AAV VECTORS FOR DUCHENNE MUSCULAR DYSTROPHY THERAPY Principal Investigator & Institution: Duan, Dongsheng; Assistant Prof. of Microbio & Immunology; Molecular Microbiol and Immun; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 14-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD) is the most common form of inherited muscle disease. It usually leads to death from respiratory or cardiac failure by age 20. Currently, no effective treatment is available for this fatal disease. DMD is an X-linked genetic disease caused by dystrophin gene mutation. Gene therapy represents a very promising avenue to cure DMD. Recombinant adenoassociated virus (rAAV) mediates high-level persistent transgene expression in muscle. Recent clinical trials have further confirmed the efficiency and the safety of rAAV vectors in muscle. However, rAAVmediated DMD gene therapy has been significantly limited by the small viral packaging capacity. Only the highly truncated C-terminaldeleted versions of "micro-dystrophin" genes have been attempted. Both clinical and transgenic studies show that the C-terminal-inclusive larger genes (such as the 6.0-6.3kb "mini-dystrophin" genes and the approximately 4.7kb "C-terminal-inclusive micro-

Studies

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dystrophin" genes) are therapeutically superior. Unfortunately the strong therapeutic expression cassettes derived from these genes are too large to be packaged in a single AAV virion. We have recently developed several dual vector approaches to expand AAV packaging capacity. Among these, the concatamerization-based "trans-splicing" and "cis-activation" strategies hold great promise for delivering the C-terminal-inclusive larger dystrophin genes. However, the expression level achieved so far is not sufficient for DMD gene therapy. In this proposal, we plan to extend our previous findings and further explore the molecular mechanisms underlying these methods, in the hope of improving the transduction efficiency for DMD gene therapy. In particular, we will try to identify and overcome the rate-limiting barriers to transgene expression. These include problems associated with dual vector co-infection, concatamerization of AAV genome inside cell, and transcription, splicing, and stability of AAV concatamers. More important, we will apply this newly obtained information to generate the most effective trans-splicing and cis-activation AAV vectors for the C-terminal-inclusive larger dystrophin genes. Therapeutic potentials of these newly developed AAV vectors will be rigorously tested in the limb muscle, diaphragm, and heart of the murine DMD model (mdx mouse). A comprehensive array of assays will be used to examine the level of gene expression and the functional improvement in muscle histology and contraction. To address safety concerns, we also plan to evaluate the potential deleterious effects from putative truncated protein production in the trans-splicing method. Taken together, our findings will lead to the eventual application of these very promising dual AAV vector strategies to the human DMD gene therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ENHANCEMENT OF MYOBLAST CHEMOTACTIC MIGRATION Principal Investigator & Institution: Dominov, Janice A.; Boston Biomedical Research Institute 64 Grove St Watertown, Ma 02472 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Genetic defects underlying several degenerative muscle diseases such as Duchenne muscular dystrophy (DMD) are known, yet effective therapies for these disorders have not been found. One approach has been cell-based therapy in which normal myoblasts or genetically modified patient myoblasts are injected into diseased muscle with the intent that engraftment would be sufficient to compensate for protein deficiencies. Little success has been achieved with this approach however due to problems such as poor graft survival and impractical requirements for numerous muscle injections. Recently, systemic delivery of muscle precursor cells via tail vein or arterial injection in mice has been demonstrated resulting in low-level donor cell engraftment of regenerating muscle tissue. Vascular migration and extravasation of precursor cells thus occurs and could provide a useful route for improved cell-based therapy for these devastating diseases. The specific aims of the proposed work are to 1) Identify molecules expressed in myoblasts that are involved in the attachment to activated endothelial cells and promote trans-endothelial cell migration, 2) Improve the efficiency of myoblast trans-endothelial migration, if possible, by cytokine-induced expression of molecules known to regulate attachment and extravasation of immune system cells. Methods: Murine skeletal muscle myoblasts will be studied to determine expression levels of proteins known to function in leukocyte extravasation. Inflammatory cytokines will be used to induce myoblast expression of proteins relevant to chemotactic movement. In vitro trans-endothelial cell migration assays will be used to assess the role of specific chemokines, receptors and cell adhesion molecules in this process and the influence of inflammatory cytokine stimulation on myoblast migration.

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Normal myoblasts and those induced by cytokines will be injected into tail veins of mdx mice (model for DMD) undergoing muscle regeneration and extravasation into tissues assessed. Results will further our understanding of the mechanisms that promote systemic engraftment of donor myoblasts into diseased muscle could significantly advance the therapeutic use of myogenic precursor cells for the treatment of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE

EXCITATION-CONTRACTION COUPLING IN

DYSTROPHIC

Principal Investigator & Institution: Vergara, Julio L.; Professor; Physiology; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Abnormalities in the mechanisms of calcium regulation and excitation-contraction (EC) coupling that may be linked to the degeneration of skeletal muscle fibers in Becker Muscular Dystrophy (BMD) and in Duchenne Muscular Dystrophy (DMD) will be investigated using isolated muscle fibers from mdx mice. Cells from this animal model, like those of dystrophic patients, have deficiencies in the expression of the protein dystrophin. Although there is substantial biochemical evidence demonstrating the association of the dystrophinglycoprotein complex with transmembrane- and membrane-bound muscle proteins, little is known about its specific role in the physiological aspects of a muscle fiber. The main goal of this proposal is to obtain critical experimental evidence linking the absence of dystrophin with specific alterations in the electrical propagation in the transverse tubular system and calcium signaling machinery. Several possibilities that may explain these observations will be explored experimentally. Changes in intracellular calcium concentration triggered by electrical activity of the muscle fibers will be recorded with the aid of low affinity calcium sensitive fluorescent indicators and membrane potential changes in the transverse tubules will be monitored with potentiometric indicators. The investigations will be carried out using high-resolution optical methods that permit to assess the functional state of these critical steps of the EC coupling process, not only at the cellular level, but also within sub-regions of the muscle fiber and even within a single sarcomere. We will perform these measurements across three different age groups of the mdx mouse in order to understand the progression of the disease with time. We will also test if muscle fibers from a utrophin/dystrophin-lacking double mutant mouse, which exhibits a harsher pathology (similar to DMD), show signs of more pronounced defects in EC coupling. These types of experiments are necessary to unravel the mysterious role that dystrophin may play in the normal regulation of calcium metabolism in skeletal muscle. The knowledge gained in the proposed studies will help to elucidate the functional role of dystrophin in mammalian skeletal muscle, to this date the most fundamental and elusive problem in muscular dystrophy research. The enhanced methods proposed to detect defective steps in the EC coupling mechanisms within localized submicroscopic regions of mammalian muscle fibers may become the optimal choice for the future evaluation of genetic therapeutic procedures in sub-regions of a single muscle cell. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE AND CELL THERAPY OF DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Glorioso, Joseph C.; Professor and Chairman; Molecular Genetics & Biochem; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Muscular dystrophy is a common genetic disease that affects 1 in 3500 male births annually. The disease is characterized by early muscle hypertrophy followed by muscle degeneration and early death in adolescence resulting from failure of heart and diaphragm muscle. The disease results from mutations that affect expression or function of dystrophin, an important structural component of the subplasma membrane. Currently no treatment is available. The overall goal of the proposed research is to develop gene and cell therapeutic methods for treatment of muscular dystrophy. Clinical, pre-clinical and basic muscle cell development studies are described in which experts in gene transfer, muscle cell biology, animal models of muscular dystrophy and clinical applications are brought together in a manner to achieve the highest level of data sharing, synergy and creative solution finding will be possible. Project 1 (J Mendell) will define clinical end-points and identify cohorts of patient that would participate in a phase I dose escalation safety clinical trial using an AAV gene vector carrying the functional dystrophin minigene delivered to a single skeletal muscle and continue gene therapy clinical trials for limb girdle MD. In Project 2 (X Xiao and J Kornegay), will explore methods for improved AAV-dys gene delivery using the dog model. In Project 3 (J Huard), experiments using muscle stem cells will be carried out using dystrophic mouse models in attempts to achieve muscle delivery of normal muscle derived stem cells to engraft into diseased heart. In Project 4 (J Glorioso), a novel functional genomics approach to identify genes that participate in differentiation of mouse embryonic stem cells toward muscle cell lineages is proposed using HSV gene vector cDNA libraries obtained from muscle derived stem cells. The core programs are designed to directly support the projects in the form of Administration (Core A: J Glorioso and P Robbins), Clinical Vector Production (Core B: J Barranger), a muscular dystrophy dog colony (Core C: J Kornegey) and Imaging (Core D: S Watkins) to provide information on the results of gene transfer in animals and patients. Finally, our center includes a training program for residents interested in gene therapy for muscle disease. We believe this to be a timely and highly innovative proposal which is likely to provide new armroaches to the treatment of muscular dvstrophv. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: GENE THERAPY FOR DUCHENNE MUSCULAR DYSTROPHY Principal Investigator & Institution: Wolff, Jon A.; Professor; Pediatrics; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Copied from Applicant Abstract): Gene therapy promises to be a cure for the muscular dystrophies, such as Duchenne muscular dystrophy. Studies by my laboratory and others indicate that the transfer of the normal human dystrophin gene into dystrophic muscle (in the mouse model) prevents the death of the myofiber. The critical problem now is how to deliver the normal dystrophin gene to enough of the muscle cells and have it stably expressed in order to effect a cure. We have spectacular preliminary results that show that plasmid DNA can be delivered via a blood vessel into more than 10 percent of the muscle cells throughout the leg of a rat. This percentage of

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Duchenne Muscular Dystrophy

transfected muscle cells approaches the critical minimum percentage necessary to be curative in children with Duchenne muscular dystrophy. With this approach, multiple administrations should be possible, ensuring that a sufficient number of cells would be converted to dystrophin-positivity. Our studies also indicate that this approach should lead to stable expression of the gene. We have shown that the intravascular injection of naked plasmid DNA (pDNA) into the femoral artery of rats leads to very high foreign gene expression in skeletal muscle throughout the leg and without damaging the muscle. Previous experience with naked DNA and adenoviral vectors showed that the gene transfer efficiency decreased substantially when going from the young mouse, to adult mouse and then adult rat. The fact that we can achieve very efficient expression in an adult rat is quite encouraging. The objective of this proposal is to extend this approach to larger animals, non-human primates and the dog and its associated Duchenne model. If successful in primates and dogs, a human clinical trial in patients with Duchenne muscular dystrophy could begin in the near future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: GENTAMICIN TRIAL IN DUCHENNE AND LIMB GIRDLE DYSTROPHIES Principal Investigator & Institution: Mendell, Jerry R.; Neurology; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The study will determine if the aminoglycoside, gentamicin, has potential as a therapeutic medication for Duchenne muscular dystrophy (DMD). To fulfill this potential, long-term administration of gentamicin must be safe and improve muscle strength. Ideally, it will also increase dystrophin expression with binding at the muscle membrane. The testing paradigm will be a three-arm, sixmonth, double blind, randomized controlled trial of intravenous (IV) 7.5 mg/kg of gentamicin. Groups 1, 2, and 3 will each have 12 subjects. Group 1 will receive gentamicin every three days, while group 2 will receive drug every seven days. Group 3 subjects receive an IV placebo of 5% dextrose and saline; six subjects infused every three days and six others every seven days. In addition, gentamicin will be used in two shortterm, 14-day studies. If either of these groups responds to the 14-day administration by decreasing serum creative kinase (CK), then they become potential candidates for sixmonth administration. One group of 14-day subjects will have DMD with frameshift mutations. Despite commonly held dogma that aminoglycosides have no effect on this mutation-type, it is important to establish as effect by testing to see if CK drops. A positive outcome potentially reaches more patients, since this is the most common type of DMD gene mutation. Gentamicin will also be used to treat limb girdle muscular dystrophy subjects with stop codon mutations. If the serum CK is lowered, the potential for long-term treatment will be established for these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INTEGRIN REGULATION OF VASCULAR SMOOTH MUSCLE Principal Investigator & Institution: Burkin, Dean; University of Nevada Reno 204 Ross Hall Mailstop 325 Reno, Nv 89557 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 30-JUN-2008 Summary: This proposal seeks to understand the functional roles of the alpha7beta1 integrin in regulating vascular smooth muscle plasticity and in vascular disease. The alpha7beta1 integrin and the dystrophin glycoprotein complex connect muscle cells to

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their surrounding matrix. Duchenne Muscular Dystrophy (DMD) patients and mdx mice (a model for the human disease) have genetic mutations that result in an absence of dystrophin. DMD is characterized by progressive muscle weakness leading to early death from cardiopulmonary failure. DMD patients exhibit vascular abnormalities caused by weak smooth muscle cell attachment, poor contractile responses and excessive bleeding after surgery. In skeletal muscle of DMD patients and mdx mice, the alpha7beta1 integrin is increased and may partially compensate for the absence of the dystrophin complex. Enhanced transgenic expression of the alpha7beta1 integrin in skeletal muscle increases the longevity and decreases the pathology of severely dystrophic mice, supporting the hypothesis that alpha7beta1 and the dystrophin complex functionally overlap. Both dystrophin and the alpha7beta1 integrin are expressed in vascular smooth muscle where they mediate cell attachment to laminin. The dystrophin complex is involved in vascular smooth muscle plasticity and Ca 2+ homeostasis. This proposal will test the hypothesis that the alpha7beta1 integrin has a complementary role in regulating vascular smooth muscle cell plasticity. We will use mdx mice to determine if alpha7beta1 levels are increased in vascular smooth muscle in the absence of dystrophin. We will further determine if altered levels of the alpha7beta1 integrin result in alterations of Ca 2+ homeostasis, cell contractility, vascular tone, and cell differentiation. Molecules downstream of the integrin will be analyzed to determine the mechanisms by which increased alpha7beta1 compensates for the absence of dystrophin. The alpha7beta1 integrin may play a critical role in vascular plasticity and disease and these studies may shed light on the underlying molecular basis of vascular function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ION CHANNELS AND CHEMICALS CONTROLLING SYNAPSE STABILITY Principal Investigator & Institution: Mcardle, Joseph J.; Professor; Pharmacology and Physiology; Univ of Med/Dent Nj Newark Newark, Nj 07103 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2007 Summary: (provided by applicant): Synapses are the major locus of information transfer within our brain as well as the target of numerous pathologies which can afflict humans from development in utero to death. Therefore, major research effort is given to understanding synapse formation and stabilization throughout life. The scientific literature concerning synapses is rich with discovery of fundamental principles derived from study of the neuromuscular junction (NMJ). In particular, proteins responsible for NMJ function, formation, and stability are relatively well understood. Nevertheless, fundamental questions remain concerning interactions between these proteins. An important experimental model suggests that heterogeneous activity of AChRs influences stability of the adult NMJ. This proposal modifies and extends that model to the developing NMJ where co-expression of immature gamma and mature epsilon AChRs during the critical phase of NMJ maturation produces heterogeneity of end-plate activity. Our model suggests that end-plate areas rich in epsilon AChR mediate Ca 2+ influx which activates co-localized nitric oxide synthase (nNOS). The nitric oxide (NO) produced diffuses to nerve terminals competing for the motor end-plate. New preliminary data suggest that NO enhances Ca2+ currents and transmitter release at adult motor nerve terminals. Thus, developing nerve terminals activating end-plate loci containing the epsilon AChR may be functionally enhanced and nurtured via NO activation of presynaptic guanylyl cyclase. In contrast, NO may repress function and stability of competing nerve terminals activating epsilon AChR poor end-plate foci. The

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mouse Triangularis sterni (TS) preparation facilitates exact testing of our model. Our preliminary data show that the TS preparation isolated from neonatal mice allows simultaneous recording of nerve terminal currents and post-synaptic events at endplates receiving innervation from terminals originating in distinct nerve trunks. This allows unprecedented study of the function of, and NO-mediated cross talk between, mammalian nerve terminals competing for a postsynaptic target. The availability of epsilon subunit and nNOS knock out mice, as well as the epsilon AChR selective ligand Waglerin- 1 further strengthen experiments proposed to test our model. Additional novel preliminary data suggest that insulin, an activator of the neuronal K-ATP channel, suppresses quantal release of Ach at the adult NMJ. Therefore, a second goal of this proposal is to discover if insulin, as well as glucose, effects the function, and eventual stability, of nerve terminals competing at the developing NMJ. This will be explored in a non-obese mouse model of type I diabetes. Overall, this research is clinically relevant since NO signaling cascades are significantly altered in Duchenne muscular dystrophy as well as animal models of stroke. In addition, altered function of the epsilon AChR is responsible for NMJ pathology associated with slow channel congenital myasthenic syndrome. The proposed evaluation of insulin effects is novel and will enhance understanding of the neurologic consequence of adult and juvenile forms of diabetes. The knowledge gained from this research will enlighten future molecular approaches to treating pathologies which afflict children and adults. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MODIFIED ADENOVIRAL VECTORS FOR GENE TRANSFER TO MUSCLE Principal Investigator & Institution: Chamberlain, Jeffrey S.; Professor; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: The long range goal of this project is to develop viral vectors of gene therapy of muscle diseases. In transgenic mdx mice, a model for Duchenne muscular dystrophy (DMD), low-level expression of dystrophin mini-genes prevents dystrophy through at least years of age. Modified adenoviral vectors are being developed to test whether gene transfer can treat, rather than prevent, dystrophy in young and aging animals. Adenoviruses (Ad) efficiently infect muscle but they display a number of disadvantages preventing use in clinical trials for DMD. Ad vectors trigger a host immune response that prevents long term gene expression in vivo. Ad vectors have a cloning capacity of only approximately 8 kb, smaller than the 14 kb dystrophin cDNA. Finally. strong viral promoters typically used to driven transgene expression from Ad vectors are often shutoff in vivo. A new Ad vector is being developed that could overcome each of these problems. Our hypothesis is that Ad vector systems lacking all viral genes can support long-term gene expression. in muscle. Critical to this 'gutted' vector strategy is the development of a self-limiting helper virus system. Vector lacking viral genes can only be propagated in the presence of a helper virus that produces proteins needed for Ad replication and packaging. However, it the preparations of gutted vector contain significant levels of the helper virus, then the contaminating helper virus will trigger the same immune response that the gutted system is designed to avoid. Our strategy for perfecting the gutted vector system relies heavily on improvements to the helper viruses used for gutted vector propagation. The Cre-LoxP system will be used to disable packaging of helper DNA into virions. Modified Ad packaging cell lines will also be used to grow helper viruses lacking a subset of genes required for propagation and gene expression in vivo. Muscle specific promoters are also being developed to limit virally-

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delivered transgene expression to muscle tissues. Finally, a functional homologue of dystrophin [utrophin] will be tested for the ability to prevent an immune response against dystrophin. This gutted vector/helper virus system will be tested in vivo to identify any residual host immune responses that might be generated, and if needed a variety of vector modifications will be tested to attenuate this response. If successful, these studies could lead to a treatment for DMD and other muscle diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MOLECULAR DYSTROPHINOPATHIES

IDENTIFICATION

OF

CANINE

Principal Investigator & Institution: Smith, Bruce F.; Associate Professor; Scott-Ritchey Research Center; Auburn University at Auburn Auburn University, Al 36849 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Duchenne muscular dystrophy is a common inherited disease, affecting approximately 1 in 3000 live male births. Currently, there is no effective therapy for this disease, however, new therapies are being proposed that offer hope to patients and their families. These therapies must be evaluated for their efficacy in the most stringent manner possible, and in the case of DMD, that requires an appropriate animal model. The long term GOAL of this project is to characterize the molecular defects present in 3 new canine models of dystrophin deficiency. It is hypothesized that these models accurately reflect the depth and breadth of mutations and their effects that is seen in the human population. Current murine models require that multiple genes be knocked out to show the same disease that the loss of dystrophin causes in boys. The canine model system is the only model which appropriately reflects the relentlessly progressive and ultimately fatal disease of boys. However, the complexity of the dystrophin gene and thus the variety of mutations possible, require the availability of multiple models in which to test therapies. The best source of these models continues to be spontaneously occurring canine disease. This severely handicaps the utility of these models in evaluating new therapies. This project will not only elucidate the mutation in these three new canine models, but it will also create a set of tools that will allow investigators worldwide to rapidly evaluate further spontaneous cases of canine muscular dystrophy for their usefulness, both in exploring new therapies and in gaining new insight into the mechanism behind Duchenne muscular dystrophy. Specifically, we propose to use panels of monoclonal antibodies with known specificity to dystrophin, simultaneously with PCR amplification of the coding sequence to rapidly scan for mutations. Suspicious areas will be sequenced to determine if the mutation is contained within. Once the mutations are identified, their effect on transcription, translation and the presence of dystrophin will be evaluated and compared to similar human mutations to determine if there is a pathophysiological correlation between species and their mutations. Successful completion of this project will result in the addition of three models of human dystrophin deficiency to the tools available to investigators seeking novel treatments. The correlation of these mutations with the clinical course of the disease will allow therapies to be evaluated under a variety of clinical circumstances. These mutations will provide new and different genetic backgrounds upon which various therapies, and in particular genetic therapies, may be examined in a large, outbred animal species. 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: MUSCLE RESPONSE TO STRESS IN CANINE MUSCULAR DYSTROPHY Principal Investigator & Institution: Childers, Martin K.; Associate Professor; Phys Med and Rehabilitation; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2002; Project Start 01-MAR-1999; Project End 28-FEB-2004 Summary: This project will provide the applicant with the research skills required to develop and assess rehabilitation treatments that enhance function for patients with muscular dystrophy. Throughout a doctoral program in physiology, a major portion of effort will be devoted to a mentored research project which will examine the relationship between mechanical stress and muscle fiber injury in a canine homolog of

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Duchenne muscular dystrophy. The central hypothesis of this research is that fiber damage in dystrophin-deficient muscle results, in part, from an exaggerated response to mechanical stress incurred during contraction. Furthermore, muscles involved in lengthening contractions are subject to greater stress than other muscles, and are preferentially injured. The central hypothesis will be tested in selected hindlimb muscles of dystrophic dogs by evaluating cellular and physiological features of muscle fiber response to varying levels of imposed stress. Although the mdx mouse is more readily available and a more commonly used experimental model, the dystrophic dog expresses clinical features analogous to humans with Duchenne muscular dystrophy. Aim 1 will correlate muscle membrane damage with myofiber necrosis: Aim 2 will compare regenerative features in muscles involved in lengthening contractions with muscles involved in shortening contractions: Aim 3 will determine if a lower threshold to stressinduced injury exists in dystrophic fibers compared to controls: and Aim 4 will determine if reducing mechanical stress during growth will eliminate or decrease the exaggerated fiber necrosis and remodeling seen in the adult gastrocnemius muscle. It is anticipated that findings will improve the understanding of how dystrophic muscle responds to physical stress resulting in improved treatment for patients with Duchenne muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MUSCLE CARDIOMYOPATHY

STEM

CELL-BASED

THERAPIES

FOR

Principal Investigator & Institution: Huard, Johnny; Henry J. Mankin Associate Professor of o; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2008 Summary: Cardiomyopathy is a serious heart disease that often leads to congestive heart failure, a condition in which the heart muscle can no longer effectively pump blood. Patients that suffer from various muscle diseases, including Duchenne muscular dystrophy (DMD), develop progressive cardiomyopathy. Cellular cardiomyoplasty (CCM), a procedure that involves the transplantation of exogenous cells into damaged myocardium, has been proposed as a possible therapy to regenerate diseased myocardium and deliver therapeutic genes. Although a wide variety of cell types has been used for CCM, various limitations (including ethical, biological, or technical challenges) have impeded their suitability for use in human patients. We recently have used the modified preplate technique to isolate a novel population of muscle-derived stem cells (MDSCs) that display improved transplantation capacity in skeletal muscle when compared to satellite cells. The MDSCs' ability to proliferate in vivo for an extended period of time-- combined with their strong capacity for serf-renewal, multipotent differentiation, and immune-privileged behavior--reveals, at least in part, a basis for the benefits associated with their use in cell transplantation in skeletal muscle. The proposed project will investigate the use of MDSCs as a novel cell source for cardiac cell transplantation in a cardiomyopathic murine model of muscular dystrophy. We already have observed that MDSCs delivered by intra-cardiac injection display good cell survival and can deliver dystrophin within the dystrophic myocardium. In this project we will investigate whether MDSCs implanted in the hearts of dystrophic mdx mice display an improved transplantation capacity when compared to conventional satellite cell implantation (Aim #1). We then will explore the relative contribution of the MDSCs' capacity for long-term proliferation and self-renewal (Aim #2) to the increased regenerative capacity of these cells after transplantation in heart muscle. Finally, we will

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determine the degree to which development of approaches to prevent fibrosis (Aim #3) and improve angiogenesis (Aim #4) would further enhance the regenerative capacity of muscle-derived cells in the heart. This project will increase our understanding of the basic biology of myogenic cell populations that display stem cell characteristics. This information may, in turn, unveil new techniques to improve heart regeneration and repair via the transplantation of muscle-derived stem cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: MYELOID CELL FUNCTION IN MUSCULAR DYSTROPHY Principal Investigator & Institution: Tidball, James G.; Professor; Physiological Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 24-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Duchenne muscular dystrophy (DMD) is the most common, inherited, lethal disease of childhood. Although mutations in the dystrophin gene are primarily responsible for DMD and animal models of DMD, many features of dystrophinopathies indicate that secondary processes can contribute substantially to pathology. Recent findings have indicated that the immune system can contribute significantly to the pathological progression of dystrophin-deficiency in the mdx mouse model of the disease. The long-term goal of our studies of the pathology of dystrophindeficiency is to identify the specific immune cells and mechanisms that promote the pathology of dystrophin-deficiencies, after which we will use that information for the development of immune-based therapeutics. Although our preliminary data implicate both myeloid and lymphoid cells in promoting the dystrophic pathology, the studies proposed here will focus on cytotoxic mechanisms that are mediated by macrophages and eosinophils in dystrophic muscle. Our rationale for focusing on these specific myeloid cells is that our preliminary findings strongly implicate these cells in promoting the pathology of dystrophin-deficiency through both innate and acquired immune responses. Our general strategy will be to assess the effect on muscle pathology of depletion of specific myeloid cell populations from the dystrophic mdx mouse. In addition, the effect of those depletions on the lifespan of the dystrophic mdx/utrophindeficient mice will be assessed because these mice die from muscular dystrophy at an early age. We will also test whether introducing null mutations of the inducible nitric oxide synthase gene or major basic protein gene into mdx mice will reduce muscle pathology, because our findings implicate cytotoxic pathways in the mdx pathology that involve the products of these genes. Results of the study proposed here will permit us to determine whether therapeutic approaches that are based on reducing myeloid cell mediated pathology can be productive approaches to the treatment of these forms of muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MYOSIN GENE DIVERSITY AND FUNCTION Principal Investigator & Institution: Leinwand, Leslie A.; Professor and Chair; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2003; Project Start 01-SEP-1981; Project End 31-JAN-2007 Summary: (provided by applicant): The formation of skeletal muscle and its adaptation to the environment requires precise temporal and spatial regulation of a host of proteins, including the molecular motor protein, myosin. The precise adaptation of myosin heavy chain (MyHC) genes requires coordinate regulation, yet, little is known

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about its molecular biology. We propose to define the molecular aspects of fiber type specificity and the pathways that regulate these genes. In mammals, there are 6 characterized skeletal muscle MyHC genes. Although muscle fibers expressing each of them have unique contractile velocities, the enzymatic properties of the individual motors remain elusive. We will express the 6 human skeletal MyHC head domains in an inducible mammalian system and characterize their biochemical and biophysical properties. Despite the perception that the sarcomeric MyHC gene family had been defined, examination of the human genome revealed a novel striated MyHC that we propose to characterize. We have found that it is expressed in cardiac and skeletal muscle and that phylogenetically, it appears most closely related to the alpha and beta MyHC genes. We will compare the sequence features of the coding, regulatory regions and the intron/exon organization of this gene in mouse and human. We will also determine its expression in development and in the adult and test whether wellcharacterized muscle adaptations alter its pattern of expression. Until recently, there had been no diseases associated with mutations in skeletal MyHC. However, a mutation in the MyHC IIa gene has been reported which we propose to model in transgenic mice. We are also characterizing the IId gene of a childhood myopathy patient who appears to be null for its expression. An interesting feature of the MyHC gene family that may have relevance to Duchenne muscular dystrophy (DMD) is that the most abundant MyHC protein in rodents, IIb, is barely detectable in normal adults. However, we find its expression is induced in DMD. Because of the potential functional consequences of expression of this fast myosin motor, we will define the molecular basis for this species difference and its induction. Finally, we will extend our studies of an unusual cell type, the myofibroblast, which has properties of both muscle and nonmuscle cells, including expression of adult fast skeletal MyHCs, to understand the pathways that define these cells and distinguish them from skeletal muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PATHOGENESIS OF EMERY-DREIFUSS MUSCULAR DYSTROPHY Principal Investigator & Institution: Worman, Howard J.; Associate Professor; Medicine; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 15-MAY-2003; Project End 30-APR-2008 Summary: (provided by applicant): Emery-Dreifuss muscular dystrophy (EDMD) is characterized by region muscle contractures, slow progressive muscle wasting and cardiomyopathy with atrioventricular conduction block. Indistinguishable forms of EDMD are inherited in autosomal dominant and X-linked manners. Mutations in emerin, an integral protein of the nuclear envelope inner membrane, cause X-linked EDMD. Autosomal dominant EDMD is caused by mutations in the LMNA gene, which encodes the nuclear envelope intermediate filament proteins lamins A and C. It is not known how mutations in nuclear envelope proteins cause muscular dystrophy. We hypothesize that mutations in these chromatin-associated proteins cause changes in the expression of genes responsible for muscle cell differentiation or survival. Our goal is to test this hypothesis using a combination of studies in transfected cells, patients' cells and tissues and animals models. In the first specific aim, we will use fluorescence microscopy and photobleaching methods to investigate how lamin A and C mutants from patients with autosomal dominant EDMD influence the mobility of emerin in the inner nuclear membrane. We will determine if mutant lamins A and C cause emerin to "escape" from the inner nuclear membrane into the continuous endoplasmic reticulum. As patients with X-linked EDMD do not have emerin in the inner nuclear membrane, this finding would demonstrate a connection between the X-linked and autosomal

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dominant forms of the disease. In the second aim, we will use microarrays to compare gene expression in cells from patients with autosomal dominant EDMD to X-linked EDMD and Dunnigan-type partial lipodystrophy, a disease caused by mutations in different regions of lamins A and C. This will establish if emerin and lamin mutations responsible for EDMD alter expression of the same genes. We will also use microarrays to determine gene expression profiles in muscles from lamin A/C "knockout" mice that develop muscular dystrophy and compare the results to what is known about pathologic alterations in gene expression in Duchenne muscular dystrophy. The results will be confirmed in tissues from human subjects with EDMD. In Aim 3, we will generate transgenic mice expressing human lamin A mutants and determine if they develop pathological abnormalities of EDMD and similar gene expression changes. This work will help establish how abnormalities in the nuclear envelope cause muscular dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: REGULATION OF SKELETAL MUSCLE REGENERATION Principal Investigator & Institution: Li, Yi-Ping; Medicine; Baylor College of Medicine 1 Baylor Plaza Houston, Tx 77030 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Tumor necrosis factor-alpha (TNF-alpha) is traditionally recognized as a circulating mediator that stimulates muscle catabolism in inflammatory diseases. However, recent discoveries indicate that TNF-alpha plays a more complex and more fundamental role in skeletal muscle. It is now clear that skeletal myocytes constitutively express TNF-alpha. Biological processes that demand myofiber regeneration - degenerative muscle diseases (inflammatory myopathies and Duchenne muscular dystrophy), injury and exercise -- accelerate TNF-alpha expression by myocytes. Further, it is increasingly evident that TNF-alpha is critical for muscle regeneration because it accelerates myogenic gene expression. Based on growing evidence from our and other laboratories, we propose that TNF-alpha functions as an autocrine/paracrine modulator of muscle regeneration by promoting the expression of adult-type muscle proteins during early differentiation via activating MADS-box myogenic factors, MEF2 and SRF, and a muscle hypertrophy mediator GATA-2. Three specific aims will be pursued to test this model. Aim 1. To evaluate upregulation of TNF-alpha as an autocrine modulator of primary myoblast differentiation. TNF-alpha expression during differentiation induced by distinct stimuli (serum restriction, cell confluence and cyclic stretch), and effects of TNF-alpha on adult-type muscle protein expression during differentiation will be determined in rat and mouse primary myoblasts. Aim 2. To determine whether TNF-alpha promotes muscle regeneration in vivo. Effects of TNF-alpha deficiency on muscle regeneration evoked by cardiotoxininduced muscle injury will be evaluated in mice with genetic or immunological blockade of TNF-alpha receptors. Muscle histology, contractile force generation, and myogenic gene expression will be determined to evaluate regeneration. Aim 3. To determine signaling events by which TNF-alpha stimulates myogenic differentiation. TNF-alpha stimulation of MEF2, SRF, and GATA-2, and the underlying signaling mechanisms will be evaluated. Our long-term objectives are to understand the role of cytokines as an emerging group of muscle regeneration modulators, and to improve the treatment of degenerative muscle diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RESCUE ANALYSIS OF UTROPHIN & NMJ SUPPORT BY SYNTROPHIN Principal Investigator & Institution: Sealock, Robert W.; Associate Professor; Cellular/Molecular Physiology; University of North Carolina Chapel Hill Aob 104 Airport Drive Cb#1350 Chapel Hill, Nc 27599 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 30-JUN-2007 Summary: (provided by applicant): The syntrophins are a family of peripheral membrane adapter proteins that function in association with dystrophin, utrophin, and the dystrobrevins, all of which are proteins of the surface membrane of skeletal muscle and implicated in the important human disease, Duchenne muscular dystrophy (DMD). Alpha-syntrophin is the major syntrophin in muscle. In the alpha-syntrophin knockout mouse, the postsynaptic membrane at the neuromuscular junction shows major biochemical and morphological defects including low amounts of acetylcholine receptors and acetylcholinesterase, a complete absence of utrophin, immature appearing contacts, junctional folds that are disorganized and few in number, and altered distribution of AChR. Thus, there is a utrophin and NMJ support function of alphasyntrophin. The first two aims of the project are to intended to extend current understanding that the other syntrophins of muscle (beta1, beta2, and probably gamma2) are not redundant with alpha-syntrophin. They are: 1) Test the hypothesis that transgenically expressed beta 1-syntrophin will restore utrophin to adult alphasyntrophin 4- junctions but will not rescue other, or all other, aspects of the phenotype. 2) Test the hypothesis that transgenically expressed beta 2-syntrophin will restore no aspects of the alpha-syntrophin -/- phenotype. The results will provide a solid framework for molecular analysis of the mechanisms of the support function. Aim 3) Identify the critical functional domains of the alpha-syntrophin molecule by transgenic expression in alpha-syntrophin -/- mice of a) chimeric proteins containing domains of beta substituted into alpha-syntrophin (or the converse, alpha into beta) and/or b) alpha-syntrophin specifically mutagenized at selected sites. The results will identify domains and implicate syntrophin-dependent pathways. Aim 4) Determine whether low levels of utrophin mRNA, inability of the membrane to accept utrophin incorporation, or both contribute to the lack of utrophin at alpha-syntrophin -/- NMJs. If applicable, use these tools to analyze the transgenic mice. 5) Seek to identify determinants in the AChR accumulation pathway-- AChR mRNA levels, total AChR expression, cell surface AChR expression, AChR clustering response to agrin, stability of agrin-induced clusters--that may contribute to the low AChR content of alphasyntrophin 4- NMJs. If applicable, use the understanding so generated to analyze the transgenic mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: RNA/PROTEIN REGULATION

INTERACTIONS

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PREMRNA

SPLICING

Principal Investigator & Institution: Singh, Ravinder; Molecular, Cellular & Dev Biol; University of Colorado at Boulder Boulder, Co 80309 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Sex determination is a fundamental decision that essentially all metazoans encounter during their development. Sex determination in Drosophila melanogaster involves a hierarchy of alternative splicing decisions, and is also the best understood example of splicing regulation. Splicing is a process by which non-coding sequences (introns) are removed from the precursor messenger RNA. In higher eukaryotes,

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constitutive and alternative splicing are important aspects of gene regulation in many important cellular processes. Approximately 15 percent of the mutations that have been linked to human diseases affect RNA splicing signals, including cellular transformation, Duchenne muscular dystrophy, and tumor metastasis. Our goal is to understand how RNA-binding proteins recognize target RNAs and regulate constitutive and alternative pre-mRNA splicing. The Drosophila protein Sex-lethal (SXL) acts as a key binary switch between the male and female cell fates. In the past, we defined the mechanism by which SXL regulates alternative splicing by antagonizing the known splicing factor U2AF65. Specificity is an underlying theme in biological regulation. U2AF65 and SXL offer excellent models for specific RNA-protein interactions in the context of splicing regulation. For example, while the general splicing factor U2AF65 recognizes a wide variety of polypyrimidine-tract/3' splice sites, the highly specific splicing repressor SXL recognizes a specific sequence. Although both proteins contain a ribonucleoproteinconsensus motif, they have distinct RNA-binding specificity. However, it is not understood how these seemingly similar proteins achieve unique RNA-binding specificities. To define the structural basis for the RNA-binding specificities of U2AF65 and SXL, we will extend our analysis of the RNA and the proteins by using a combination of biochemical, molecular, and genetic approaches. Our findings will also be directly applicable to other members of this largest family that likely regulate different aspects of RNA biogenesis. In addition, SXL controls many female-specific functions. However, some of the relevant genes that are regulated by SXL remain to be identified. To identify these targets, we will use a combination of recently developed molecular approaches - genomic SELEX and subtractive hybridization/differential display. These approaches should complement genetic analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SKELETAL MUSCLE STRUCTURE AND FUNCTION IN AGING MDX MICE Principal Investigator & Institution: Brooks, Susan V.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: The purpose is to investigate the function of dystrophin and the dystrophinassociated proteins (DAPs) in skeletal muscle fibers and how defects in the dystrophinDAP complex contribute to the pathological changes in muscle over the life span of mdx mice. The absence of dystrophin from the muscles of patients with Duchenne muscular dystrophy leads to ongoing muscle fiber degeneration, progressive necrosis, and fibrosis. Dystrophin is also absent from the muscles of mdx mice. The mechanisms underlying the degenerative process in dystrophic muscle are unknown, but replacement of dystrophin in transgenic-mdx mice prevents many of the dystrophic symptoms. In control animals, degeneration of myofibers may result from contractioninduced injury and susceptibility to contraction-induced injury than those in agematched control mice, but for muscles in transgenic-mdx mice the susceptibility to injury is not known, nor has the effect of age on contraction-induced injury been studied in mdx or transgenic mdx-mice. The working hypothesis are that (i) the dystrophin-DAP complex shunts contractile forces laterally from the myofibrils through the plasma membrane to the extracellular matrix, and a lack of dystrophin results in stress concentrations on the sarcolemma which damage the membrane, and a mechanically compromised cytoskeleton which increases sarcomere heterogeneity and damage; and (ii) the increased susceptibility to both sarcolemma and sarcomere damage is aggravated as animals age. Specific hypotheses have been formulated regarding the mechanical

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function of dystrophin and the effects of age on contraction- induced injury of dystrophic muscle fibers. Structure/function relationships of the dystrophin-DAP complex will be studied in single intact fibers from muscles of control, mdx, and transgenic-mdx mice, and contraction-induced injury will be studied using single fibers in vitro and whole muscles in situ from adult and old mice. Determining the function of dystrophin and why its absence is so devastating will contribute significantly to out understanding of the mechanisms underlying the wasting and weakness that occurs with dystrophy and with normal aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SPIRITUALITY OF CHILDREN WITH DMD Principal Investigator & Institution: Pehler, Shelley-Rae; None; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2003; Project Start 01-JAN-2004; Project End 31-DEC-2006 Summary: (provided by applicant): This application proposes research to explore the spirituality of an 8 -12 year old child with Duchenne Muscular Dystrophy. Duchenne Muscular Dystrophy (DMD) is a progressive, genetically inherited, chronic disease with a life-threatening prognosis. Early confirmation of the type of genetic disease a child has allows interventions to be initiated that may affect the quality and longevity of life. What is not known is the spirituality of children with a genetically inherited, life threatening disease, even though the literature is clear that there is a heightened spirituality in the adult and adolescent populations with similar diseases. This heightened spirituality has provided meaning to the adult and adolescents' life to promote healing. Healing does not mean cure in the usual use of the word, but instead a sense of health and well-being as experienced by hope, love, sense of control, relatedness with others, finding meaning and purpose in life and disease, and a sense that there is something greater than the self (Fryback, 1993; Mytko & Knight, 1999). The purpose of this study is to explore spirituality in children who are 8 -12 years of age and who have been diagnosed with the genetic, life-threatening disease of Duchenne Muscular Dystrophy. Giorgi's (1985) qualitative design will be used for this phenomenological study. Children 8 -12 years old with DMD will be recruited from a large, mid-western genetics clinic. Children will be invited to participate in the research until no new themes or meaning units are identified during the interviews. Interviews using open-ended questions and descriptions by the children of drawings they have made will elicit the data. Interview data will be transcribed to sheets of paper verbatim. Demographic information will be used to generate descriptive statistics for the sample population and to determine any religious belief systems that would help in the understanding of the child's responses to the questions. Analysis of the data will follow Giorgi's (1985) method of analysis. Rigor will be addressed through bracketing prior to interviewing and data analysis, using two different data collection strategies, development of a detailed Interview Schedule, using a peer debriefed, and developing an audit process for field notes and data analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SURGICAL APPROACHES TO SYSTEMIC GENE TRANSFER Principal Investigator & Institution: Stedman, Hansell H.; Assistant Professor; Surgery; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007

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Summary: (provided by applicant): The overall aim of the proposed research is to improve the prospects for therapeutic gene transfer in Duchenne muscular dystrophy by addressing two essential rate-limiting issues: immunity to the transgene product and vector delivery. Using a newly described canine animal model for Duchenne muscular dystrophy, the German Short Haired Pointer, the experimental design takes advantage of a deletion of the dystrophin gene to evaluate the comparative immunogenicity of dystrophin and utrophin. We make exclusive use of rAAV vectors. The experimental design tests the hypothesis that in the context of the deletion, recombinant (canine) mini-dystrophin will elicit a deleterious cellular immune response. It further tests the hypothesis that substitution of a similarly designed canine mini-utrophin transgene will circumvent this immune response. Based on extensive preliminary data, the proposal also addresses the hypothesis that the endothelial barrier to systemic gene delivery can be bypassed by temporarily infusing histamine during a period of mechanical circulatory support. We propose a graded series of experiments to address the latter hypothesis, starting with isolated limb perfusion and culminating in systemic gene delivery. These studies will also make extensive use of another naturally occurring animal model, the hamster model for limb-girdle muscular dystrophy. Successful completion of the experimental plan will provide general information relevant to the immunological response to somatic gene delivery and the preservation of organ function during profound but rapidly reversible alterations in endothelial integrity. It will also provide specific information about the rational design of strategies for systemic gene therapy in one of the most common single-gene lethal diseases in man, Duchenne Muscular Dystrophy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: TEST OF AAV VECTORS IN K9 DMD MODEL Principal Investigator & Institution: Little, Marie-Terese E.; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2003; Project Start 26-SEP-2003; Project End 31-JUL-2008 Summary: Duchenne Muscular Dystrophy (DMD) in both humans and dogs is a fatal, Xlinked, recessive muscle disease caused by a lack of dystrophin due to deletions or mutations in the dystrophin gene. The disease is inherited in a recessive pattern suggesting that gene therapy could offer an effective treatment if methods can be found to replace the defective gene in muscle. Studies in the mouse model ofDMD (mdx) have shown that delivery of mini-dystrophin adeno-associated viral (AAV) vectors, which display a remarkable ability to transduce skeletal muscle vectors to adult mdx muscle results in correction of most, but not all, features of dystrophy. Prior to launching into clinical trials with this vector system, data in a large animal model, which more closely reflects the disease phenotype in humans, are needed to assess the safety and effectiveness of this approach. Three specific hypotheses will be tested: 1) that an increase in muscle fiber integrity and function can be achieved by targeted direct injection of AAV vectors containing truncated canine dystrophin genes; 2) that wild type satellite cell transfer and vascularized muscle transplants will result in successful transfer and persistence of wild type satellite cells for the correction of the DMD phenotype; and 3) that seeding of wild type satellite cells will occur from normal to diseased muscle. Aims 1 and 2 will be conducted in recipients of marrow grafts to avoid potential rejection of wild type cells by the immune system. The canine model of DMD that is clinically and pathologically similar to human DMD will be used. These studies will provide baseline data for the development of a phase I clinical AAV gene therapy trial for DMD (Project 1). The long-term obiectives of the proposed research are to

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determine if direct AAV-dystrophin gene and cellular itransplant delivery ameliorates and reverses dystrophic pathology in xmd muscle and if this leads to normal myofiber morphology, histology, cell membrane integrity and function. The development of new therapies in the canine model could have immediate impact on the treatment of DMD patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THERAPEUTIC APPROACHES FOR MUSCULAR DYSTROPHY Principal Investigator & Institution: Spencer, Melissa J.; Assistant Professor; Duchenne Muscular Dystrophy Res Ctr; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 05-MAY-2000; Project End 30-APR-2007 Summary: (appended verbatim from investigator's abstract): Duchenne muscular dystrophy (DMD) is the most common, inherited, lethal disease of childhood. Despite its high frequency of occurrence and the extensive knowledge of the molecular genetics of DMD, the lifespan or quality of life of DMD children has not improved over that which existed before the mutant gene was discovered approximately 13 years ago. Recently, our laboratories have shown that the histologically discernible pathology of the muscles of mdx mice, the most widely used animal model of the disease, could be reduced by more than half through interventions that inhibit cytotoxic T lymphocytes (CTLs). This is the greatest systemic improvement in the pathology of dystrophic muscle attained by any intervention, and it indicates that important new avenues for approaching DMD therapeutics may exist. The general goal of the investigation proposed here is to obtain more specific information concerning the role of T Iymphocytes in the death of dystrophic muscle, so that more specific therapeutic interventions with applicability to humans can be developed in future work. This will be done by: 1) determining whether distinct populations of T lymphocytes function through independent mechanisms in the autoreactive killing of mdx muscle, 2) testing whether binding of costimulatory molecules that are involved in Tcell activation is important for activation of autoreactive Tcells in mdx mice, and whether simultaneous blockade of these molecules is maximally effective for treatment, 3) testing whether the blockade of costimulating molecu1es of Tcells in mdx mice is most effective at reducing muscle pathology when applied early in the disease process, and 4) testing whether treatment of utrophin deficient mdx mice through Tcell depletions or with blockers of Tcell costimulation is effective in reducing muscle pathology and extending lifespan. Collectively, these findings can provide the basis for design of immune interventions to reduce the pathology of dystrophin deficient muscle. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRANSLATIONAL RESEARCH IN THE DYSTROPHINOPATHIES Principal Investigator & Institution: Flanigan, Kevin M.; Associate Professor; Neurology; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD) are devastating disorders. Both are associated with mutations in the dystrophin gene, a huge gene with 79 exons spread over 2.4 million bases of genomic sequence. Deletions of large portions of the gene account for around 60% of all dystrophin mutations. The remainder consist of point mutations (primarily premature stop codon mutations), small deletions resulting in shift of the reading frame,

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and (in less than 5%) duplications. Dystrophin gene deletion testing is commercially and readily available, but point mutation testing is not. Recent studies in the mdx mouse, a model for DMD due to a premature stop codon mutation, have demonstrated the ability of aminoglycosides to increase the expression of dystrophin protein via induction of increased read-through. Recently, we and others have demonstrated some rules for the specificity of this effect, and a growing body of data suggests that aminoglycoside therapy may prove beneficial in some patients. We have developed the methodology to rapidly, robustly, and economically perform direct sequence analysis of the entire coding and regulatory regions of the dystrophin gene, greatly expediting the characterization of mutations in non-deleted dystrophinopathy patients. Using this methodology, we propose to characterize the mutations responsible for DMD and BMD in a large cohort of patients, from whom a standardized and thorough phenotypic characterization, will be obtained. Phenotype/genotype information will be compiled in a pilot dystrophinopathy registry database. Correlation of the phenotype to the sequence context of specific individual mutations will generate hypotheses of aminoglycoside-induced read-through efficiency in specific sequence contexts, which will be tested in an in vitro dual-luciferase transfection assay. This same assay will be used to systematically study other pharmaceutical compounds, which may cause readthrough of premature stop codon or frameshift mutations, and to study other potential mechanisms for modifying intrinsic frame shifting and read-through. Finally, we propose to develop a dual-GFP transgenic mouse, which will allow in vivo characterization of tissue-specific variation in aminoglycoside-induced read-through. Although we do not propose to perform an aminoglycoside treatment trial at present, this proposed study will identify a cohort of patients who may be candidates for any future trials here or at other institutions, and may provide a rationale to suggest that individual compounds or dosages may need to be tailored to specific sequence variations in all future trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Duchenne muscular 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 Duchenne muscular dystrophy in the PubMed Central database:

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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A 230kb cosmid walk in the Duchenne muscular dystrophy gene: detection of a conserved sequence and of a possible deletion prone region. by Heilig R, Lemaire C, Mandel JL.; 1987 Nov 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=306457

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A 71-Kilodalton Protein is a Major Product of the Duchenne Muscular Dystrophy Gene in Brain and Other Nonmuscle Tissues. by Lederfein D, Levy Z, Augier N, Mornet D, Morris G, Fuchs O, Yaffe D, Nudel U.; 1992 Jun 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=49288

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A second promoter provides an alternative target for therapeutic up-regulation of utrophin in Duchenne muscular dystrophy. by Burton EA, Tinsley JM, Holzfeind PJ, Rodrigues NR, Davies KE.; 1999 Nov 23; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24184

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Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. by Chamberlain JS, Gibbs RA, Ranier JE, Nguyen PN, Caskey CT.; 1988 Dec 9; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=339001

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Detection of Dystrophin in the Postsynaptic Density of Rat Brain and Deficiency in a Mouse Model of Duchenne Muscular Dystrophy. by Kim T, Wu K, Xu J, Black IB.; 1992 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=50609

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Direct analysis of amniotic fluid cells by multiplex PCR provides rapid prenatal diagnosis for Duchenne muscular dystrophy. by Simard LR, Gingras F, Labuda D.; 1991 May 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=329469

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Direct PCR from CVS and blood lysates for detection of cystic fibrosis and Duchenne muscular dystrophy deletions. by Balnaves ME, Nasioulas S, Dahl HH, Forrest S.; 1991 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=333801

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DNA amplification of a further exon of Duchenne muscular dystrophy locus increase possibilities for deletion screening. by Speer A, Rosenthal A, Billwitz H, Hanke R, Forrest SM, Love D, Davies KE, Coutelle C.; 1989 Jun 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318056

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Duchenne muscular dystrophy (DMD) gene cDNA 8 PstI and TaqI polymorphisms involve exon 51 of the HindIII map. by Laing NG, Akkari PA, Chandler DC, Thomas HE, Layton MG, Mears ME, Kakulas BA.; 1990 Jul 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=331223

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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. by Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG.; 2000 Dec 5; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=17659

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Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. by Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM.; 2002 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=137534

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Gene for OTC: characterisation and linkage to Duchenne muscular dystrophy. by Davies KE, Briand P, Ionasescu V, Ionasescu G, Williamson R, Brown C, Cavard C, Cathelineau L.; 1985 Jan 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340981

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Human X chromosome markers and Duchenne muscular dystrophy. by Davies KE, Speer A, Herrmann F, Spiegler AW, McGlade S, Hofker MH, Briand P, Hanke R, Schwartz M, Steinbicker V, et al.; 1985 May 24; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=341249

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Immunological identification of a high molecular weight protein as a candidate for the product of the Duchenne muscular dystrophy gene. by Kao L, Krstenansky J, Mendell J, Rammohan KW, Gruenstein E.; 1988 Jun; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=280456

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Isolation of a conserved sequence deleted in Duchenne muscular dystrophy patients. by Smith TJ, Wilson L, Kenwrick SJ, Forrest SM, Speer A, Coutelle C, Davies KE.; 1987 Mar 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=340624

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Linkage analysis of two cloned DNA sequences flanking the Duchenne muscular dystrophy locus on the short arm of the human X chromosome. by Davies KE, Pearson PL, Harper PS, Murray JM, O'Brien T, Sarfarazi M, Williamson R.; 1983 Apr 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=325885

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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. by Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, von Moers A, Morris GE, den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K.; 2002 Sep 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=151133

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Modulation of Myoblast Fusion by Caveolin-3 in Dystrophic Skeletal Muscle Cells: Implications for Duchenne Muscular Dystrophy and Limb-Girdle Muscular Dystrophy-1C. by Volonte D, Peoples AJ, Galbiati F.; 2003 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=207001

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MspI RFLP for Duchenne muscular dystrophy cDNA subclone 9. by Wagner M, Reiss J, Hentemann M, Thies U.; 1989 Apr 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317767

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NO skeletal muscle derived relaxing factor in Duchenne muscular dystrophy. by Bredt DS.; 1998 Dec 8; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=33925

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Non-operative treatment for perforated gastro-duodenal peptic ulcer in Duchenne Muscular Dystrophy: a case report. by Brinkman JM, Oddens JR, Van Royen BJ, Wever J, Olsman JG.; 2004; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324410

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RFLP for Duchenne muscular dystrophy cDNA clone 30-2. by Walker AP, Bartlett RJ, Laing NG, Siddique T, Yamaoka LH, Chen JC, Hung WY, Roses AD.; 1988 Sep 26; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338682

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RFLP for Duchenne muscular dystrophy cDNA clone 44-1. by Laing NG, Siddique T, Bartlett RJ, Yamaoka LH, Chen JC, Walker AP, Hung WY, Roses AD.; 1988 Jul 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=338389

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RFLP for HindIII at the Duchenne muscular dystrophy gene. by Prior TW, Friedman KJ, Silverman LM.; 1989 Mar 25; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=317618

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Social deprivation in Duchenne muscular dystrophy: population based study. by Bushby K, Raybould S, O'Donnell S, Steele JG.; 2001 Nov 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=59456

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The role of basal and myogenic factors in the transcriptional activation of utrophin promoter A: implications for therapeutic up-regulation in Duchenne muscular dystrophy. by Perkins KJ, Burton EA, Davies KE.; 2001 Dec 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=96689

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Two human cDNA molecules coding for the Duchenne muscular dystrophy (DMD) locus are highly homologous. by Rosenthal A, Speer A, Billwitz H, Cross GS, Forrest SM, Davies KE.; 1989 Jul 11; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=318130

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Duchenne muscular dystrophy, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Duchenne muscular dystrophy” (or synonyms) into the search box, and click “Go.” The

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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following is the type of output you can expect from PubMed for Duchenne muscular dystrophy (hyperlinks lead to article summaries): •

A comparison of the stress and coping strategies between the parents of children with Duchenne muscular dystrophy and children with a fever. Author(s): Chen JY, Chen SS, Jong YJ, Yang YH, Chang YY. Source: Journal of Pediatric Nursing. 2002 October; 17(5): 369-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395305&dopt=Abstract

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A descriptive epidemiological study of Duchenne muscular dystrophy in childhood in Estonia. Author(s): Talkop UA, Kahre T, Napa A, Talvik I, Soot A, Piirsoo A, Sander V, Talvik T. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2003; 7(5): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14511626&dopt=Abstract

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A new approach to the therapy of Duchenne muscular dystrophy with early precursors of myogenesis. Author(s): Sukhikh GT, Malaitsev VV, Bogdanova IM, Dubrovina IV, Sitnikov VF. Source: Bulletin of Experimental Biology and Medicine. 2001 December; 132(6): 1131-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12152867&dopt=Abstract

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A noninvasive means of detecting preclinical cardiomyopathy in Duchenne muscular dystrophy? Author(s): Towbin JA. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 317-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875770&dopt=Abstract

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Activation of nuclear factor-kappaB in inflammatory myopathies and Duchenne muscular dystrophy. Author(s): Monici MC, Aguennouz M, Mazzeo A, Messina C, Vita G. Source: Neurology. 2003 March 25; 60(6): 993-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654966&dopt=Abstract

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Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy. Author(s): Hayes JA, Ames WA. Source: British Journal of Anaesthesia. 2004 January; 92(1): 149; Author Reply 149-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14714277&dopt=Abstract

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Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy. Author(s): Schummer W, Schummer C. Source: British Journal of Anaesthesia. 2004 January; 92(1): 149; Author Reply 149-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14665570&dopt=Abstract

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Acute heart failure during spinal surgery in a boy with Duchenne muscular dystrophy. Author(s): Schmidt GN, Burmeister MA, Lilje C, Wappler F, Bischoff P. Source: British Journal of Anaesthesia. 2003 June; 90(6): 800-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12765898&dopt=Abstract

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Adequate tidal volume with row-a-boat phenomenon in advanced Duchenne muscular dystrophy. Author(s): Yasuma F, Kato T, Naya M. Source: Chest. 2002 May; 121(5): 1726. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006480&dopt=Abstract

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Advances in Duchenne muscular dystrophy gene therapy. Author(s): van Deutekom JC, van Ommen GJ. Source: Nature Reviews. Genetics. 2003 October; 4(10): 774-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14526374&dopt=Abstract

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Airway nitric oxide in Duchenne muscular dystrophy. Author(s): Straub V, Ratjen F, Amthor H, Voit T, Grasemann H. Source: The Journal of Pediatrics. 2002 July; 141(1): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12091865&dopt=Abstract

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Alpha-sarcoglycanopathy previously misdiagnosed as Duchenne muscular dystrophy: implications for current diagnostics and patient care. Author(s): Schara U, Gencik M, Mortier J, Langen M, Gencikova A, Epplen JT, Mortier W. Source: European Journal of Pediatrics. 2001 July; 160(7): 452-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11475588&dopt=Abstract

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Altered regional brain glucose metabolism in Duchenne muscular dystrophy: a pet study. Author(s): Lee JS, Pfund Z, Juhasz C, Behen ME, Muzik O, Chugani DC, Nigro MA, Chugani HT. Source: Muscle & Nerve. 2002 October; 26(4): 506-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12362416&dopt=Abstract

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Analysis of dystrophin mRNA from skeletal muscle but not from lymphocytes led to identification of a novel nonsense mutation in a carrier of Duchenne muscular dystrophy. Author(s): Ito T, Takeshima Y, Yagi M, Kamei S, Wada H, Nakamura H, Matsuo M. Source: Journal of Neurology. 2003 May; 250(5): 581-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12736738&dopt=Abstract

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Analysis of RFLPs and DNA deletions in the Chinese Duchenne muscular dystrophy gene. Author(s): Zeng YT, Chen MJ, Ren ZR, Qui XK, Huang SZ. Source: Journal of Medical Genetics. 1991 March; 28(3): 167-70. Erratum In: J Med Genet 1991 July; 28(7): 501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1675685&dopt=Abstract

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Antisense-induced multiexon skipping for Duchenne muscular dystrophy makes more sense. Author(s): Aartsma-Rus A, Janson AA, Kaman WE, Bremmer-Bout M, van Ommen GJ, den Dunnen JT, van Deutekom JC. Source: American Journal of Human Genetics. 2004 January; 74(1): 83-92. Epub 2003 December 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14681829&dopt=Abstract

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Are clinical trials of cell transplantation for Duchenne muscular dystrophy ethical? Author(s): Cho MK. Source: Irb. 1994 January-April; 16(1-2): 12-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11652321&dopt=Abstract

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Assessment of cardiac function in adolescents with Duchenne muscular dystrophy: importance of neurohormones. Author(s): Ramaciotti C, Scott WA, Lemler MS, Haverland C, Iannaccone ST. Source: Journal of Child Neurology. 2002 March; 17(3): 191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026234&dopt=Abstract

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Assessment of locomotor function in young boys with Duchenne muscular dystrophy. Author(s): Smith RA, Newcombe RG, Sibert JR, Harper PS. Source: Muscle & Nerve. 1991 May; 14(5): 462-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1870637&dopt=Abstract

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Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. Author(s): Alvarez K, Fadic R, Brandan E. Source: Journal of Cellular Biochemistry. 2002; 85(4): 703-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968010&dopt=Abstract

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Basilar artery occlusion in a case of Duchenne muscular dystrophy. Author(s): Matsuishi T, Yano E, Terasawa K, Nonaka I, Ishihara O, Yamaguchi Y, Okudera T. Source: Brain & Development. 1982; 4(5): 379-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7137515&dopt=Abstract

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Becker and Duchenne muscular dystrophy: a comparative morphological study. Author(s): Dennett X, Shield LK, Clingan LJ, Woolley DA. Source: Aust Paediatr J. 1988; 24 Suppl 1: 15-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3202735&dopt=Abstract

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Benign Duchenne muscular dystrophy in a patient with growth hormone deficiency: a five years follow-up. Author(s): Zatz M, Betti RT. Source: American Journal of Medical Genetics. 1986 July; 24(3): 567-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3728575&dopt=Abstract

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Birth and population prevalence of Duchenne muscular dystrophy in The Netherlands. Author(s): van Essen AJ, Busch HF, te Meerman GJ, ten Kate LP. Source: Human Genetics. 1992 January; 88(3): 258-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1733827&dopt=Abstract

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Bladder dysfunction in Duchenne muscular dystrophy. Author(s): MacLeod M, Kelly R, Robb SA, Borzyskowski M. Source: Archives of Disease in Childhood. 2003 April; 88(4): 347-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651768&dopt=Abstract

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Blind evaluation of lymphocyte capping in Duchenne muscular dystrophy. Author(s): Goldsmith BM, Drachman DB, Gruemer HD, Miller WG, Self SS. Source: Neurology. 1984 June; 34(6): 821-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6374498&dopt=Abstract

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Blood loss in Duchenne muscular dystrophy: vascular smooth muscle dysfunction? Author(s): Noordeen MH, Haddad FS, Muntoni F, Gobbi P, Hollyer JS, Bentley G. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 1999 July; 8(3): 212-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10399127&dopt=Abstract

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Body composition and energy expenditure in Duchenne muscular dystrophy. Author(s): Zanardi MC, Tagliabue A, Orcesi S, Berardinelli A, Uggetti C, Pichiecchio A. Source: European Journal of Clinical Nutrition. 2003 February; 57(2): 273-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12571659&dopt=Abstract

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Body composition determined with MR in patients with Duchenne muscular dystrophy, spinal muscular atrophy, and normal subjects. Author(s): Leroy-Willig A, Willig TN, Henry-Feugeas MC, Frouin V, Marinier E, Boulier A, Barzic F, Schouman-Claeys E, Syrota A. Source: Magnetic Resonance Imaging. 1997; 15(7): 737-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9309604&dopt=Abstract

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Bone mineral density and bone metabolism in Duchenne muscular dystrophy. Author(s): Bianchi ML, Mazzanti A, Galbiati E, Saraifoger S, Dubini A, Cornelio F, Morandi L. Source: Osteoporosis International : a Journal Established As Result of Cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the Usa. 2003 September; 14(9): 761-7. Epub 2003 July 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12897980&dopt=Abstract

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Bone mineral density and fractures in boys with Duchenne muscular dystrophy. Author(s): Larson CM, Henderson RC. Source: Journal of Pediatric Orthopedics. 2000 January-February; 20(1): 71-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641693&dopt=Abstract

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Botulinum toxin for amelioration of knee contracture in Duchenne muscular dystrophy. Author(s): von Wendt LO, Autti-Ramo IS. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1999; 3(4): 175-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10476367&dopt=Abstract

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Brain abnormalities in Duchenne muscular dystrophy: phosphorus-31 magnetic resonance spectroscopy and neuropsychological study. Author(s): Tracey I, Scott RB, Thompson CH, Dunn JF, Barnes PR, Styles P, Kemp GJ, Rae CD, Pike M, Radda GK. Source: Lancet. 1995 May 20; 345(8960): 1260-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7746055&dopt=Abstract

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Brain biochemistry in Duchenne muscular dystrophy: a 1H magnetic resonance and neuropsychological study. Author(s): Rae C, Scott RB, Thompson CH, Dixon RM, Dumughn I, Kemp GJ, Male A, Pike M, Styles P, Radda GK. Source: Journal of the Neurological Sciences. 1998 October 8; 160(2): 148-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9849797&dopt=Abstract

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Brain function in Duchenne muscular dystrophy. Author(s): Anderson JL, Head SI, Rae C, Morley JW. Source: Brain; a Journal of Neurology. 2002 January; 125(Pt 1): 4-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11834588&dopt=Abstract

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Brain morphology in Duchenne muscular dystrophy: a Golgi study. Author(s): Jagadha V, Becker LE. Source: Pediatric Neurology. 1988 March-April; 4(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3242516&dopt=Abstract

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Branched-chain ketoacids reduce muscle protein degradation in Duchenne muscular dystrophy. Author(s): Stewart PM, Walser M, Drachman DB. Source: Muscle & Nerve. 1982 March; 5(3): 197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7088016&dopt=Abstract

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Breathing patterns and HbSaO2 changes during nocturnal sleep in patients with Duchenne muscular dystrophy. Author(s): Manni R, Ottolini A, Cerveri I, Bruschi C, Zoia MC, Lanzi G, Tartara A. Source: Journal of Neurology. 1989 October; 236(7): 391-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2809640&dopt=Abstract

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Calcium currents and transients in co-cultured contracting normal and Duchenne muscular dystrophy human myotubes. Author(s): Imbert N, Vandebrouck C, Duport G, Raymond G, Hassoni AA, Constantin B, Cullen MJ, Cognard C. Source: The Journal of Physiology. 2001 July 15; 534(Pt. 2): 343-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454955&dopt=Abstract

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Cardiac involvement of female carrier of Duchenne muscular dystrophy. Author(s): Kamakura K. Source: Intern Med. 2000 January; 39(1): 2-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10674837&dopt=Abstract

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Cardiac transplantation in a Duchenne muscular dystrophy carrier. Author(s): Melacini P, Fanin M, Angelini A, Pegoraro E, Livi U, Danieli GA, Hoffman EP, Thiene G, Dalla Volta S, Angelini C. Source: Neuromuscular Disorders : Nmd. 1998 December; 8(8): 585-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10093066&dopt=Abstract

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Carrier detection and prenatal molecular diagnosis in a Duchenne muscular dystrophy family without any affected relative available. Author(s): Alcantara MA, Garcia-Cavazos R, Hernandez-U E, Gonzalez-del Angel A, Carnevale A, Orozco L. Source: Annales De Genetique. 2001 July-September; 44(3): 149-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694228&dopt=Abstract

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Cause of progression in Duchenne muscular dystrophy: impaired differentiation more probable than replicative aging. Author(s): Oexle K, Kohlschutter A. Source: Neuropediatrics. 2001 June; 32(3): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521207&dopt=Abstract

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cDNA microarray analysis of individual Duchenne muscular dystrophy patients. Author(s): Noguchi S, Tsukahara T, Fujita M, Kurokawa R, Tachikawa M, Toda T, Tsujimoto A, Arahata K, Nishino I. Source: Human Molecular Genetics. 2003 March 15; 12(6): 595-600. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12620965&dopt=Abstract

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Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Author(s): Phillips MF, Quinlivan RC, Edwards RH, Calverley PM. Source: American Journal of Respiratory and Critical Care Medicine. 2001 December 15; 164(12): 2191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11751186&dopt=Abstract

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Characterisation of dystrophin in carriers of Duchenne muscular dystrophy. Author(s): Clerk A, Rodillo E, Heckmatt JZ, Dubowitz V, Strong PN, Sewry CA. Source: Journal of the Neurological Sciences. 1991 April; 102(2): 197-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2072119&dopt=Abstract

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Clinical and experimental results on cardiac troponin expression in Duchenne muscular dystrophy. Author(s): Hammerer-Lercher A, Erlacher P, Bittner R, Korinthenberg R, Skladal D, Sorichter S, Sperl W, Puschendorf B, Mair J. Source: Clinical Chemistry. 2001 March; 47(3): 451-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11238296&dopt=Abstract

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Clinical implications of maximal respiratory pressure determinations for individuals with Duchenne muscular dystrophy. Author(s): Hahn A, Bach JR, Delaubier A, Renardel-Irani A, Guillou C, Rideau Y. Source: Archives of Physical Medicine and Rehabilitation. 1997 January; 78(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9014949&dopt=Abstract

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Coats' disease and Duchenne muscular dystrophy. Author(s): Bobart A, Brosnahan D. Source: Eye (London, England). 2001 August; 15(Pt 4): 563-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11767047&dopt=Abstract

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Collaborative translational research leading to multicenter clinical trials in Duchenne muscular dystrophy: the Cooperative International Neuromuscular Research Group (CINRG). Author(s): Escolar DM, Henricson EK, Pasquali L, Gorni K, Hoffman EP. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S147-154. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206809&dopt=Abstract

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Complete skipping of exon 66 due to novel mutations of the dystrophin gene was identified in two Japanese families of Duchenne muscular dystrophy with severe mental retardation. Author(s): Wibawa T, Takeshima Y, Mitsuyoshi I, Wada H, Surono A, Nakamura H, Matsuo M. Source: Brain & Development. 2000 March; 22(2): 107-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722962&dopt=Abstract

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Contiguous gene deletion syndrome involving glycerol kinase and Duchenne muscular dystrophy loci. Author(s): Asghar M, Nevin NC, Beattie ED, McManus D, Roberts GM, Phillips JA. Source: Journal of Inherited Metabolic Disease. 1999 December; 22(8): 933-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10604146&dopt=Abstract

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Contrasting evolutionary histories of two introns of the duchenne muscular dystrophy gene, Dmd, in humans. Author(s): Nachman MW, Crowell SL. Source: Genetics. 2000 August; 155(4): 1855-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924480&dopt=Abstract

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Correlation between progression of spinal deformity and pulmonary function in Duchenne muscular dystrophy. Author(s): Yamashita T, Kanaya K, Yokogushi K, Ishikawa Y, Minami R. Source: Journal of Pediatric Orthopedics. 2001 January-February; 21(1): 113-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11176364&dopt=Abstract

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Correlation of laboratory and clinical findings with the location of Xp21 deletion in Duchenne muscular dystrophy. Author(s): Tasdemir HA, Topaloglu H, Dincer P, Gogus S, Kotiloglu E, Ozdirim E, Yalaz K. Source: Turk J Pediatr. 1997 July-September; 39(3): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9339110&dopt=Abstract

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Correlation of muscle fiber type measurements with clinical and molecular genetic data in Duchenne muscular dystrophy. Author(s): Wang JF, Forst J, Schroder S, Schroder JM. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 150-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382908&dopt=Abstract

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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Wong BL, Christopher C. Source: Journal of Child Neurology. 2002 March; 17(3): 183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026233&dopt=Abstract

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Creatine kinase, cell membrane and Duchenne muscular dystrophy. Author(s): Ozawa E, Hagiwara Y, Yoshida M. Source: Molecular and Cellular Biochemistry. 1999 January; 190(1-2): 143-51. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10098981&dopt=Abstract

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De novo mutations in sporadic deletional Duchenne muscular dystrophy (DMD) cases. Author(s): Mukherjee M, Chaturvedi LS, Srivastava S, Mittal RD, Mittal B. Source: Experimental & Molecular Medicine. 2003 April 30; 35(2): 113-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12754415&dopt=Abstract

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Denaturing gradient gel electrophoresis (DGGE) for mutation detection in Duchenne muscular dystrophy (DMD). Author(s): Dolinsky LC. Source: Methods in Molecular Biology (Clifton, N.J.). 2003; 217: 165-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12491931&dopt=Abstract

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Dental characteristics of patients with Duchenne muscular dystrophy. Author(s): Symons AL, Townsend GC, Hughes TE. Source: Asdc J Dent Child. 2002 September-December; 69(3): 277-83, 234. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613312&dopt=Abstract

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Detection of glucocorticoid-like activity in traditional Chinese medicine used for the treatment of Duchenne muscular dystrophy. Author(s): Courdier-Fruh I, Barman L, Wettstein P, Meier T. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561491&dopt=Abstract

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Detection of point mutation in dystrophin gene reveals somatic and germline mosaicism in the mother of a patient with Duchenne muscular dystrophy. Author(s): van Essen AJ, Mulder IM, van der Vlies P, van der Hout AH, Buys CH, Hofstra RM, den Dunnen JT. Source: American Journal of Medical Genetics. 2003 April 30; 118A(3): 296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12673664&dopt=Abstract

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Diaphragm kinetics during pneumatic belt respiratory assistance: a sonographic study in Duchenne muscular dystrophy. Author(s): Ayoub J, Milane J, Targhetta R, Prioux J, Chamari K, Arbeille P, Jonquet O, Bourgeois JM, Prefaut C. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 569-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117482&dopt=Abstract

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Direct analysis of amniotic fluid cells by multiplex PCR provides rapid prenatal diagnosis for Duchenne muscular dystrophy. Author(s): Simard LR, Gingras F, Labuda D. Source: Nucleic Acids Research. 1991 May 11; 19(9): 2501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2041789&dopt=Abstract

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Direct deletion analysis in two Duchenne muscular dystrophy symptomatic females using polymorphic dinucleotide (CA)n loci within the dystrophin gene. Author(s): Giliberto F, Ferreiro V, Dalamon V, Surace E, Cotignola J, Esperante S, Borelina D, Baranzini S, Szijan I. Source: J Biochem Mol Biol. 2003 March 31; 36(2): 179-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689516&dopt=Abstract

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Direct PCR from CVS and blood lysates for detection of cystic fibrosis and Duchenne muscular dystrophy deletions. Author(s): Balnaves ME, Nasioulas S, Dahl HH, Forrest S. Source: Nucleic Acids Research. 1991 March 11; 19(5): 1155. Erratum In: Nucleic Acids Res 1991 May 11; 19(9): 2537. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2020553&dopt=Abstract

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Domiciliary investigation of sleep-related hypoxaemia in Duchenne muscular dystrophy. Author(s): Carroll N, Bain RJ, Smith PE, Saltissi S, Edwards RH, Calverley PM. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1991 April; 4(4): 434-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1855572&dopt=Abstract

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Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy. Author(s): Topin N, Matecki S, Le Bris S, Rivier F, Echenne B, Prefaut C, Ramonatxo M. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 576-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117483&dopt=Abstract

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Duchenne muscular dystrophy in a female child. Author(s): Viswanathan V. Source: Indian Pediatrics. 2002 October; 39(10): 980-1; Author Reply 981. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12428052&dopt=Abstract

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Duchenne muscular dystrophy. Author(s): Metules T. Source: Rn. 2002 October; 65(10): 39-44, 47; Quiz 48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12432710&dopt=Abstract

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Duchenne muscular dystrophy: current knowledge, treatment, and future prospects. Author(s): Biggar WD, Klamut HJ, Demacio PC, Stevens DJ, Ray PN. Source: Clinical Orthopaedics and Related Research. 2002 August; (401): 88-106. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151886&dopt=Abstract

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Duchenne muscular dystrophy: hopes for the sesquicentenary. Author(s): Byrne E, Kornberg AJ, Kapsa R. Source: The Medical Journal of Australia. 2003 November 3; 179(9): 463-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14583075&dopt=Abstract

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Duchenne muscular dystrophy: prolongation of life by noninvasive ventilation and mechanically assisted coughing. Author(s): Gomez-Merino E, Bach JR. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 June; 81(6): 411-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023596&dopt=Abstract

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Duchenne muscular dystrophy--a molecular service. Author(s): Ballo R, Hitzeroth HW, Beighton PH. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1991 February 16; 79(4): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1671720&dopt=Abstract

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Duchenne muscular dystrophy--parental perceptions. Author(s): Bothwell JE, Dooley JM, Gordon KE, MacAuley A, Camfield PR, MacSween J. Source: Clinical Pediatrics. 2002 March; 41(2): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931326&dopt=Abstract

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Duchenne muscular dystrophy-rhabdomyosarcoma, ichthyosis vulgaris/acute monoblastic leukemia: association of rare genetic disorders and childhood malignant diseases. Author(s): Jakab Z, Szegedi I, Balogh E, Kiss C, Olah E. Source: Medical and Pediatric Oncology. 2002 July; 39(1): 66-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116087&dopt=Abstract

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Dystrophin gene deletions in South Indian Duchenne muscular dystrophy patients. Author(s): Mallikarjuna Rao GN, Hussain T, Geetha Devi N, Jain S, Chandak GR, Ananda Raj MP. Source: Indian Journal of Medical Sciences. 2003 January; 57(1): 1-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14514278&dopt=Abstract

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Early decrease of IIx myosin heavy chain transcripts in Duchenne muscular dystrophy. Author(s): Pedemonte M, Sandri C, Schiaffino S, Minetti C. Source: Biochemical and Biophysical Research Communications. 1999 February 16; 255(2): 466-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10049732&dopt=Abstract

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Early diagnosis in Duchenne muscular dystrophy. Author(s): Zalaudek I, Bonelli RM, Koltringer P, Reisecker F, Wagner K. Source: Lancet. 1999 June 5; 353(9168): 1975. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10371601&dopt=Abstract

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Early diagnosis of Duchenne muscular dystrophy with high level of transaminases. Author(s): Kurul S, Ulgenalp A, Dirik E, Ercal D. Source: Indian Pediatrics. 2002 February; 39(2): 210-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867860&dopt=Abstract

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Early diagnosis of Duchenne muscular dystrophy. Author(s): Appleton RE, Nicolaides P. Source: Lancet. 1995 May 13; 345(8959): 1243-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7739330&dopt=Abstract

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Early prednisone treatment in Duchenne muscular dystrophy. Author(s): Merlini L, Cicognani A, Malaspina E, Gennari M, Gnudi S, Talim B, Franzoni E. Source: Muscle & Nerve. 2003 February; 27(2): 222-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12548530&dopt=Abstract

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Early symptoms of Duchenne muscular dystrophy--description of cases of an 18month-old and an 8-year-old patient. Author(s): Iwanczak F, Stawarski A, Potyrala M, Siedlecka-Dawidko J, Agrawal GS. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 May-June; 6(3): 592-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11208376&dopt=Abstract

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Early treatment to preserve quality of locomotion for children with Duchenne muscular dystrophy. Author(s): Rideau Y, Duport G, Delaubier A, Guillou C, Renardel-Irani A, Bach JR. Source: Seminars in Neurology. 1995 March; 15(1): 9-17. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7638464&dopt=Abstract

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Effect of spinal surgery on lung function in Duchenne muscular dystrophy. Author(s): Kennedy JD, Staples AJ, Brook PD, Parsons DW, Sutherland AD, Martin AJ, Stern LM, Foster BK. Source: Thorax. 1995 November; 50(11): 1173-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8553273&dopt=Abstract

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Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Author(s): Silversides CK, Webb GD, Harris VA, Biggar DW. Source: The American Journal of Cardiology. 2003 March 15; 91(6): 769-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633823&dopt=Abstract

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Elevated basic fibroblast growth factor in the serum of patients with Duchenne muscular dystrophy. Author(s): D'Amore PA, Brown RH Jr, Ku PT, Hoffman EP, Watanabe H, Arahata K, Ishihara T, Folkman J. Source: Annals of Neurology. 1994 March; 35(3): 362-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8122890&dopt=Abstract

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Enhanced urinary spontaneous luminescence in Duchenne muscular dystrophy. Author(s): Reyes J, Salim-Hanna M, Lissi EA, Videla LA, Holmgren J. Source: Free Radical Biology & Medicine. 1994 June; 16(6): 851-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8070691&dopt=Abstract

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ERG phenotype of a dystrophin mutation in heterozygous female carriers of Duchenne muscular dystrophy. Author(s): Fitzgerald KM, Cibis GW, Gettel AH, Rinaldi R, Harris DJ, White RA. Source: Journal of Medical Genetics. 1999 April; 36(4): 316-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227401&dopt=Abstract

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Establishment of long-term myogenic cultures from patients with Duchenne muscular dystrophy by retroviral transduction of a temperature-sensitive SV40 large T antigen. Author(s): Simon LV, Beauchamp JR, O'Hare M, Olsen I. Source: Experimental Cell Research. 1996 May 1; 224(2): 264-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8612703&dopt=Abstract

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Evaluation of a program for long-term treatment of Duchenne muscular dystrophy. Experience at the University Hospitals of Cleveland. Author(s): Vignos PJ, Wagner MB, Karlinchak B, Katirji B. Source: The Journal of Bone and Joint Surgery. American Volume. 1996 December; 78(12): 1844-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8986661&dopt=Abstract

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Evaluation of microchip electrophoresis as a molecular diagnostic method for Duchenne muscular dystrophy. Author(s): Ferrance J, Snow K, Landers JP. Source: Clinical Chemistry. 2002 February; 48(2): 380-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11805028&dopt=Abstract

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Examination of telomere lengths in muscle tissue casts doubt on replicative aging as cause of progression in Duchenne muscular dystrophy. Author(s): Oexle K, Zwirner A, Freudenberg K, Kohlschutter A, Speer A. Source: Pediatric Research. 1997 August; 42(2): 226-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9262227&dopt=Abstract

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Expression and localization of protein inhibitor of neuronal nitric oxide synthase in Duchenne muscular dystrophy. Author(s): Guo Y, Petrof BJ, Hussain SN. Source: Muscle & Nerve. 2001 November; 24(11): 1468-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745948&dopt=Abstract

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Expression of dystrophin-associated glycoproteins and utrophin in carriers of Duchenne muscular dystrophy. Author(s): Sewry CA, Matsumura K, Campbell KP, Dubowitz V. Source: Neuromuscular Disorders : Nmd. 1994 September-November; 4(5-6): 401-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7881285&dopt=Abstract

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Expression of heat-shock/stress proteins in Duchenne muscular dystrophy. Author(s): Bornman L, Polla BS, Lotz BP, Gericke GS. Source: Muscle & Nerve. 1995 January; 18(1): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7799995&dopt=Abstract

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Expression of human full-length and minidystrophin in transgenic mdx mice: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Wells DJ, Wells KE, Asante EA, Turner G, Sunada Y, Campbell KP, Walsh FS, Dickson G. Source: Human Molecular Genetics. 1995 August; 4(8): 1245-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581360&dopt=Abstract

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Failure of early diagnosis in symptomatic Duchenne muscular dystrophy. Author(s): Bushby KM, Hill A, Steele JG. Source: Lancet. 1999 February 13; 353(9152): 557-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10028989&dopt=Abstract

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Failure to thrive in Duchenne muscular dystrophy. Author(s): Call G, Ziter FA. Source: The Journal of Pediatrics. 1985 June; 106(6): 939-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3998951&dopt=Abstract

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Fast muscle fibers are preferentially affected in Duchenne muscular dystrophy. Author(s): Webster C, Silberstein L, Hays AP, Blau HM. Source: Cell. 1988 February 26; 52(4): 503-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3342447&dopt=Abstract

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Fatal air embolism in an adolescent with Duchenne muscular dystrophy during Harrington instrumentation. Author(s): Lang SA, Duncan PG, Dupuis PR. Source: Anesthesia and Analgesia. 1989 July; 69(1): 132-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2742178&dopt=Abstract

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Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys. Author(s): Law PK, Goodwin TG, Fang Q, Duggirala V, Larkin C, Florendo JA, Kirby DS, Deering MB, Li HJ, Chen M, et al. Source: Cell Transplantation. 1992; 1(2-3): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1344295&dopt=Abstract

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Female carriers of Duchenne muscular dystrophy: a dilemma. Author(s): Isaacs H, Badenhorst M. Source: Clinical Genetics. 1987 May; 31(5): 288-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3608214&dopt=Abstract

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Fetal muscle biopsy as a diagnostic tool in Duchenne muscular dystrophy. Author(s): Nevo Y, Shomrat R, Yaron Y, Orr-Urtreger A, Harel S, Legum C. Source: Prenatal Diagnosis. 1999 October; 19(10): 921-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10521816&dopt=Abstract

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First meeting of the Duchenne Parent Project in Europe: Treatment of Duchenne Muscular Dystrophy. 7-8 November 1997, Rotterdam, The Netherlands. Author(s): Scheuerbrandt G. Source: Neuromuscular Disorders : Nmd. 1998 May; 8(3-4): 213-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9631405&dopt=Abstract

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Force plate studies of Duchenne muscular dystrophy. Author(s): Khodadadeh S, McClelland M, Patrick JH. Source: Eng Med. 1987 July; 16(3): 177-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3678573&dopt=Abstract

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Four novel dystrophin point mutations: detection by protein truncation test and transcript analysis in lymphocytes from Duchenne muscular dystrophy patients. Author(s): Tuffery S, Bareil C, Demaille J, Claustres M. Source: European Journal of Human Genetics : Ejhg. 1996; 4(3): 143-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8840114&dopt=Abstract

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Fracture prevalence in Duchenne muscular dystrophy. Author(s): McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG. Source: Developmental Medicine and Child Neurology. 2002 October; 44(10): 695-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12418795&dopt=Abstract

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Fractures in Duchenne muscular dystrophy--chiefly about their causes. Author(s): Hatano E, Masuda K, Kameo H. Source: Hiroshima J Med Sci. 1986 December; 35(4): 429-33. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3570852&dopt=Abstract

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Frameshift deletions of exons 3-7 and revertant fibers in Duchenne muscular dystrophy: mechanisms of dystrophin production. Author(s): Winnard AV, Mendell JR, Prior TW, Florence J, Burghes AH. Source: American Journal of Human Genetics. 1995 January; 56(1): 158-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7825572&dopt=Abstract

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Frameshift duplication resulting in truncated dystrophin in a patient with Duchenne muscular dystrophy. Author(s): Hu X, Bulman DE, Ray PN, Worton RG. Source: Human Mutation. 1992; 1(2): 172-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1301205&dopt=Abstract

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Free cytoplasmic Ca++ at rest and after cholinergic stimulus is increased in cultured muscle cells from Duchenne muscular dystrophy patients. Author(s): Mongini T, Ghigo D, Doriguzzi C, Bussolino F, Pescarmona G, Pollo B, Schiffer D, Bosia A. Source: Neurology. 1988 March; 38(3): 476-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3347352&dopt=Abstract

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Freeze-fracture analysis of plasma membranes in Duchenne muscular dystrophy. A study using cultured skin fibroblasts. Author(s): Jones GE, Severs NJ, Witkowski JA. Source: Journal of the Neurological Sciences. 1983 February; 58(2): 185-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6300339&dopt=Abstract

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Frequency and distribution of deletions in dystrophin gene in Duchenne muscular dystrophy patients from an east-European Slavonic population. Author(s): Kadasi L, Gecz J, Saksova L. Source: Gene Geogr. 1991 December; 5(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1841599&dopt=Abstract

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Functional involvement of cerebral cortex in Duchenne muscular dystrophy. Author(s): Di Lazzaro V, Restuccia D, Servidei S, Nardone R, Oliviero A, Profice P, Mangiola F, Tonali P, Rothwell JC. Source: Muscle & Nerve. 1998 May; 21(5): 662-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9572251&dopt=Abstract

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Functional muscle ischemia in neuronal nitric oxide synthase-deficient skeletal muscle of children with Duchenne muscular dystrophy. Author(s): Sander M, Chavoshan B, Harris SA, Iannaccone ST, Stull JT, Thomas GD, Victor RG. Source: Proceedings of the National Academy of Sciences of the United States of America. 2000 December 5; 97(25): 13818-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11087833&dopt=Abstract

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Functional significance of dystrophin positive fibres in Duchenne muscular dystrophy. Author(s): Nicholson LV, Johnson MA, Bushby KM, Gardner-Medwin D. Source: Archives of Disease in Childhood. 1993 May; 68(5): 632-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8323331&dopt=Abstract

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Gait and posture changes in the Duchenne muscular dystrophy child. Author(s): Hsu JD, Furumasu J. Source: Clinical Orthopaedics and Related Research. 1993 March; (288): 122-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8458124&dopt=Abstract

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Gene expression comparison of biopsies from Duchenne muscular dystrophy (DMD) and normal skeletal muscle. Author(s): Haslett JN, Sanoudou D, Kho AT, Bennett RR, Greenberg SA, Kohane IS, Beggs AH, Kunkel LM. Source: Proceedings of the National Academy of Sciences of the United States of America. 2002 November 12; 99(23): 15000-5. Epub 2002 Nov 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415109&dopt=Abstract

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Gene expression profiling of Duchenne muscular dystrophy skeletal muscle. Author(s): Haslett JN, Sanoudou D, Kho AT, Han M, Bennett RR, Kohane IS, Beggs AH, Kunkel LM. Source: Neurogenetics. 2003 August; 4(4): 163-71. Epub 2003 April 16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698323&dopt=Abstract

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Gene therapy in Duchenne muscular dystrophy. Author(s): Inui K, Okada S, Dickson G. Source: Brain & Development. 1996 September-October; 18(5): 357-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8891229&dopt=Abstract

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Gene therapy in man and mice: adenosine deaminase deficiency, ornithine transcarbamylase deficiency, and Duchenne muscular dystrophy. Author(s): Grompe M, Mitani K, Lee CC, Jones SN, Caskey CT. Source: Advances in Experimental Medicine and Biology. 1991; 309B: 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1781405&dopt=Abstract

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Gene therapy of Duchenne muscular dystrophy. Author(s): Fassati A, Murphy S, Dickson G. Source: Adv Genet. 1997; 35: 117-53. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9348647&dopt=Abstract

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Gene therapy prospects for Duchenne muscular dystrophy. Author(s): Clemens PR, Caskey CT. Source: European Neurology. 1994; 34(4): 181-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8082675&dopt=Abstract

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Gene-deletion and carrier detections, and prenatal diagnosis of Duchenne muscular dystrophy by analysis of the dystrophin gene amplified by polymerase chain reaction. Author(s): Fujishita S, Shibuya N, Niikawa N, Nagataki S. Source: Jinrui Idengaku Zasshi. 1991 December; 36(4): 317-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1811098&dopt=Abstract

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Genetic and biochemical normalization in female carriers of Duchenne muscular dystrophy: evidence for failure of dystrophin production in dystrophin-competent myonuclei. Author(s): Pegoraro E, Schimke RN, Garcia C, Stern H, Cadaldini M, Angelini C, Barbosa E, Carroll J, Marks WA, Neville HE. Source: Neurology. 1995 April; 45(4): 677-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7723955&dopt=Abstract

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Genetic counseling for childless women at risk for Duchenne muscular dystrophy. Author(s): Eggers S, Pavanello RC, Passos-Bueno MR, Zatz M. Source: American Journal of Medical Genetics. 1999 October 29; 86(5): 447-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10508987&dopt=Abstract

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Genetic counseling of isolated carriers of Duchenne muscular dystrophy. Author(s): Hoffman EP, Pegoraro E, Scacheri P, Burns RG, Taber JW, Weiss L, Spiro A, Blattner P. Source: American Journal of Medical Genetics. 1996 June 28; 63(4): 573-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8826437&dopt=Abstract

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Genetic risk: women's understanding of carrier risks in Duchenne muscular dystrophy. Author(s): Parsons EP, Clarke AJ. Source: Journal of Medical Genetics. 1993 July; 30(7): 562-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8411028&dopt=Abstract

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Genotype and electroretinal heterogeneity in Duchenne muscular dystrophy. Author(s): Ino-ue M, Honda S, Nishio H, Matsuo M, Nakamura H, Yamamoto M. Source: Experimental Eye Research. 1997 December; 65(6): 861-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9441711&dopt=Abstract

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Germinal mosaicism from grand-paternal origin in a family with Duchenne muscular dystrophy. Author(s): Claustres M, Kjellberg P, Desgeorges M, Bellet H, Demaille J. Source: Human Genetics. 1990 December; 86(2): 241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1979959&dopt=Abstract

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Germinal mosaicism in a Duchenne muscular dystrophy family: implications for genetic counselling. Author(s): Melis MA, Cau M, Congiu R, Puddu R, Muntoni F, Cao A. Source: Clinical Genetics. 1993 May; 43(5): 247-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8375105&dopt=Abstract

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Germinal mosaicism in Duchenne muscular dystrophy. Author(s): Wood S, McGillivray BC. Source: Human Genetics. 1988 March; 78(3): 282-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3346017&dopt=Abstract

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Germinal mosaicism increases the recurrence risk for 'new' Duchenne muscular dystrophy mutations. Author(s): Bakker E, Veenema H, Den Dunnen JT, van Broeckhoven C, Grootscholten PM, Bonten EJ, van Ommen GJ, Pearson PL. Source: Journal of Medical Genetics. 1989 September; 26(9): 553-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2810338&dopt=Abstract

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Germline and somatic mosaicism in a female carrier of Duchenne muscular dystrophy. Author(s): Bunyan DJ, Robinson DO, Collins AL, Cockwell AE, Bullman HM, Whittaker PA. Source: Human Genetics. 1994 May; 93(5): 541-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8168831&dopt=Abstract

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Glucose, free fatty acid and ketone body metabolism in Duchenne muscular dystrophy. Author(s): Nishio H, Wada H, Matsuo T, Horikawa H, Takahashi K, Nakajima T, Matsuo M, Nakamura H. Source: Brain & Development. 1990; 12(4): 390-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2240459&dopt=Abstract

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Glutathione depletion during experimental damage to rat skeletal muscle and its relevance to Duchenne muscular dystrophy. Author(s): Jackson MJ, Brooke MH, Kaiser K, Edwards RH. Source: Clinical Science (London, England : 1979). 1991 June; 80(6): 559-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1647917&dopt=Abstract

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Head circumference and intellectual performance of patients with Duchenne muscular dystrophy. Author(s): Appleton RE, Bushby K, Gardner-Medwin D, Welch J, Kelly PJ. Source: Developmental Medicine and Child Neurology. 1991 October; 33(10): 884-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1743411&dopt=Abstract

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Height and clinical course of Duchenne muscular dystrophy. Author(s): Coakley JH, Griffiths RD, Edwards RH. Source: American Journal of Medical Genetics. 1989 April; 32(4): 552-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2774003&dopt=Abstract

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High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Author(s): Connolly AM, Schierbecker J, Renna R, Florence J. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 917-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467746&dopt=Abstract

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High-resolution banding study of an X/4 translocation in a female with Duchenne muscular dystrophy. Author(s): Saito F, Tonomura A, Kimura S, Misugi N, Sugita H. Source: Human Genetics. 1985; 71(4): 370-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4077054&dopt=Abstract

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Hip subluxation and dislocation in Duchenne muscular dystrophy. Author(s): Chan KG, Galasko CS, Delaney C. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2001 July; 10(3): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497366&dopt=Abstract

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Histochemical fibre typing and ultrastructure of the small fibres in Duchenne muscular dystrophy. Author(s): Watkins SC, Cullen MJ. Source: Neuropathology and Applied Neurobiology. 1985 November-December; 11(6): 447-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2936970&dopt=Abstract

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HLA phenotypes in children with Duchenne muscular dystrophy and their gene carrier mothers. Author(s): Laszlo A, Kaiser G. Source: Acta Paediatr Hung. 1983; 24(4): 323-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6608950&dopt=Abstract

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HLA-A & HLA-B antigens in multiple sclerosis, motor neuron disease & Duchenne muscular dystrophy. Author(s): Mehta MM, Chablani UA, Contractor NM, Bhatia HM, Singhal BS, Mondkar VP, Desai AD. Source: The Indian Journal of Medical Research. 1986 May; 83: 519-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3733208&dopt=Abstract

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Hot spot of recombination within DXS164 in the Duchenne muscular dystrophy gene. Author(s): Grimm T, Muller B, Dreier M, Kind E, Bettecken T, Meng G, Muller CR. Source: American Journal of Human Genetics. 1989 September; 45(3): 368-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2570527&dopt=Abstract

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Human molecular genetics and the elucidation of the primary biochemical defect in Duchenne muscular dystrophy. Author(s): Hoffman EP. Source: Cell Motility and the Cytoskeleton. 1989; 14(1): 163-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2684423&dopt=Abstract

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Human ornithine transcarbamylase locus mapped to band Xp21.1 near the Duchenne muscular dystrophy locus. Author(s): Lindgren V, de Martinville B, Horwich AL, Rosenberg LE, Francke U. Source: Science. 1984 November 9; 226(4675): 698-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6494904&dopt=Abstract

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Human X chromosome markers and Duchenne muscular dystrophy. Author(s): Davies KE, Speer A, Herrmann F, Spiegler AW, McGlade S, Hofker MH, Briand P, Hanke R, Schwartz M, Steinbicker V, et al. Source: Nucleic Acids Research. 1985 May 24; 13(10): 3419-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3859837&dopt=Abstract

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Hypercapnia in relation to pulmonary function in Duchenne muscular dystrophy. Author(s): Canny GJ, Szeinberg A, Koreska J, Levison H. Source: Pediatric Pulmonology. 1989; 6(3): 169-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2497432&dopt=Abstract

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Hyperkalaemic cardiac arrest in a manifesting carrier of Duchenne muscular dystrophy following general anaesthesia. Author(s): Kerr TP, Duward A, Hodgson SV, Hughes E, Robb SA. Source: European Journal of Pediatrics. 2001 September; 160(9): 579-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11585084&dopt=Abstract

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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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920538&dopt=Abstract

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Hypersensitivity to DNA-damaging agents in abiotrophies: a new explanation for degeneration of neurons, photoreceptors, and muscle in Alzheimer, Parkinson and Huntington diseases, retinitis pigmentosa, and Duchenne muscular dystrophy. Author(s): Robbins JH, Brumback RA, Polinsky RJ, Wirtschafter JD, Tarone RE, Scudiero DA, Otsuka F. Source: Basic Life Sci. 1985; 35: 315-44. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2933027&dopt=Abstract

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Hypersensitivity to DNA-damaging agents in cultured cells from patients with Usher's syndrome and Duchenne muscular dystrophy. Author(s): Robbins JH, Scudiero DA, Otsuka F, Tarone RE, Brumback RA, Wirtschafter JD, Polinsky RJ, Barrett SF, Moshell AN, Scarpinato RG, et al. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1984 April; 47(4): 391-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6726265&dopt=Abstract

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Hypokalemia complicating Duchenne muscular dystrophy. Author(s): McDonald B, Rosenthal SA. Source: Yale J Biol Med. 1987 September-October; 60(5): 405-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3424874&dopt=Abstract

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Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Imbert N, Vandebrouck C, Constantin B, Duport G, Guillou C, Cognard C, Raymond G. Source: Neuromuscular Disorders : Nmd. 1996 October; 6(5): 351-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938699&dopt=Abstract

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Hypoxemia during sleep in Duchenne muscular dystrophy. Author(s): Smith PE, Calverley PM, Edwards RH. Source: Am Rev Respir Dis. 1988 April; 137(4): 884-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3354996&dopt=Abstract

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Identification and quantification of somatic mosaicism for a point mutation in a Duchenne muscular dystrophy family. Author(s): Smith TA, Yau SC, Bobrow M, Abbs SJ. Source: Journal of Medical Genetics. 1999 April; 36(4): 313-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10227400&dopt=Abstract

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Identification of altered gene expression in skeletal muscles from Duchenne muscular dystrophy patients. Author(s): Tkatchenko AV, Pietu G, Cros N, Gannoun-Zaki L, Auffray C, Leger JJ, Dechesne CA. Source: Neuromuscular Disorders : Nmd. 2001 April; 11(3): 269-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11297942&dopt=Abstract

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Immune responses to dystropin: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Ferrer A, Wells KE, Wells DJ. Source: Gene Therapy. 2000 September; 7(17): 1439-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001363&dopt=Abstract

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Immunohistochemical staining of dystrophin on formalin-fixed paraffin-embedded sections in Duchenne/Becker muscular dystrophy and manifesting carriers of Duchenne muscular dystrophy. Author(s): Hoshino S, Ohkoshi N, Watanabe M, Shoji S. Source: Neuromuscular Disorders : Nmd. 2000 August; 10(6): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899449&dopt=Abstract

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Immunological hurdles in the path to gene therapy for Duchenne muscular dystrophy. Author(s): Wells DJ, Ferrer A, Wells KE. Source: Expert Reviews in Molecular Medicine [electronic Resource]. 2002 November 4; 2002: 1-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14585159&dopt=Abstract

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Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Author(s): Simonds AK, Muntoni F, Heather S, Fielding S. Source: Thorax. 1998 November; 53(11): 949-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193393&dopt=Abstract

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Impairment of cardiac autonomic function in patients with Duchenne muscular dystrophy: relationship to myocardial and respiratory function. Author(s): Lanza GA, Dello Russo A, Giglio V, De Luca L, Messano L, Santini C, Ricci E, Damiani A, Fumagalli G, De Martino G, Mangiola F, Bellocci F. Source: American Heart Journal. 2001 May; 141(5): 808-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11320370&dopt=Abstract

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In situ measurements of muscle fiber conduction velocity in Duchenne muscular dystrophy. Author(s): Al-Ani FS, Hamdan FB, Shaikhly KI. Source: Saudi Med J. 2001 March; 22(3): 259-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307114&dopt=Abstract

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In utero fetal muscle biopsy in the diagnosis of Duchenne muscular dystrophy. Author(s): Ladwig D, Mowat D, Tobias V, Taylor PJ, Buckley MF, McNally G, Challis D. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 February; 42(1): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926646&dopt=Abstract

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In utero fetal muscle biopsy: a precious aid for the prenatal diagnosis of Duchenne muscular dystrophy. Author(s): Heckel S, Favre R, Flori J, Koenig M, Mandel J, Gasser B, Chaigne D. Source: Fetal Diagnosis and Therapy. 1999 May-June; 14(3): 127-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364661&dopt=Abstract

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Incidence of cerebral infarction in Duchenne muscular dystrophy. Author(s): Hanajima R, Kawai M. Source: Muscle & Nerve. 1996 July; 19(7): 928. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965857&dopt=Abstract

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Increase in fetal breech presentation in female carriers of Duchenne muscular dystrophy. Author(s): Geifman-Holtzman O, Bernstein IM, Capeless EL, Hawley P, Specht LA, Bianchi DW. Source: American Journal of Medical Genetics. 1997 December 19; 73(3): 276-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415684&dopt=Abstract

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Increased acetylcholine sensitivity in Duchenne muscular dystrophy myotubes. Author(s): Meola G, Mancinelli E, Geremia L, Scarlato G. Source: Italian Journal of Neurological Sciences. 1991 April; 12(2): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2071364&dopt=Abstract

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Increased cerebral choline-compounds in Duchenne muscular dystrophy. Author(s): Kato T, Nishina M, Matsushita K, Hori E, Akaboshi S, Takashima S. Source: Neuroreport. 1997 April 14; 8(6): 1435-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172149&dopt=Abstract

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Increased expression of IGF-binding protein-5 in Duchenne muscular dystrophy (DMD) fibroblasts correlates with the fibroblast-induced downregulation of DMD myoblast growth: an in vitro analysis. Author(s): Melone MA, Peluso G, Galderisi U, Petillo O, Cotrufo R. Source: Journal of Cellular Physiology. 2000 October; 185(1): 143-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942528&dopt=Abstract

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Increased number of caveolae and caveolin-3 overexpression in Duchenne muscular dystrophy. Author(s): Repetto S, Bado M, Broda P, Lucania G, Masetti E, Sotgia F, Carbone I, Pavan A, Bonilla E, Cordone G, Lisanti MP, Minetti C. Source: Biochemical and Biophysical Research Communications. 1999 August 11; 261(3): 547-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10441463&dopt=Abstract

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Indicators of need for mechanical ventilation in Duchenne muscular dystrophy and spinal muscular atrophy. Author(s): Lyager S, Steffensen B, Juhl B. Source: Chest. 1995 September; 108(3): 779-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7656633&dopt=Abstract

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Inspiratory flow reserve in boys with Duchenne muscular dystrophy. Author(s): De Bruin PF, Ueki J, Bush A, Y Manzur A, Watson A, Pride NB. Source: Pediatric Pulmonology. 2001 June; 31(6): 451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389578&dopt=Abstract

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Intelligence and Duchenne muscular dystrophy: full-scale, verbal, and performance intelligence quotients. Author(s): Cotton S, Voudouris NJ, Greenwood KM. Source: Developmental Medicine and Child Neurology. 2001 July; 43(7): 497-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463183&dopt=Abstract

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Is glutamine a 'conditionally essential' amino acid in Duchenne muscular dystrophy? Author(s): Hankard R, Mauras N, Hammond D, Haymond M, Darmaun D. Source: Clinical Nutrition (Edinburgh, Lothian). 1999 December; 18(6): 365-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10634922&dopt=Abstract

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Knee moments in Duchenne muscular dystrophy. Author(s): Siegel IM. Source: Lancet. 1986 October 25; 2(8513): 977-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2877155&dopt=Abstract

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Knee moments in Duchenne muscular dystrophy. Author(s): Khodadadeh S, McClelland MR, Patrick JH, Edwards RH, Evans GA. Source: Lancet. 1986 September 6; 2(8506): 544-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2875283&dopt=Abstract

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Learning and transfer in two perceptual-motor skills in Duchenne muscular dystrophy. Author(s): Nakafuji A, Tsuji K. Source: Percept Mot Skills. 2001 October; 93(2): 339-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11769887&dopt=Abstract

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Lightweight, modular knee-ankle-foot orthosis for Duchenne muscular dystrophy: design, development, and evaluation. Author(s): Taktak DM, Bowker P. Source: Archives of Physical Medicine and Rehabilitation. 1995 December; 76(12): 115662. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8540794&dopt=Abstract

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Localisation and characterisation of dystrophin in the central nervous system of controls and patients with Duchenne muscular dystrophy. Author(s): Uchino M, Teramoto H, Naoe H, Yoshioka K, Miike T, Ando M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 1994 April; 57(4): 426-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8163990&dopt=Abstract

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Longitudinal data analysis: an application to construction of a natural history profile of Duchenne muscular dystrophy. Author(s): Hyde SA, Steffensen BF, Floytrup I, Glent S, Kroksmark AK, Salling B, Werlauff U, Erlandsen M. Source: Neuromuscular Disorders : Nmd. 2001 March; 11(2): 165-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257473&dopt=Abstract

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Longitudinal study of spinal deformity in Duchenne muscular dystrophy. Author(s): Oda T, Shimizu N, Yonenobu K, Ono K, Nabeshima T, Kyoh S. Source: Journal of Pediatric Orthopedics. 1993 July-August; 13(4): 478-88. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8370781&dopt=Abstract

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Long-term follow-up of patients with Duchenne muscular dystrophy receiving ventilatory support. Author(s): Fukunaga H, Okubo R, Moritoyo T, Kawashima N, Osame M. Source: Muscle & Nerve. 1993 May; 16(5): 554-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8515763&dopt=Abstract

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Long-term persistence of donor nuclei in a Duchenne muscular dystrophy patient receiving bone marrow transplantation. Author(s): Gussoni E, Bennett RR, Muskiewicz KR, Meyerrose T, Nolta JA, Gilgoff I, Stein J, Chan YM, Lidov HG, Bonnemann CG, Von Moers A, Morris GE, Den Dunnen JT, Chamberlain JS, Kunkel LM, Weinberg K. Source: The Journal of Clinical Investigation. 2002 September; 110(6): 807-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12235112&dopt=Abstract

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Long-term results of spine surgery in Duchenne muscular dystrophy. Author(s): Granata C, Merlini L, Cervellati S, Ballestrazzi A, Giannini S, Corbascio M, Lari S. Source: Neuromuscular Disorders : Nmd. 1996 January; 6(1): 61-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8845720&dopt=Abstract

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Long-term ventilation for patients with Duchenne muscular dystrophy : physicians' beliefs and practices. Author(s): Gibson B. Source: Chest. 2001 March; 119(3): 940-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11243978&dopt=Abstract

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Looking under every rock: Duchenne muscular dystrophy and traditional Chinese medicine. Author(s): Urtizberea JA, Fan QS, Vroom E, Recan D, Kaplan JC. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561492&dopt=Abstract

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Loss of a single amino acid from dystrophin resulting in Duchenne muscular dystrophy with retention of dystrophin protein. Author(s): Becker K, Robb SA, Hatton Z, Yau SC, Abbs S, Roberts RG. Source: Human Mutation. 2003 June; 21(6): 651. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14961551&dopt=Abstract

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Lower limb surgery in Duchenne muscular dystrophy. Author(s): Forst J, Forst R. Source: Neuromuscular Disorders : Nmd. 1999 May; 9(3): 176-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382913&dopt=Abstract

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Lung clearance in children with Duchenne muscular dystrophy or spinal muscular atrophy with and without CPAP (continuous positive airway pressure). Author(s): Klefbeck B, Svartengren K, Camner P, Philipson K, Svartengren M, Sejersen T, Mattsson E. Source: Experimental Lung Research. 2001 September; 27(6): 469-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11558965&dopt=Abstract

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Lung function in Duchenne muscular dystrophy. Author(s): Galasko CS, Williamson JB, Delaney CM. Source: European Spine Journal : Official Publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society. 1995; 4(5): 263-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8581525&dopt=Abstract

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Macroemg in manifesting carriers of Duchenne muscular dystrophy. Author(s): Szmidt-Salkowska E, Rowinska-Marcinska K, Fidzianska A, HausmanowaPetrusewicz I. Source: Electromyogr Clin Neurophysiol. 1999 March; 39(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10207677&dopt=Abstract

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Mivacurium administration in children with Duchenne muscular dystrophy. Author(s): Tobias JD, Uslu M. Source: Anesthesia and Analgesia. 2000 February; 90(2): 498-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10648347&dopt=Abstract

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Mode of death in Duchenne muscular dystrophy. Author(s): Patterson V, Morrison O, Hicks E. Source: Lancet. 1991 March 30; 337(8744): 801-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1672433&dopt=Abstract

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Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Author(s): Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, Harper HA, Robinson AS, Engelhardt JF, Brooks SV, Chamberlain JS. Source: Nature Medicine. 2002 March; 8(3): 253-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11875496&dopt=Abstract

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Mononuclear cell analysis of muscle biopsies in prednisone-treated and untreated Duchenne muscular dystrophy. CIDD Study Group. Author(s): Kissel JT, Burrow KL, Rammohan KW, Mendell JR. Source: Neurology. 1991 May; 41(5): 667-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2027481&dopt=Abstract

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Multiple regulatory events controlling the expression and localization of utrophin in skeletal muscle fibers: insights into a therapeutic strategy for Duchenne muscular dystrophy. Author(s): Jasmin BJ, Angus LM, Belanger G, Chakkalakal JV, Gramolini AO, Lunde JA, Stocksley MA, Thompson J. Source: Journal of Physiology, Paris. 2002 January-March; 96(1-2): 31-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755781&dopt=Abstract

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Multiplex PCR excludes Duchenne muscular dystrophy in a twin pregnancy. Author(s): Wadelius C, Anneran G, Dahl N, Holmgren G, Gustavson KH. Source: Clinical Genetics. 1991 April; 39(4): 314-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2070552&dopt=Abstract

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Muscle and joint elastic properties during elbow flexion in Duchenne muscular dystrophy. Author(s): Cornu C, Goubel F, Fardeau M. Source: The Journal of Physiology. 2001 June 1; 533(Pt 2): 605-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389216&dopt=Abstract

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Myoblast transfer therapy for Duchenne muscular dystrophy. Author(s): Law PK, Goodwin TG, Fang QW, Chen M, Li HJ, Florendo JA, Kirby DS. Source: Acta Paediatr Jpn. 1991 April; 33(2): 206-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1957647&dopt=Abstract

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Myocardial cell damage in Duchenne muscular dystrophy. Author(s): Ramaciotti C, Iannaccone ST, Scott WA. Source: Pediatric Cardiology. 2003 September-October; 24(5): 503-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14627325&dopt=Abstract

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Neonatal screening for Duchenne muscular dystrophy: a novel semiquantitative application of the bioluminescence test for creatine kinase in a pilot national program in Cyprus. Author(s): Drousiotou A, Ioannou P, Georgiou T, Mavrikiou E, Christopoulos G, Kyriakides T, Voyasianos M, Argyriou A, Middleton L. Source: Genetic Testing. 1998; 2(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464597&dopt=Abstract

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New aspects of calcium signaling in skeletal muscle cells: implications in Duchenne muscular dystrophy. Author(s): Gailly P. Source: Biochimica Et Biophysica Acta. 2002 November 4; 1600(1-2): 38-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12445457&dopt=Abstract

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Newborn screening for Duchenne muscular dystrophy. Author(s): Parsons EP, Bradley DM, Clarke AJ. Source: Archives of Disease in Childhood. 2003 January; 88(1): 91-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495984&dopt=Abstract

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Newborn screening for Duchenne muscular dystrophy: a psychosocial study. Author(s): Parsons EP, Clarke AJ, Hood K, Lycett E, Bradley DM. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 2002 March; 86(2): F91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882550&dopt=Abstract

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Newly recognized exons induced by a splicing abnormality from an intronic mutation of the dystrophin gene resulting in Duchenne muscular dystrophy. Mutations in brief no. 213. Online. Author(s): Ikezawa M, Nishino I, Goto Y, Miike T, Nonaka I. Source: Human Mutation. 1999; 13(2): 170. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10094556&dopt=Abstract

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NO vascular control in Duchenne muscular dystrophy. Author(s): Crosbie RH. Source: Nature Medicine. 2001 January; 7(1): 27-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11135610&dopt=Abstract

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Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy. Author(s): Ishikawa Y, Bach JR. Source: American Journal of Respiratory and Critical Care Medicine. 2000 February; 161(2 Pt 1): 675-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10673215&dopt=Abstract

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Nocturnal oxygenation and prognosis in Duchenne muscular dystrophy. Author(s): Phillips MF, Smith PE, Carroll N, Edwards RH, Calverley PM. Source: American Journal of Respiratory and Critical Care Medicine. 1999 July; 160(1): 198-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10390400&dopt=Abstract

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Novel deletion at the M and P promoters of the human dystrophin gene associated with a Duchenne muscular dystrophy. Author(s): Frisso G, Sampaolo S, Pastore L, Carlomagno A, Calise RM, Di Iorio G, Salvatore F. Source: Neuromuscular Disorders : Nmd. 2002 June; 12(5): 494-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031623&dopt=Abstract

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Novel therapies for Duchenne muscular dystrophy. Author(s): Kapsa R, Kornberg AJ, Byrne E. Source: Lancet. Neurology. 2003 May; 2(5): 299-310. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849184&dopt=Abstract

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Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy. Author(s): Mostacciuolo ML, Miorin M, Vitiello L, Rampazzo A, Fanin M, Angelini C, Danieli GA. Source: American Journal of Medical Genetics. 1994 March 1; 50(1): 84-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8160758&dopt=Abstract

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Octreotide enhances positive calcium balance in Duchenne muscular dystrophy. Author(s): Nutting DF, Schriock EA, Palmieri GM, Bittle JB, Elmendorf BJ, Horner LH, Edwards MC, Griffin JW, Sacks HS, Bertorini TE. Source: The American Journal of the Medical Sciences. 1995 September; 310(3): 91-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7668311&dopt=Abstract

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Oligonucleotides against a splicing enhancer sequence led to dystrophin production in muscle cells from a Duchenne muscular dystrophy patient. Author(s): Takeshima Y, Wada H, Yagi M, Ishikawa Y, Ishikawa Y, Minami R, Nakamura H, Matsuo M. Source: Brain & Development. 2001 December; 23(8): 788-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720794&dopt=Abstract

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On the origin of deletions and point mutations in Duchenne muscular dystrophy: most deletions arise in oogenesis and most point mutations result from events in spermatogenesis. Author(s): Grimm T, Meng G, Liechti-Gallati S, Bettecken T, Muller CR, Muller B. Source: Journal of Medical Genetics. 1994 March; 31(3): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8014964&dopt=Abstract

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One base deletion in the cysteine-rich domain of the dystrophin gene in Duchenne muscular dystrophy patients. Author(s): Tsukamoto H, Inui K, Matsuoka T, Yanagihara I, Fukushima H, Okada S. Source: Human Molecular Genetics. 1994 June; 3(6): 995-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7951251&dopt=Abstract

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Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Author(s): Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W. Source: Neurological Research. 2000 March; 22(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763500&dopt=Abstract

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Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy. Author(s): Hankard RG, Hammond D, Haymond MW, Darmaun D. Source: Pediatric Research. 1998 February; 43(2): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9475288&dopt=Abstract

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Origins and early descriptions of “Duchenne muscular dystrophy”. Author(s): Tyler KL. Source: Muscle & Nerve. 2003 October; 28(4): 402-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14506712&dopt=Abstract

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Orthopedic approaches for the treatment of lower extremity contractures in the Duchenne muscular dystrophy patient in the United States and Canada. Author(s): Hsu JD. Source: Seminars in Neurology. 1995 March; 15(1): 6-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7638460&dopt=Abstract

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Oxidative damage to muscle protein in Duchenne muscular dystrophy. Author(s): Haycock JW, MacNeil S, Jones P, Harris JB, Mantle D. Source: Neuroreport. 1996 December 20; 8(1): 357-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9051810&dopt=Abstract

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Parental stress in mothers of boys with duchenne muscular dystrophy. Author(s): Nereo NE, Fee RJ, Hinton VJ. Source: Journal of Pediatric Psychology. 2003 October-November; 28(7): 473-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12968039&dopt=Abstract

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Pelvic or lumbar fixation for the surgical management of scoliosis in duchenne muscular dystrophy. Author(s): Sengupta DK, Mehdian SH, McConnell JR, Eisenstein SM, Webb JK. Source: Spine. 2002 September 15; 27(18): 2072-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634572&dopt=Abstract

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Physical capacity in non-ambulatory people with Duchenne muscular dystrophy or spinal muscular atrophy: a longitudinal study. Author(s): Steffensen BF, Lyager S, Werge B, Rahbek J, Mattsson E. Source: Developmental Medicine and Child Neurology. 2002 September; 44(9): 623-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12227617&dopt=Abstract

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Postoperative malnutrition in Duchenne muscular dystrophy. Author(s): Iannaccone ST, Owens H, Scott J, Teitell B. Source: Journal of Child Neurology. 2003 January; 18(1): 17-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661933&dopt=Abstract

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Predictive factors of cessation of ambulation in patients with Duchenne muscular dystrophy. Author(s): Bakker JP, De Groot IJ, Beelen A, Lankhorst GJ. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 2002 December; 81(12): 906-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12447089&dopt=Abstract

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Prednisolone in Duchenne muscular dystrophy. Author(s): Rahman MM, Hannan MA, Mondol BA, Bhoumick NB, Haque A. Source: Bangladesh Med Res Counc Bull. 2001 April; 27(1): 38-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692899&dopt=Abstract

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Prenatal deletion detection in a sporadic case of Duchenne muscular dystrophy without genotype information from the affected individual. Author(s): Peinemann F, Wagner M, Franke U, Kulle M, Reiss J. Source: European Journal of Pediatrics. 1991 February; 150(4): 256-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1851486&dopt=Abstract

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Prognostic value of electrocardiograms, ventricular late potentials, ventricular arrhythmias, and left ventricular systolic dysfunction in patients with Duchenne muscular dystrophy. Author(s): Corrado G, Lissoni A, Beretta S, Terenghi L, Tadeo G, Foglia-Manzillo G, Tagliagambe LM, Spata M, Santarone M. Source: The American Journal of Cardiology. 2002 April 1; 89(7): 838-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11909570&dopt=Abstract

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Progress in gene therapy for Duchenne muscular dystrophy. Author(s): Clemens PR, Duncan FJ. Source: Curr Neurol Neurosci Rep. 2001 January; 1(1): 89-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898504&dopt=Abstract

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Progress toward gene therapy of Duchenne muscular dystrophy. Author(s): Hartigan-O'Connor D, Chamberlain JS. Source: Seminars in Neurology. 1999; 19(3): 323-32. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194388&dopt=Abstract

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Quadriceps femoris muscle assist orthosis in Duchenne muscular dystrophy. Author(s): Siegel IM, Silverman O, Silverman M. Source: Physical Therapy. 1982 September; 62(9): 1296. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7111403&dopt=Abstract

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Quantitation of muscle function in children: a prospective study in Duchenne muscular dystrophy. Author(s): Scott OM, Hyde SA, Goddard C, Dubowitz V. Source: Muscle & Nerve. 1982 April; 5(4): 291-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7099196&dopt=Abstract

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Quantitative analysis of quadriceps muscle biopsy. Results in 7 definite and 45 possible carriers of Duchenne muscular dystrophy. Author(s): Doriguzzi C, Palmucci L, Mongini T, Leone M, Gagnor E, Gagliano A, Schiffer D. Source: Journal of the Neurological Sciences. 1986 February; 72(2-3): 201-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3711934&dopt=Abstract

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Quantitative assessment of calf circumference in Duchenne muscular dystrophy patients. Author(s): Beenakker EA, de Vries J, Fock JM, van Tol M, Brouwer OF, Maurits NM, van der Hoeven JH. Source: Neuromuscular Disorders : Nmd. 2002 October; 12(7-8): 639-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12207931&dopt=Abstract

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Quantitative ELISA for platelet m-calpain: a phenotypic index for detection of carriers of Duchenne muscular dystrophy. Author(s): Hussain T, Kumar DV, Sundaram C, Mohandas S, Anandaraj MP. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 January 12; 269(1): 13-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9498100&dopt=Abstract

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Quantitative MR evaluation of body composition in patients with Duchenne muscular dystrophy. Author(s): Pichiecchio A, Uggetti C, Egitto MG, Berardinelli A, Orcesi S, Gorni KO, Zanardi C, Tagliabue A. Source: European Radiology. 2002 November; 12(11): 2704-9. Epub 2002 May 08. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12386760&dopt=Abstract

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Quantitative MR relaxometry study of muscle composition and function in Duchenne muscular dystrophy. Author(s): Huang Y, Majumdar S, Genant HK, Chan WP, Sharma KR, Yu P, Mynhier M, Miller RG. Source: Journal of Magnetic Resonance Imaging : Jmri. 1994 January-February; 4(1): 5964. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8148557&dopt=Abstract

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Reading ability and processing in Duchenne muscular dystrophy and spinal muscular atrophy. Author(s): Billard C, Gillet P, Barthez M, Hommet C, Bertrand P. Source: Developmental Medicine and Child Neurology. 1998 January; 40(1): 12-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9459212&dopt=Abstract

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Reduced aquaporin 4 expression in the muscle plasma membrane of patients with Duchenne muscular dystrophy. Author(s): Wakayama Y, Jimi T, Inoue M, Kojima H, Murahashi M, Kumagai T, Yamashita S, Hara H, Shibuya S. Source: Archives of Neurology. 2002 March; 59(3): 431-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11890849&dopt=Abstract

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Relating familial stress to the psychosocial adjustment of adolescents with Duchenne muscular dystrophy. Author(s): Reid DT, Renwick RM. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 2001 June; 24(2): 83-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421396&dopt=Abstract

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Relationship between utrophin and regenerating muscle fibers in duchenne muscular dystrophy. Author(s): Shim JY, Kim TS. Source: Yonsei Medical Journal. 2003 February; 44(1): 15-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12619170&dopt=Abstract

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Remission of clinical signs in early duchenne muscular dystrophy on intermittent low-dosage prednisolone therapy. Author(s): Dubowitz V, Kinali M, Main M, Mercuri E, Muntoni F. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2002; 6(3): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363102&dopt=Abstract

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Respiratory concerns in Duchenne muscular dystrophy (DMD). Author(s): Leger P, Leger SS. Source: Pediatr Pulmonol Suppl. 1997; 16: 137-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9443242&dopt=Abstract

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Resting energy expenditure and energy substrate utilization in children with Duchenne muscular dystrophy. Author(s): Hankard R, Gottrand F, Turck D, Carpentier A, Romon M, Farriaux JP. Source: Pediatric Research. 1996 July; 40(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8798242&dopt=Abstract

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Retroviral vectors for gene therapy of Duchenne muscular dystrophy. Author(s): Fassati A, Bresolin N. Source: Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2000; 21(5 Suppl): S925-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11382191&dopt=Abstract

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Revertant fibres: a possible genetic therapy for Duchenne muscular dystrophy? Author(s): Wilton SD, Dye DE, Blechynden LM, Laing NG. Source: Neuromuscular Disorders : Nmd. 1997 July; 7(5): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9267847&dopt=Abstract

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Row-a-boat phenomenon: respiratory compensation in advanced Duchenne muscular dystrophy. Author(s): Yasuma F, Kato T, Matsuoka Y, Konagaya M. Source: Chest. 2001 June; 119(6): 1836-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11399712&dopt=Abstract

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Screening of gene deletions by polymerase chain reaction in Japanese patients with Duchenne muscular dystrophy. Author(s): Nakajima T, Matsuo M, Kitoh Y, Takumi T, Nishio H, Masumura T, Koga J, Nakamura H. Source: Journal of Neurology. 1991 February; 238(1): 6-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2030378&dopt=Abstract

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Short stature in Duchenne muscular dystrophy. Author(s): Rapaport D, Colletto GM, Vainzof M, Duaik MC, Zatz M. Source: Growth Regul. 1991 March; 1(1): 11-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1842555&dopt=Abstract

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Skeletal muscle metabolism in Duchenne muscular dystrophy (DMD): an in-vitro proton NMR spectroscopy study. Author(s): Sharma U, Atri S, Sharma MC, Sarkar C, Jagannathan NR. Source: Magnetic Resonance Imaging. 2003 February; 21(2): 145-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12670601&dopt=Abstract

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Special Centennial Workshop-- 101st ENMC International Workshop: Therapeutic Possibilities in Duchenne Muscular Dystrophy, 30th November-2nd December 2001, Naarden, The Netherlands. Author(s): Dubowitz V. Source: Neuromuscular Disorders : Nmd. 2002 May; 12(4): 421-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062262&dopt=Abstract

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S-protein is expressed in necrotic fibers in Duchenne muscular dystrophy and polymyositis. Author(s): Louboutin JP, Navenot JM, Rouger K, Blanchard D. Source: Muscle & Nerve. 2003 May; 27(5): 575-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707977&dopt=Abstract

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ST-segment displacement in Duchenne muscular dystrophy: myocardial necrosis or apoptosis? Author(s): Politano L, Palladino A, Petretta VR, Mansi L, Passamano L, Nigro G, Comi LI, Nigro G. Source: Acta Myol. 2003 May; 22(1): 5-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=13677325&dopt=Abstract

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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Wright JG. Source: Journal of Pediatric Orthopedics. 2003 July-August; 23(4): 564-5; Author Reply 565. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12826961&dopt=Abstract

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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Wright JG. Source: Journal of Pediatric Orthopedics. 2003 May-June; 23(3): 419. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724613&dopt=Abstract

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Surgical prevention of foot deformity in patients with Duchenne muscular dystrophy. Author(s): Scher DM, Mubarak SJ. Source: Journal of Pediatric Orthopedics. 2002 May-June; 22(3): 384-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11961461&dopt=Abstract

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Survival in Duchenne muscular dystrophy: improvements in life expectancy since 1967 and the impact of home nocturnal ventilation. Author(s): Eagle M, Baudouin SV, Chandler C, Giddings DR, Bullock R, Bushby K. Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 926-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467747&dopt=Abstract

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The Duchenne muscular dystrophy population in Denmark, 1977-2001: prevalence, incidence and survival in relation to the introduction of ventilator use. Author(s): Jeppesen J, Green A, Steffensen BF, Rahbek J. Source: Neuromuscular Disorders : Nmd. 2003 December; 13(10): 804-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14678803&dopt=Abstract

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The future of Duchenne muscular dystrophy gene therapy: shrinking the dystrophin gene. Author(s): Roberts M, Dickson G. Source: Curr Opin Mol Ther. 2002 August; 4(4): 343-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222872&dopt=Abstract

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The Golden Freeway: a preliminary evaluation of a pilot study advancing information technology as a social intervention for boys with Duchenne muscular dystrophy and their families. Author(s): Soutter J, Hamilton N, Russell P, Russell C, Bushby K, Sloper P, Bartlett K. Source: Health & Social Care in the Community. 2004 January; 12(1): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14675362&dopt=Abstract

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The mechanism of cerebral evoked potentials by repetitive magnetic stimulation of gastrocnemius muscle in Duchenne muscular dystrophy. Author(s): Guan Y, Cui L, Tang X, Li B, Du H. Source: Chinese Medical Sciences Journal = Chung-Kuo I Hsueh K'o Hsueh Tsa Chih / Chinese Academy of Medical Sciences. 2001 June; 16(2): 115-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901502&dopt=Abstract

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The role of utrophin in the potential therapy of Duchenne muscular dystrophy. Author(s): Perkins KJ, Davies KE. Source: Neuromuscular Disorders : Nmd. 2002 October; 12 Suppl 1: S78-89. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12206801&dopt=Abstract

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The value of deletion analysis for carrier detection in Duchenne muscular dystrophy (DMD). Author(s): Bejjani B, Finn P, Milunsky A, Amos J. Source: Clinical Genetics. 1991 April; 39(4): 245-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2070545&dopt=Abstract

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Three wishes and psychological functioning in boys with duchenne muscular dystrophy. Author(s): Nereo NE, Hinton VJ. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 2003 April; 24(2): 96103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12692454&dopt=Abstract

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Time dependent changes of variables associated with malocclusion in patients with Duchenne muscular dystrophy. Author(s): Matsumoto S, Morinushi T, Ogura T. Source: J Clin Pediatr Dent. 2002 Fall; 27(1): 53-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413173&dopt=Abstract

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Tracheobronchomalacia and tracheal hemorrhage in patients with Duchenne muscular dystrophy receiving long-term ventilation with uncuffed tracheostomies. Author(s): Baydur A, Kanel G. Source: Chest. 2003 April; 123(4): 1307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684330&dopt=Abstract

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Tracheocoele in a Duchenne muscular dystrophy patient. Case report. Author(s): Piazza C, Bolzoni A, Cavaliere S, Peretti G. Source: Acta Otorhinolaryngol Ital. 2003 June; 23(3): 194-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14677314&dopt=Abstract

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Ultrasound tissue characterization detects preclinical myocardial structural changes in children affected by Duchenne muscular dystrophy. Author(s): Giglio V, Pasceri V, Messano L, Mangiola F, Pasquini L, Dello Russo A, Damiani A, Mirabella M, Galluzzi G, Tonali P, Ricci E. Source: Journal of the American College of Cardiology. 2003 July 16; 42(2): 309-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12875769&dopt=Abstract

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Uniparental disomy of the entire X chromosome in a female with Duchenne muscular dystrophy. Author(s): Quan F, Janas J, Toth-Fejel S, Johnson DB, Wolford JK, Popovich BW. Source: American Journal of Human Genetics. 1997 January; 60(1): 160-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8981959&dopt=Abstract

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Update on Duchenne muscular dystrophy. Author(s): Siegel IM. Source: Compr Ther. 1989 March; 15(3): 45-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2650976&dopt=Abstract

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Upper extremity functional assessment scales in children with Duchenne muscular dystrophy: a comparison. Author(s): Hiller LB, Wade CK. Source: Archives of Physical Medicine and Rehabilitation. 1992 June; 73(6): 527-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1622300&dopt=Abstract

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Upregulation of utrophin in the myocardium of a carrier of Duchenne muscular dystrophy. Author(s): Behr TM, Fischer P, Mudra H, Theisen K, Spes C, Uberfuhr P, Muller-Felber W, Pongratz DE, Angermann C. Source: European Heart Journal. 1997 April; 18(4): 699-700. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9129907&dopt=Abstract

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Urinary dysfunction in Duchenne muscular dystrophy. Author(s): Caress JB, Kothari MJ, Bauer SB, Shefner JM. Source: Muscle & Nerve. 1996 July; 19(7): 819-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8965833&dopt=Abstract

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Urinary excretion of acid-soluble peptides in children with Duchenne muscular dystrophy. Author(s): Hirano K, Sakamoto Y. Source: Acta Paediatr Jpn. 1994 December; 36(6): 627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7871971&dopt=Abstract

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Use of DNA probes in detecting carriers of Duchenne muscular dystrophy: selected case studies. Author(s): Prior TW, Blasco PA, Dove JL, Leshner RT, Gruemer HD. Source: Clinical Chemistry. 1989 April; 35(4): 679-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2564818&dopt=Abstract

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Use of dystrophin genomic and cDNA probes for solving difficulties in carrier detection and prenatal diagnosis of Duchenne muscular dystrophy. Author(s): Shomrat R, Driks N, Legum C, Shiloh Y. Source: American Journal of Medical Genetics. 1992 February 1; 42(3): 281-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1536162&dopt=Abstract

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Usefulness of test: manual muscle testing, goniometry, and daily activities for differential diagnosis of Duchenne muscular dystrophy, Becker's mild muscular dystrophy and Becker's severe muscular dystrophy. Author(s): Alvarez M, Rodriguez I, Zuniga-Charles MA. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 1998 March; 21(1): 79-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9924669&dopt=Abstract

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Valley sign in duchenne muscular dystrophy: importance in patients with inconspicuous calves. Author(s): Pradhan S. Source: Neurology India. 2002 June; 50(2): 184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12134184&dopt=Abstract

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Value of myofibrillar protein catabolic rate in Duchenne muscular dystrophy. A study after lower limb surgery. Author(s): Forst J, Kruger P, Forst R. Source: Archives of Orthopaedic and Trauma Surgery. 2000; 120(1-2): 38-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653102&dopt=Abstract

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Variable dystrophin expression in different muscles of a Duchenne muscular dystrophy carrier. Author(s): Muntoni F, Mateddu A, Marrosu MG, Cau M, Congiu R, Melis MA, Cao A, Cianchetti C. Source: Clinical Genetics. 1992 July; 42(1): 35-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1355417&dopt=Abstract

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Variations of gait parameters in Duchenne muscular dystrophy. Author(s): Khodadadeh S, McClelland MR, Patrick JH. Source: Proceedings of the Institution of Mechanical Engineers. Part H, Journal of Engineering in Medicine. 1990; 204(4): 241-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2090127&dopt=Abstract

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Ventilation and breathing pattern during sleep in Duchenne muscular dystrophy. Author(s): Smith PE, Edwards RH, Calverley PM. Source: Chest. 1989 December; 96(6): 1346-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2582842&dopt=Abstract

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Ventilator dependency: decision-making, daily functioning and quality of life for patients with Duchenne muscular dystrophy. Author(s): Miller JR, Colbert AP, Osberg JS. Source: Developmental Medicine and Child Neurology. 1990 December; 32(12): 1078-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2286307&dopt=Abstract

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Ventilator management in Duchenne muscular dystrophy and postpoliomyelitis syndrome: twelve years' experience. Author(s): Curran FJ, Colbert AP. Source: Archives of Physical Medicine and Rehabilitation. 1989 March; 70(3): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2647055&dopt=Abstract

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Ventricular arrhythmia in Duchenne muscular dystrophy: prevalence, significance and prognosis. Author(s): Chenard AA, Becane HM, Tertrain F, de Kermadec JM, Weiss YA. Source: Neuromuscular Disorders : Nmd. 1993 May; 3(3): 201-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7691292&dopt=Abstract

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Vertebral compression in Duchenne muscular dystrophy following deflazacort. Author(s): Talim B, Malaguti C, Gnudi S, Politano L, Merlini L. Source: Neuromuscular Disorders : Nmd. 2002 March; 12(3): 294-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11801403&dopt=Abstract

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Vertebral fractures in boys with Duchenne muscular dystrophy. Author(s): Bothwell JE, Gordon KE, Dooley JM, MacSween J, Cummings EA, Salisbury S. Source: Clinical Pediatrics. 2003 May; 42(4): 353-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12800730&dopt=Abstract

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Wheelchair-mounted robot manipulators. Long term use by patients with Duchenne muscular dystrophy. Author(s): Bach JR, Zeelenberg AP, Winter C. Source: American Journal of Physical Medicine & Rehabilitation / Association of Academic Physiatrists. 1990 April; 69(2): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2331340&dopt=Abstract

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X chromosome in Duchenne muscular dystrophy. Author(s): Spowart G, Buckton KE, Skinner R, Emery AE. Source: Lancet. 1982 May 29; 1(8283): 1251. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6123008&dopt=Abstract

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X inactivation and dystrophin studies in a t(X;12) female: evidence for biochemical normalization in Duchenne muscular dystrophy carriers. Author(s): Wenger SL, Steele MW, Hoffman EP, Barmada MA, Wessel HB. Source: American Journal of Medical Genetics. 1992 August 1; 43(6): 1012-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1415326&dopt=Abstract

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Xanthine oxidase inhibitor in Duchenne muscular dystrophy. Author(s): Tamari H, Ohtani Y, Higashi A, Miyoshino S, Matsuda I. Source: Brain & Development. 1982; 4(2): 137-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6896406&dopt=Abstract

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X-chromosome-coded antigens in Duchenne muscular dystrophy. Author(s): Walsh FS. Source: Biochemical Society Transactions. 1984 June; 12(3): 368-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6376203&dopt=Abstract

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X-chromosome-specific polymorphisms in Duchenne muscular dystrophy: clinical applications. Author(s): O'Brien T. Source: Biochemical Society Transactions. 1984 June; 12(3): 371-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6734896&dopt=Abstract

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X-linked dilated cardiomyopathy. Molecular genetic evidence of linkage to the Duchenne muscular dystrophy (dystrophin) gene at the Xp21 locus. Author(s): Towbin JA, Hejtmancik JF, Brink P, Gelb B, Zhu XM, Chamberlain JS, McCabe ER, Swift M. Source: Circulation. 1993 June; 87(6): 1854-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8504498&dopt=Abstract

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X-linked Duchenne muscular dystrophy in an unusual family with manifesting carriers. Author(s): Kaladhar Reddy B, Anandavalli TE, Reddi OS. Source: Human Genetics. 1984; 67(4): 460-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6490012&dopt=Abstract

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X-linked Duchenne muscular dystrophy. Motor functions and prognosis. Author(s): Hinge HH, Hein-Sorensen O, Reske-Nielsen E. Source: Scandinavian Journal of Rehabilitation Medicine. 1989; 21(1): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2711136&dopt=Abstract

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

Finding Nutrition Studies on Duchenne Muscular 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 “Duchenne muscular 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 “Duchenne muscular dystrophy” (or a synonym): •

A double blind cross over trial of theophylline prophylaxis for sleep hypoxaemia in Duchenne muscular dystrophy. Author(s): Department of Paediatrics, Hammersmith Hospital, London, UK. Source: Khan, Y Heckmatt, J Z Neuromuscul-Disord. 1997 March; 7(2): 75-80 0960-8966

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A pilot trial of plasma infusions in Duchenne muscular dystrophy. Author(s): Department of Biochemistry, Monash University, Clayton, Melbourne, Australia. Source: Arthur, H Austin, L Roberts, L J Aust-Paediatr-J. 1988; 24 Suppl 124-30 0004993X

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A tetrodotoxin- and Mn2(+)-insensitive Na+ current in Duchenne muscular dystrophy. Author(s): Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke, Quebec, Canada. Source: Bkaily, G Jasmin, G Tautu, C Prochek, L Yamamoto, T Sculptoreanu, A Peyrow, M Jacques, D Muscle-Nerve. 1990 October; 13(10): 939-48 0148-639X

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Abnormal calcium homeostasis in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Laboratoire de Physiologie Generale, URA CNRS 1869, Universite de Poitiers, France. Source: Imbert, N Cognard, C Duport, G Guillou, C Raymond, G Cell-Calcium. 1995 September; 18(3): 177-86 0143-4160

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Altered secretion of chondroitin sulfate proteoglycan in Duchenne muscular dystrophy cultures. Source: Hutchison, C J Yasin, R J-Neurol-Sci. 1987 June; 79(1-2): 77-81 0022-510X

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Carnitine deficiency, mitochondrial dysfunction and the heart. Identical defect of oxidative phosphorylation in muscle mitochondria in cardiomyopathy due to carnitine loss and in Duchenne muscular dystrophy. Author(s): Department of Biochemistry I, Erasmus University Rotterdam, The Netherlands. Source: Scholte, H R Rodrigues Pereira, R Busch, H F Jennekens, F G Luyt Houwen, I E Vaandrager Verduin, M H Wien-Klin-Wochenschr. 1989 January 6; 101(1): 12-7 00435325

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Changes in cytosolic resting ionized calcium level and in calcium transients during in vitro development of normal and Duchenne muscular dystrophy cultured skeletal muscle measured by laser cytofluorimetry using indo-1. Author(s): Laboratoire de Physiologie Generale, URA CNRS n 290, Universite de Poitiers, France. Source: Rivet Bastide, M Imbert, N Cognard, C Duport, G Rideau, Y Raymond, G CellCalcium. 1993 July; 14(7): 563-71 0143-4160

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Clinical investigation in Duchenne muscular dystrophy: penicillamine and vitamin E. Author(s): Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37212. Source: Fenichel, G M Brooke, M H Griggs, R C Mendell, J R Miller, J P Moxley, R T 3rd Park, J H Provine, M A Florence, J Kaiser, K K et al. Muscle-Nerve. 1988 November; 11(11): 1164-8 0148-639X

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Corticosteroid therapy in Duchenne muscular dystrophy. Author(s): Department of Anatomy & Cell Biology, State University of New York, Health Science Center at Brooklyn 11203. Source: Khan, M A J-Neurol-Sci. 1993 December 1; 120(1): 8-14 0022-510X

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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Division of Child Neurology, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. [email protected] Source: Wong, B L Christopher, C J-Child-Neurol. 2002 March; 17(3): 183-90 0883-0738

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Duchenne muscular dystrophy and concomitant metastatic alveolar rhabdomyosarcoma. Author(s): Division of Pediatric Hematology/Oncology, All Children's Hospital, University of South Florida College of Medicine, St. Petersburg, USA. Source: Rossbach, H C Lacson, A Grana, N H Barbosa, J L J-Pediatr-Hematol-Oncol. 1999 Nov-December; 21(6): 528-30 1077-4114

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Effect of intraperitoneal injection of glucose on glucose oxidation and energy expenditure in the mdx mouse model of duchenne muscular dystrophy. Author(s): Lab. de Neurobiologie des Regulations, C.N.R.S. URA 1860 College de France, 11 Pl. M. Berthelot, F-75231 Paris Cedex 05, France. Source: Mokhtarian, A Even, P C Pflugers-Arch. 1996 July; 432(3): 379-85 0031-6768

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Effect of mazindol on growth hormone levels in patients with Duchenne muscular dystrophy. Author(s): Departamento de Biologia, Universidade de Sao Paulo, Brazil. Source: Zatz, M Rapaport, D Vainzof, M Pavanello, R de C Rocha, J M Betti, R T Otto, P A Am-J-Med-Genet. 1988 December; 31(4): 821-33 0148-7299

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Electrocardiographic findings in mdx mice: a cardiac phenotype of Duchenne muscular dystrophy. Author(s): Cardiovascular Division, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. Source: Chu, V Otero, J M Lopez, O Sullivan, M F Morgan, J P Amende, I Hampton, T G Muscle-Nerve. 2002 October; 26(4): 513-9 0148-639X

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Hypoosmotic shocks induce elevation of resting calcium level in Duchenne muscular dystrophy myotubes contracting in vitro. Author(s): Laboratoire de Physiologie Generale, CNRS 1869, Universite de Poitiers, France. Source: Imbert, N Vandebrouck, C Constantin, B Duport, G Guillou, C Cognard, C Raymond, G Neuromuscul-Disord. 1996 October; 6(5): 351-60 0960-8966

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Identifying and circumventing the defect in Duchenne muscular dystrophy: clinical and biochemical restoration after practical intervention. Author(s): Knightswood Hospital, Glasgow, U.K. Source: Thomson, W H Med-Hypotheses. 1987 October; 24(2): 187-90 0306-9877

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Immunohistochemical staining of dystrophin on formalin-fixed paraffin-embedded sections in Duchenne/Becker muscular dystrophy and manifesting carriers of Duchenne muscular dystrophy. Author(s): Department of Neurology, Institute of Clinical Medicine, University of Tsukuba, 305-8575, Tsukuba City, Japan. Source: Hoshino, S Ohkoshi, N Watanabe, M Shoji, S Neuromuscul-Disord. 2000 August; 10(6): 425-9 0960-8966

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Is glutamine a 'conditionally essential' amino acid in Duchenne muscular dystrophy? Author(s): Nemours Children's Clinic, Jacksonville, Florida, USA. Source: Hankard, R Mauras, N Hammond, D Haymond, M Darmaun, D Clin-Nutr. 1999 December; 18(6): 365-9 0261-5614

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Myoplasmic (Ca2+) in Duchenne muscular dystrophy patients. Source: Lopez, J R Briceno, L E Sanchez, V Horvart, D Acta-Cient-Venez. 1987; 38(4): 503-4 0001-5504

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Octreotide enhances positive calcium balance in Duchenne muscular dystrophy. Author(s): Department of Physiology, College of Medicine, University of Tennessee, Memphis 38163, USA. Source: Nutting, D F Schriock, E A Palmieri, G M Bittle, J B Elmendorf, B J Horner, L H Edwards, M C Griffin, J W Sacks, H S Bertorini, T E Am-J-Med-Sci. 1995 September; 310(3): 91-8 0002-9629

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Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Author(s): Department of Radiology II and Magnetic Resonance, University of Innsbruck, Children's Hospital, LKH Salzburg, Austria. Source: Felber, S Skladal, D Wyss, M Kremser, C Koller, A Sperl, W Neurol-Res. 2000 March; 22(2): 145-50 0161-6412

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Oral glutamine slows down whole body protein breakdown in Duchenne muscular dystrophy. Author(s): Nemours Children's Clinic, Jacksonville, Florida 32247, USA. Source: Hankard, R G Hammond, D Haymond, M W Darmaun, D Pediatr-Res. 1998 February; 43(2): 222-6 0031-3998

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Predictions of energy intake and energy allowance of patients with Duchenne muscular dystrophy and their validity. Author(s): Department of Nutrition, School of Medicine, University of Tokushima, Japan. Source: Okada, K Manabe, S Sakamoto, S Ohnaka, M Niiyama, Y J-Nutr-Sci-Vitaminol(Tokyo). 1992 April; 38(2): 155-61 0301-4800

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Prednisolone in Duchenne muscular dystrophy. Author(s): Deptt. of Neuromedicine, SOMC, Sylhet. Source: Rahman, M M Hannan, M A Mondol, B A Bhoumick, N B Haque, A Bangladesh-Med-Res-Counc-Bull. 2001 April; 27(1): 38-42 0377-9238

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Purine and carnitine metabolism in muscle of patients with Duchenne muscular dystrophy. Author(s): Departamento de Bioquimica, Hospital General de Galicia, Spain. Source: Camina, F Novo Rodriguez, M I Rodriguez Segade, S Castro Gago, M ClinChim-Acta. 1995 December 29; 243(2): 151-64 0009-8981

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Resting energy expenditure and energy substrate utilization in children with Duchenne muscular dystrophy. Author(s): Service de Pediatrie, Gastroenterologie Pediatrique et Genetique Medicale, CHRU Lille, France. Source: Hankard, R Gottrand, F Turck, D Carpentier, A Romon, M Farriaux, J P PediatrRes. 1996 July; 40(1): 29-33 0031-3998

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Selenium and vitamin E treatment of Duchenne muscular dystrophy: no effect on muscle function. Author(s): Department of Neurophysiology, University Hospital, Linkoping, Sweden.

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Source: Backman, E Nylander, E Johansson, I Henriksson, K G Tagesson, C Acta-NeurolScand. 1988 November; 78(5): 429-35 0001-6314 •

Steroids in Duchenne muscular dystrophy--deflazacort trial. Author(s): Seccion de Enfermedades Neuromusculares, Hospital Frances, Buenos Aires, Argentina. Source: Mesa, L E Dubrovsky, A L Corderi, J Marco, P Flores, D Neuromuscul-Disord. 1991; 1(4): 261-6 0960-8966

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The effect of mazindol on growth hormone secretion in boys with Duchenne muscular dystrophy. Author(s): University Department of Medicine, Royal Liverpool Hospital, UK. Source: Coakley, J H Moorcraft, J Hipkin, L J Smith, C S Griffiths, R D Edwards, R H JNeurol-Neurosurg-Psychiatry. 1988 December; 51(12): 1551-7 0022-3050

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Urinary excretion of selenium and other minerals in patients with Duchenne muscular dystrophy (M.D.) and Werdnig-Hoffman (W-H) spinal atrophy. Source: Ahlrot Westerlund, B. Carlmark, B. Nutr-Res. Elmsford, N.Y. : Pergamon Press. 1985. (suppl. 1) page 406-409. ill. 0271-5317

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Wheat kernel ingestion protects from progression of muscle weakness in mdx mice, an animal model of Duchenne muscular dystrophy. Author(s): Department of Neuropediatrics, Virchow Medical Center, Humboldt University, Berlin, Germany. Source: Hubner, C Lehr, H A Bodlaj, R Finckh, B Oexle, K Marklund, S L Freudenberg, K Kontush, A Speer, A Terwolbeck, K Voit, T Kohlschutter, A Pediatr-Res. 1996 September; 40(3): 444-9 0031-3998

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

•

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

•

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

•

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/

•

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

•

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

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

The following is a specific Web list relating to Duchenne muscular dystrophy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

Minerals Creatine Monohydrate Source: Healthnotes, Inc.; www.healthnotes.com

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

2 Years' experience with inspiratory muscle training in patients with neuromuscular disorders. Author(s): Koessler W, Wanke T, Winkler G, Nader A, Toifl K, Kurz H, Zwick H. Source: Chest. 2001 September; 120(3): 765-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11555507&dopt=Abstract

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Activity of creatine kinase in sera from healthy women, carriers of Duchenne muscular dystrophy and cord blood, determined by the “European” recommended method with NAC-EDTA activation. Author(s): Moss DW, Whitaker KB, Parmar C, Heckmatt J, Wikowski J, Sewry C, Dubowitz V.

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Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1981 October 26; 116(2): 209-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6794955&dopt=Abstract •

Actomyosin alterations in Duchenne muscular dystrophy. Author(s): Samaha FJ. Source: Archives of Neurology. 1973 June; 28(6): 405-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4267103&dopt=Abstract

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Administration of chinese herbal medicines facilitates the locomotor activity in dystrophin-deficient mice. Author(s): Chen SS, Wang DC, Chen TJ, Yang SL. Source: The American Journal of Chinese Medicine. 2001; 29(2): 281-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527070&dopt=Abstract

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Ca2+ transport in erythrocytes from patients with Duchenne muscular dystrophy. Author(s): Pijst HL, Scholte HR. Source: Journal of the Neurological Sciences. 1983 August-September; 60(3): 411-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6138395&dopt=Abstract

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Cell transplantation as an experimental treatment for Duchenne muscular dystrophy. Author(s): Law PK, Goodwin TG, Fang Q, Deering MB, Duggirala V, Larkin C, Florendo JA, Kirby DS, Li HJ, Chen M, et al. Source: Cell Transplantation. 1993 November-December; 2(6): 485-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8167934&dopt=Abstract

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Clinical pharmacology of the dietary supplement creatine monohydrate. Author(s): Persky AM, Brazeau GA. Source: Pharmacological Reviews. 2001 June; 53(2): 161-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11356982&dopt=Abstract

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Complement and myoblast transfer therapy: donor myoblast survival is enhanced following depletion of host complement C3 using cobra venom factor, but not in the absence of C5. Author(s): Hodgetts SI, Grounds MD. Source: Immunology and Cell Biology. 2001 June; 79(3): 231-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11380675&dopt=Abstract

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Corticosteroids in Duchenne muscular dystrophy: a reappraisal. Author(s): Wong BL, Christopher C.

Alternative Medicine 83

Source: Journal of Child Neurology. 2002 March; 17(3): 183-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12026233&dopt=Abstract •

Creatine supplementation improves intracellular Ca2+ handling and survival in mdx skeletal muscle cells. Author(s): Pulido SM, Passaquin AC, Leijendekker WJ, Challet C, Wallimann T, Ruegg UT. Source: Febs Letters. 1998 November 20; 439(3): 357-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9845353&dopt=Abstract

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Creatine supplementation reduces skeletal muscle degeneration and enhances mitochondrial function in mdx mice. Author(s): Passaquin AC, Renard M, Kay L, Challet C, Mokhtarian A, Wallimann T, Ruegg UT. Source: Neuromuscular Disorders : Nmd. 2002 February; 12(2): 174-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738360&dopt=Abstract

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Cultural differences in family communication about Duchenne muscular dystrophy. Author(s): Fitzpatrick C, Barry C. Source: Developmental Medicine and Child Neurology. 1990 November; 32(11): 967-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2269406&dopt=Abstract

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Deficiency of a 180-kDa extracellular matrix protein in Fukuyama type congenital muscular dystrophy skeletal muscle. Author(s): Sunada Y, Saito F, Higuchi I, Matsumura K, Shimizu T. Source: Neuromuscular Disorders : Nmd. 2002 February; 12(2): 117-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11738352&dopt=Abstract

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Detection of glucocorticoid-like activity in traditional Chinese medicine used for the treatment of Duchenne muscular dystrophy. Author(s): Courdier-Fruh I, Barman L, Wettstein P, Meier T. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 699-704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561491&dopt=Abstract

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Dose-dependent effect of individualized respiratory muscle training in children with Duchenne muscular dystrophy. Author(s): Topin N, Matecki S, Le Bris S, Rivier F, Echenne B, Prefaut C, Ramonatxo M. Source: Neuromuscular Disorders : Nmd. 2002 August; 12(6): 576-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117483&dopt=Abstract

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Dose-dependent effects of inspiratory muscle training in neuromuscular disorders. Author(s): Winkler G, Zifko U, Nader A, Frank W, Zwick H, Toifl K, Wanke T.

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Source: Muscle & Nerve. 2000 August; 23(8): 1257-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10918264&dopt=Abstract •

Duchenne muscular dystrophy and concomitant metastatic alveolar rhabdomyosarcoma. Author(s): Rossbach HC, Lacson A, Grana NH, Barbosa JL. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 November-December; 21(6): 528-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10598666&dopt=Abstract

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Duchenne muscular dystrophy--parental perceptions. Author(s): Bothwell JE, Dooley JM, Gordon KE, MacAuley A, Camfield PR, MacSween J. Source: Clinical Pediatrics. 2002 March; 41(2): 105-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931326&dopt=Abstract

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Effects of iron deprivation on the pathology and stress protein expression in murine X-linked muscular dystrophy. Author(s): Bornman L, Rossouw H, Gericke GS, Polla BS. Source: Biochemical Pharmacology. 1998 September 15; 56(6): 751-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751080&dopt=Abstract

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Erythrocyte membrane autophosphorylation in Duchenne muscular dystrophy: effect of two methods of erythrocyte ghost preparation on results. Author(s): Roses AD. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1979 July 2; 95(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=509731&dopt=Abstract

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Evidence for the association of dystrophin with the transverse tubular system in skeletal muscle. Author(s): Knudson CM, Hoffman EP, Kahl SD, Kunkel LM, Campbell KP. Source: The Journal of Biological Chemistry. 1988 June 15; 263(17): 8480-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3286650&dopt=Abstract

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Feasibility, safety, and efficacy of myoblast transfer therapy on Duchenne muscular dystrophy boys. Author(s): Law PK, Goodwin TG, Fang Q, Duggirala V, Larkin C, Florendo JA, Kirby DS, Deering MB, Li HJ, Chen M, et al. Source: Cell Transplantation. 1992; 1(2-3): 235-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1344295&dopt=Abstract

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Gene therapy and tissue engineering based on muscle-derived stem cells. Author(s): Deasy BM, Huard J.

Alternative Medicine 85

Source: Curr Opin Mol Ther. 2002 August; 4(4): 382-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222876&dopt=Abstract •

Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species. Author(s): Buetler TM, Renard M, Offord EA, Schneider H, Ruegg UT. Source: The American Journal of Clinical Nutrition. 2002 April; 75(4): 749-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11916763&dopt=Abstract

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Inspiratory muscle training in patients with Duchenne muscular dystrophy. Author(s): Wanke T, Toifl K, Merkle M, Formanek D, Lahrmann H, Zwick H. Source: Chest. 1994 February; 105(2): 475-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8306750&dopt=Abstract

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Intrauterine stem cell therapy. Author(s): Fisk NM, Chan J, O'Donoghue K. Source: Ann Acad Med Singapore. 2003 September; 32(5 Suppl): S8-10. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14968717&dopt=Abstract

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Long-term noninvasive ventilation in children and adolescents with neuromuscular disorders. Author(s): Mellies U, Ragette R, Dohna Schwake C, Boehm H, Voit T, Teschler H. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 2003 October; 22(4): 631-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14582916&dopt=Abstract

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Looking under every rock: Duchenne muscular dystrophy and traditional Chinese medicine. Author(s): Urtizberea JA, Fan QS, Vroom E, Recan D, Kaplan JC. Source: Neuromuscular Disorders : Nmd. 2003 November; 13(9): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14561492&dopt=Abstract

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Maximum insufflation capacity. Author(s): Kang SW, Bach JR. Source: Chest. 2000 July; 118(1): 61-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10893360&dopt=Abstract

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Na+ + K+ ATPase of erythrocyte membranes in Duchenne muscular dystrophy. Author(s): Mawatari S, Igisu H, Kuroiwa Y, Miyoshino S.

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Source: Neurology. 1981 March; 31(3): 293-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6259557&dopt=Abstract •

Neuromuscular reaction to paired stimuli. Author(s): Reitter BF, Johannsen S. Source: Muscle & Nerve. 1982 October; 5(8): 593-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7155172&dopt=Abstract

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Novel therapies for Duchenne muscular dystrophy. Author(s): Kapsa R, Kornberg AJ, Byrne E. Source: Lancet. Neurology. 2003 May; 2(5): 299-310. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849184&dopt=Abstract

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Oral creatine supplementation in Duchenne muscular dystrophy: a clinical and 31P magnetic resonance spectroscopy study. Author(s): Felber S, Skladal D, Wyss M, Kremser C, Koller A, Sperl W. Source: Neurological Research. 2000 March; 22(2): 145-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10763500&dopt=Abstract

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Pulmonary problems in Duchenne muscular dystrophy. Diagnosis, prophylaxis, and treatment. Author(s): Siegel IM. Source: Physical Therapy. 1975 February; 55(2): 160-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1096180&dopt=Abstract

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Pyruvate kinase: diagnostic value in neuromuscular disease. Author(s): Weinstock IM, Behrendt J, Wittshire HE Jr, Keleman J, Louis S. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1977 November 1; 80(3): 415-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=912912&dopt=Abstract

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Relating familial stress to the psychosocial adjustment of adolescents with Duchenne muscular dystrophy. Author(s): Reid DT, Renwick RM. Source: International Journal of Rehabilitation Research. Internationale Zeitschrift Fur Rehabilitationsforschung. Revue Internationale De Recherches De Readaptation. 2001 June; 24(2): 83-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421396&dopt=Abstract

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Report on the muscular dystrophy campaign workshop: exercise in neuromuscular diseases Newcastle, January 2002. Author(s): Eagle M.

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Source: Neuromuscular Disorders : Nmd. 2002 December; 12(10): 975-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12467755&dopt=Abstract •

Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Rodillo E, Noble-Jamieson CM, Aber V, Heckmatt JZ, Muntoni F, Dubowitz V. Source: Archives of Disease in Childhood. 1989 May; 64(5): 736-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2658856&dopt=Abstract

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Respiratory muscle training in Duchenne muscular dystrophy. Author(s): Smith PE, Coakley JH, Edwards RH. Source: Muscle & Nerve. 1988 July; 11(7): 784-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3405245&dopt=Abstract

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Respiratory muscle training in neuromuscular disease: long-term effects on strength and load perception. Author(s): Gozal D, Thiriet P. Source: Medicine and Science in Sports and Exercise. 1999 November; 31(11): 1522-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589852&dopt=Abstract

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Restoration of dystrophin expression in cultured hybrid myotubes. Author(s): Radojevic V, Oppliger C, Gaschen F, Burgunder JM. Source: Neuropathology and Applied Neurobiology. 2002 October; 28(5): 397-409. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12366821&dopt=Abstract

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Routine suxamethonium in children. A regional survey of current usage. Author(s): Robinson AL, Jerwood DC, Stokes MA. Source: Anaesthesia. 1996 September; 51(9): 874-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8882256&dopt=Abstract

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Selenium metabolism and supplementation in patients with muscular dystrophy. Author(s): Jackson MJ, Coakley J, Stokes M, Edwards RH, Oster O. Source: Neurology. 1989 May; 39(5): 655-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2540451&dopt=Abstract

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Spectrin extractability from erythrocyte in Duchenne muscular dystrophies and the effect of proteases on erythrocyte ghosts. Author(s): Tsuchiya Y, Sugita H, Ishiura S, Imahori K. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1981 February 5; 109(3): 285-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6452973&dopt=Abstract

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Spectrin extractability from erythrocytes in Duchenne muscular dystrophy patients and carriers and in other myopathies. Author(s): Gargioni G, Chiaffoni G, Bonadonna G, Corradini P, Lechi C, de Grandis D, Zatti M. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1985 February 15; 145(3): 259-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3987029&dopt=Abstract

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Update on Duchenne muscular dystrophy. Author(s): Siegel IM. Source: Compr Ther. 1989 March; 15(3): 45-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2650976&dopt=Abstract

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/

•

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

•

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/

•

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

•

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

•

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

•

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

The following is a specific Web list relating to Duchenne muscular dystrophy; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Muscular Dystrophy Source: Integrative Medicine Communications; www.drkoop.com

Alternative Medicine 89

•

Herbs and Supplements Allopurinol Source: Healthnotes, Inc.; www.healthnotes.com BCAAs Source: Prima Communications, Inc.www.personalhealthzone.com

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

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CHAPTER 4. DISSERTATIONS ON DUCHENNE MUSCULAR DYSTROPHY Overview In this chapter, we will give you a bibliography on recent dissertations relating to Duchenne muscular dystrophy. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “Duchenne muscular dystrophy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Duchenne muscular dystrophy, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Duchenne Muscular Dystrophy ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to Duchenne muscular dystrophy. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Adenoviral Vectors for Treatment of Duchenne Muscular Dystrophy by HartiganO'Connor, Dennis Joseph; PhD from University of Michigan, 2003, 158 pages http://wwwlib.umi.com/dissertations/fullcit/3079456

•

Duchenne Muscular Dystrophy Genetic and Biochemical Studies of the Female Carriers and Their Families by Hutton, Elaine M. Edwards; AdvDeg from University of Toronto (Canada), 1970 http://wwwlib.umi.com/dissertations/fullcit/NK09148

•

Maximal Isometric Strength on the Kinetic Communicator System for Duchenne Muscular Dystrophy Patients by Xie, Xiaoqing (Steven); DA from Middle Tennessee State University, 2001, 123 pages http://wwwlib.umi.com/dissertations/fullcit/3030580

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•

The Effect of Physostigmine on Language Processes in Boys with Duchenne Muscular Dystrophy (Memory) by Cameron, Thomas Hartley, PhD from The University of North Carolina at Chapel Hill, 1985, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8527184

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Ultrastructure of Muscle in Typical and Atypical Duchenne Muscular Dystrophy: a Comparative Study by Oteruelo, Felix Teodoro; PhD from The University of Western Ontario (Canada), 1972 http://wwwlib.umi.com/dissertations/fullcit/NK12009

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. CLINICAL MUSCULAR DYSTROPHY

TRIALS

AND

DUCHENNE

Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Duchenne muscular dystrophy.

Recent Trials on Duchenne Muscular Dystrophy The following is a list of recent trials dedicated to Duchenne muscular dystrophy.8 Further information on a trial is available at the Web site indicated. •

An open-label pilot study of Coenzyme Q10 in steroid-treated Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the nutritional supplement Coenzyme Q10 when added to steroids as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should be on a stable dose of steroids for at least six months, and will remain on their usual dose throughout the study. They will complete two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Coenzyme Q10. Once Coenzyme Q10 therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Coenzyme Q10 until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below

8

These are listed at www.ClinicalTrials.gov.

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Web Site: http://clinicaltrials.gov/ct/show/NCT00033189 •

KUL0401: An open-label pilot study of Oxatomide in steroid-naive Duchenne muscular dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is currently recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the safety and efficacy of the mast cell stabilizer Oxatomide as a treatment for Duchenne muscular dystrophy (DMD). Boys with DMD who are enrolled in this study will should not have taken steroids to treat DMD for at least twelve months, and should not have taken any nutritional supplements for at least three months. Subjects will complete a two screening visits within a one-week period, and if enrolled will then have their strength tested monthly for three months before beginning therapy with Oxatomide. Once Oxatomide therapy is started, participants will have their strength tested monthly for six months. Following the six month treatment period, participants will be given the option to remain on Oxatomide until the study is completed. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00033813

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Creatine and Glutamine in Steroid-Naive Duchenne Muscular Dystrophy Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is no longer recruiting patients. Sponsor(s): Cooperative International Neuromuscular Research Group Purpose - Excerpt: This study will help to determine the effectiveness of glutamine and creatine as a possible therapy for DMD. Boys with DMD who are enrolled in this trial will be randomly chosen to receive creatine monohydrate or glutamine or an inactive placebo orally for six months. Once a month during the six-month treatment period, the study participants will have their muscle strength evaluated using manual and computerized testing methods. This study will be conducted at several CINRG Centers throughout the U.S., Belgium, Israel and Puerto Rico. This study is supported by the Muscular Dystrophy Association. Phase(s): Phase II; Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016653

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A multicenter randomized placebo-controlled double-blind study to assess efficacy and safety of glutamine and creatine monohydrate in Duchenne muscular dystrophy (DMD) Condition(s): Muscular Dystrophy, Duchenne Study Status: This study is completed.

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Sponsor(s): National Center for Research Resources (NCRR); Children's National Medical Center Purpose - Excerpt: To establish a collaborative group of clinical trial centers, with standardized equipment and protocols, able to conduct both drug and gene therapy trials in DMD. To evaluate the therapeutic effect of glutamine and creatine monohydrate on muscle strength in children with DMD. To validate the use of QMT (quantitative muscle strength testing) and gait analysis in children with DMD as reliable tools to quantify muscle strength, monitor disease progression and assess therapeutic response. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018109 •

Gentamicin Treatment of Muscular Dystrophy Condition(s): Becker muscular dystrophy; Duchenne muscular dystrophy Study Status: This study is completed. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will evaluate the antibiotic gentamicin for treating patients with muscular dystrophy caused by a specific genetic abnormality known as a nonsense mutation. In studies of mice with this type of muscular dystrophy, gentamicin treatment produced positive changes in muscle tissue. Patients with Duchenne or Becker muscular dystrophy caused by nonsense mutations by may be eligible for this 2week study. Before starting treatment, patients will have evaluations of muscle strength and general well being. Two muscle tissue samples will be taken by needle biopsy, under local anesthetic and sedation. Because of potential risks of hearing loss and kidney toxicity associated with gentamicin, patients will also have a hearing test and blood and urine tests for kidney function before starting treatment. (Currently, gentamicin is commonly prescribed for serious infections of the lungs, heart, and digestive and urinary tracts; adverse effects of hearing loss and kidney toxicity can occur with excessively high drug doses.) Patients will be hospitalized during drug treatment. Gentamicin will be given intravenously (through a vein) once a day for 14 days. Blood samples will be collected daily to monitor drug levels and determine dosage adjustments, if necessary. Urine samples will be collected to assess kidney function. Hearing tests will be done on days 7 and 10. On the last day of the study, hearing, kidney function, and muscle strength will be tested and the results compared with pretreatment levels. Blood and muscle samples will also be taken again for pre-treatment comparison. Hearing, blood, urine, and muscle strength tests will be repeated one month after treatment ends for comparison with previous results. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005574

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Phase III Randomized, Double-Blind Study of Prednisone for Duchenne Muscular Dystrophy Condition(s): Duchenne Muscular Dystrophy

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Study Status: This study is completed. Sponsor(s): National Center for Research Resources (NCRR); National Institute of Neurological Disorders and Stroke (NINDS); University of Rochester Purpose - Excerpt: Objectives: I. Characterize the effect of prednisone on muscle protein metabolism in patients with Duchenne muscular dystrophy. II. Determine whether prednisone changes levels of insulin-like growth factor 1, growth hormone, and insulin. III. Characterize the effect of prednisone on muscle morphometry and muscle localization of utrophin. IV. Compare the prednisone response in patients with Duchenne muscular dystrophy to that seen in normal individuals and in patients with facioscapulohumeral dystrophy. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004646

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Duchenne muscular dystrophy” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 6. DYSTROPHY

PATENTS

ON

DUCHENNE

MUSCULAR

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.9 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 “Duchenne muscular dystrophy” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Duchenne muscular dystrophy, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Duchenne Muscular Dystrophy By performing a patent search focusing on Duchenne muscular 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 9Adapted

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

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

Medicament for treatment of Duchenne muscular dystrophy Inventor(s): Matsuo; Masafumi (3-31, Kitaochiai 5-chome, Suma-ku, Kobe-shi, Hyogo 654-0151, JP), Takeshima; Yasuhiro (Kobe, JP) Assignee(s): Jcr Pharmaceutical Co., Ltd. (hyogo, Jp), Matsuo; Masafumi (hyogo, Jp) Patent Number: 6,653,467 Date filed: September 22, 2000 Abstract: Antisense oligonucleotides comprising a nucleotide sequence complementary to the nucleotide sequence of SEQ ID NO:1 or NO:2 are disclosed. The antisense oligonucleotides are used for treatment of specific types of Duchenne muscular dystrophy which is attributed to a change in number of the nucleotides composing one or more exons adjacent to exon 43 or 53, respectively, in human dystrophin mRNA, wherein the change is due to deletion of one or more nucleotides from the normal nucleotide sequence for the exons, wherein the net of the change in number of the nucleotides is expressed as a reduction of (3.times.N+1) nucleotides, wherein N is zero or a natural number. Excerpt(s): The present invention relates to medicaments for treatment of Duchenne muscular dystrophy, which medicaments are designed to correct an existing shift of the amino acid reading frame in dystrophin pre-mRNA by inducing in a predetermined manner an exon skipping in the pre-mRNA having the reading frame shift resulting from abnormalities in dystrophin gene. More specifically, the present invention relates to splicing enhancer sequences (SES's) in dystrophin gene which can be used for the preparation of medicaments for treatment of certain types of Duchenne muscular dystrophy, as well as to antisense oligonucleotides against the splicing enhancer sequences, and medicaments comprising thereof. Today, it has become possible to diagnose some hereditary diseases caused by abnormal splicing of corresponding premRNA molecules. An intractable disease, muscular dystrophy, has come to draw particular attention. Muscular dystrophy is divided into Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is a hereditary muscular disease of highest incidence, occurring in one in 3,500 live male births. Patients of DMD at first exhibit lowered muscular power in their infancy, suffer from progressive muscular atrophy since then on, and eventually die in their age of around 20. No effective medicament is so far available for DMD, and development of a medicament for it has been longed for by the patients around the world. In 1987, dystrophin gene, which is the causative gene of DMD, was found using retrospective genetics, and BMD also was found to result from abnormality of the same dystrophin gene [Koenig, M. et al., Cell, 50:509-517(1987)]. As for BMD, its onset is relatively late, observed in the adulthood, and nearly normal survival is allowed, although a mild loss of muscular power is observed after the onset of the disease. Dystrophin gene is located in the subregion 21 of the short arm of the X-chromosome. The size of dystrophin gene is 3,0 Mb, the largest known human gene. Despite that large size, it is regions of only 14 kb in total of the dystrophin gene that encodes dystrophin protein, and the encoding regions are divided into no less than 79 exons which are distributed within the gene [Roberts, R G., et al., Genomics, 16:536-538(1993)]. Its pre-mRNA, the transcript of dystrophin gene, undergoes splicing

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into the mature mRNA of 14 kb. The gene includes eight distinct promoter regions, which are also distributed within the gene and responsible for production of respective distinct mRNAs [Nishio, H., et al., J. Clin. Invest., 94:1073-1042(1994), Ann, A H. and Kunkel, L M., Nature Genet., 3:283-291(1993), D'Souza, V N. et al., Hum. Mol. Genet., 4:837-842(1995)]. Thus, dystrophin gene and its transcript are very complex in structure. Web site: http://www.delphion.com/details?pn=US06653467__ •

Method for assaying a human muscular dystrophy protein Inventor(s): Eguchi; Chikahiko (Kawasaki, JP), Ishiguro; Tsuneo (Kawasaki, JP) Assignee(s): Ajinomoto Co., Inc. (tokyo, Jp) Patent Number: 5,340,718 Date filed: January 27, 1993 Abstract: Methods and polypeptides for assaying human proteins associated with Duchenne muscular dystrophy, are disclosed. Excerpt(s): The present invention relates to a method for assaying dystrophin which is a protein defective in a human suffering from Duchenne muscular dystrophy (DMD) which is a hereditary disease. Duchenne muscular dystrophy is a hereditary disease which is developed almost only in males. A gene which is defective peculiarly to this disease is located on the X chromosome and its sequence has been elucidated [M. Konig, E. P. Hoffman, C. J. Bertelson, A. P. Monaco, C. Feenet and L. M. Kunkel: Cell, 50, 509 (1987), E. P. Hoffman, A. P. Monaco, C. C. Feeher and L. M. Kunkel, Science, 238, 347 (1987)]. If any antibody capable of specifically recognizing dystrophin which is a protein encoded by this gene is produced, a deletion or defect of dystrophin specific to this disease could be detected and such would be useful. A related method was tried by Hoffman et al., using the gene from mice suffering from a disease which is the same type as Duchenne muscular dystrophy [E. P. Hoffman, R. H. Brown, Jr. and L. M. Kunkel, Cell, 51, 919 (1987); E. P. Hoffman, C. M. Knudson, K. P. Campbell and L. M. Kunkel, Nature, 330, 754 (1987)]. However, the method of Hoffman et al. uses a gene from mice, the amino acid sequence of which is different by about 10% from that of humans, to produce the antibody so that it is inappropriate to determine dystrophin possessed by humans. Moreover, according to this method, protein having a high molecular weight such as 208 amino acid residues or 410 amino acid residues is used as an antigen and hence, the method has a shortcoming that an antibody capable of reacting not only with dystrophin but also with many other proteins is formed and that the antibody fails to specifically react with dystrophin alone. In order to compensate for the poor specificity of reaction, Hoffman et al. adopted a method using a specimen obtained by previously homogenizing cells to be tested followed by separating protein from the homogenate by electrophoresis, and then performing an antigen-antibody reaction with respect to the specimen. For this reason, the method encounters a drawback that operations are complicated and is thus unsatisfactory. In general, conventional methods for assaying dystrophin have drawbacks in that antibodies capable of specifically reacting only with dystrophin could not be obtained since a gene from a mouse, which is different from that of a human, has been used for preparation of the antibody. Further, operations are complicated since the method comprises using a specimen obtained by previously homogenizing cells to be tested and separating protein from the homogenate by electrophoresis and performing an antigen-antibody reaction with respect to the specimen. Therefore, the present inventors have made extensive investigations to discover a method for assaying the protein in cells in a simple manner,

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by preparing an antiserum capable of specifically reacting only with dystrophin or an antibody fraction separated from the antiserum using a part of dystrophin encoded by human Duchenne muscular dystrophy-associated gene and performing an antigenantibody reaction between a substance to be tested and the antiserum or antibody fraction. Web site: http://www.delphion.com/details?pn=US05340718__

Patent Applications on Duchenne Muscular Dystrophy As of December 2000, U.S. patent applications are open to public viewing.10 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 Duchenne muscular dystrophy: •

DNA sequences encoding dystrophin minigenes and methods of use thereof Inventor(s): Xiao, Xiao; (Wexford, PA) Correspondence: David A. Einhorn, ESQ.; Anderson Kill & Olick, P.C.; 1251 Avenue OF The Americas; New York; NY; 10020; US Patent Application Number: 20030171312 Date filed: April 30, 2001 Abstract: The present invention provides a series of novel dystrophin minigenes that retain the essential biological functions. The expression of the dystrophin minigenes may be controlled by a regulatory element along with a small polyadenylation signal. The entire gene expression cassettes may be readily packaged into a viral vector, preferably an AAV vector. The present invention further defines the minimal functional domains of dystrophin and provides ways to optimize and create new versions of dystrophin minigenes. Finally, the present invention provides a method of treatment for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). Excerpt(s): The present invention relates to novel dystrophin minigenes that retain the essential biological functions of a full length dystrophin gene, and methods of treatment for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in a mammalian subject using the dystrophin minigenes. Duchenne muscular dystrophy (DMD) is an X-linked genetic muscle disease affecting 1 of every 3,500 newborn males (Kunkel et al. Nature (London) 322,73-77 [1986]). The progressive muscle degeneration and weakness usually confine the patients to wheelchairs by their early teens, and lead to death by their early twenties. DMD is caused by recessive mutations in the dystrophin gene, the largest gene known to date, which spans nearly 3 million basepairs on the X-chromosome with 79 exons, a coding sequence of about 11 kb, and a high rate of de novo mutations. (Koenig et al. Cell 50, 509-517 [1987]). Dystrophin is an enormous rod-like protein of 3,685 amino acids (aa) localized beneath the inner surface of muscle cell membrane (Watkins, S. C. et al. Nature 333, 863-866 [1988]). It functions through four major structural domains: a N-terminal domain (1-756 aa), a central rod domain (757-3122 aa), a cysteine rich (CR) domain (3123-3409aa), and a distal C-terminal domain (3410-3685 aa). The N-terminal domain binds to the F-actin of cytoskeletal structures, while the CR domain along with the distal C-terminal domain anchors to the

10

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

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cell membrane via dystrophin-associated protein (DAP) complexes, thus, dystrophin crosslinks and stabilizes the muscle cell membrane and cytoskeleton. The central rod domain contains 24 triple-helix rod repeats (R1-R24) and 4 hinges (H1-H4). Each repeat is approximately 109 aa long. (Koenig et al. J Biol Chem 265, 4560-4566 [1990]). The central rod domain presumably functions as a "shock absorber" during muscle contraction. Dystrophin crosslinks and stabilizes the muscle cell membrane and cytoskeleton. The absence of a functional dystrophin results in the loss of DAP complexes and causes instability of myofiber plasma membrane. These deficiencies in turn lead to chronic muscle damage and degenerative pathology. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of early detection of duchenne muscular dystrophy and other neuromuscular disease Inventor(s): Hampton, Thomas G.; (Framingham, MA) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030003052 Date filed: June 19, 2002 Abstract: The mdx mouse is a model of Duchenne muscular dystrophy. The present invention describes that mdx mice exhibited clinically relevant cardiac phenotypes. A non-invasive method of recording electrocardiograms (ECGs) was used to a study mdx mice (n=15) and control mice (n=15). The mdx mice had significant tachycardia, consistent with observations in patients with muscular dystrophy. Heart-rate was nearly 15% faster in mdx mice than control mice (P<0.01). ECGs revealed significant shortening of the rate-corrected QT interval duration (QTc) in mdx mice compared to control mice (P<0.05). PR interval duration were shorter at baseline in mdx compared to control mice (P<0.05). The muscarinic antagonist atropine significantly increased heart-rate and decreased PR interval duration in C57 mice. Paradoxically, atropine significantly decreased heart-rate and increased PR interval duration in all mdx mice. Pharmacological autonomic blockade and baroreflex sensitivity testing demonstrated an imbalance in autonomic nervous system modulation of heart-rate, with decreased parasympathetic activity and increased sympathetic activity in mdx mice. These electrocardiographic findings in dystrophin-deficient mice provide new bases for diagnosing, understanding, and treating patients with Duchenne muscular dystrophy. Excerpt(s): This application claims priority to U.S. provisional patent application serial No. 60/299,302, filed Jun. 19, 2001, and to U.S. provisional patent application serial No. 60/338,821, filed Nov. 17, 2001. The contents of these provisional patent applications are incorporated herein by reference in their entirety. Dysfunction of the autonomic nervous system is an under-recognized but important aspect of the etiological and clinical manifestation of neuromuscular disorder such as Duchenne muscular dystrophy (DMD). DMD is an X-linked inherited disorder that affects over nearly 30 out of every 100,000 boys born in the United States. The disorder results from a defect in the gene for an enormous protein called dystrophin, which forms part of the scaffold in muscle fibers. Although the disorder is present from the initial stages of fetal development, there is no physical indication at birth that the baby is abnormal. Rarely is there physical diagnosis in the first year of life. Problems are usually not evident until 18 months to 4 years of age. Usually diagnosis is not made until the child is five. Nearly 50% of affected boys do not walk until 18 months of age or later. Duchenne children have difficulty climbing and getting up from the floor. Parents often comment that their child falls

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frequently. By the age 3 to 5 years, generalized muscle weakness becomes more obvious. Parents may be falsely encouraged by a seeming improvement at school age, but this may be due to natural growth and development. Weakness progresses rapidly after age 8 or 9, resulting in the inability to walk or stand unassisted. Leg braces may make walking possible for a year or two, but by early adolescence walking becomes impossible. There are some boys with Duchenne muscular dystrophy who have problems with delay in mental or language development. Eventually all the major muscles are affected. Lung capacity may decrease, resulting in an increased susceptibility to respiratory infections. Cardiac and respiratory failure are common in Duchenne patients. Autonomic nervous system abnormalities have now been frequently reported in patients. The cardiac phenotype includes decreased parasympathetic nervous activity and increased sympathetic nervous activity. Currently there is no reliable mode of prenatal diagnosis or cure. For a series of reasons, diagnosis of Duchenne patients using DNA markers from amniocytes is error ridden and deletion mutants are detectable in only 65% of cases. Therefore, early detection of the disease before locomotor or autonomic disturbances reduce quality of life or irreversibly affect outcome of the disease could significantly improve life-quality prospects and longevity in those afflicted with dystrophin-deficiency related diseases. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Methods for treating muscular dystrophy Inventor(s): Gussoni, Emanuela; (Winchester, MA), Kunkel, Louis M.; (Westwood, MA), Mulligan, Richard C.; (Lincoln, MA), Soneoka, Yuko; (Washington, DC) Correspondence: Hamilton, Brook, Smith & Reynolds, P.C.; 530 Virginia Road; P.O. Box 9133; Concord; MA; 01742-9133; US Patent Application Number: 20020182192 Date filed: March 14, 2002 Abstract: Methods for treating muscle diseases via bone marrow transplantation of either allogeneic cells or autologous cells engineered to express dystrophin or other gene products affected in muscle diseases are disclosed. Bone marrow cells and bone marrow SP cells (a highly purified population of hematopoietic stem cells) can be used in the methods. Muscle diseases include muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy and limb-girdle muscular dystrophies. Excerpt(s): This application is a continuation of International Application No. PCT/US00/25128, filed Sep. 14, 2000, which claims the benefit of U.S. Provisional Application No. 60/153,821, filed Sep. 14, 1999. The teachings of the above applications are incorporated herein by reference in their entirety. There are probably about 3,000 muscle proteins, each encoded by a different gene. Some muscle proteins are part of the structure of muscle fibers, while others influence chemical reactions in the fibers. A defect in a muscle protein gene can lead to a muscle disease. The precise defect in a muscle protein gene can influence the nature and severity of a muscle disease. Muscular dystrophies are caused by defects in muscle protein genes and are typically progressive disorders mainly of striated muscle that lead to breakdown of muscle integrity, often resulting in death. The histologic picture shows variation in fiber size, muscle cell necrosis and regeneration, and often proliferation of connective and adipose tissue. The precise defect in a muscle protein gene determines the nature and severity of a muscular dystrophy. For example, two major types of muscular dystrophy, Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD), are allelic, lethal

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degenerative muscle diseases. DMD results from mutations in the dystrophin gene on the X-chromosome (Hoffinan et al., N. Engl. J. Med., 318:1363-1368 (1988)), which usually result in the absence of dystrophin, a cytoskeletal protein in skeletal and cardiac muscle. BMD is the result of mutations in the same gene (Hoffinan et al., N. Engl. J. Med., 318:1363-1368 (1988)), but dystrophin is usually expressed in muscle but at a reduced level and/or as a shorter, internally deleted form, resulting in a milder phenotype. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical composition for treatment of duchenne muscular dystrophy Inventor(s): Matsuo, Masafumi; (Kobe-shi, JP) Correspondence: Greenblum & Bernstein, P.L.C.; 1941 Roland Clarke Place; Reston; VA; 20191; US Patent Application Number: 20010056077 Date filed: July 31, 2001 Abstract: A therapeutic pharmaceutical composition for patients of Duchenne muscular dystrophy with entire loss of exon 20 in dystrophin mature mRNA is provided. The composition comprise as an active principle an antisense oligonucleotide consisting of a 20 to 50-nucleotide sequence against exon 19 of the dystrophin pre-mRNA. Excerpt(s): This application is a continuation application of U.S. application Ser. No. 09/563,260 filed May 1, 2000, and which claims priority of Japanese Application No. 140930/99, filed May 21, 1999. The entire disclosure of U.S. application Ser. No. 09/563,260 is considered as being part of the disclosure of this application, and the entire disclosure of U.S. application Ser. No. 09/563,260 is expressly incorporated by reference herein in its entirety. The present invention relates to the use of an antisense oligonucleotide for the manufacture of a therapeutic pharmaceutical composition for a certain hereditary disease, and more specifically to a therapeutic pharmaceutical composition for Duchenne muscular dystrophy intended to induce an exon skipping in the pre-mRNA of a certain abnormal dystrophin gene. Antisense oligonucleotide strategy has been widely studied for the purpose of inhibiting expression of oncogenes or viral genes. Antisense oligonucleotides have been known to efficiently inhibit de novo synthesis of their respective targeted proteins. For example, it is known that an antisense oligonucleotide against the mRNA encoding IGF-I (Insulin-like Growth Factor-I) inhibits proliferation of rat glioblastoma cells [Askari, F. K., and McDonnell, W. M., N. Engl. J. Med, 334: 316-318 (1996); Trojan, et al., Science, 259: 94-97 (1993), Trojan, et al., Proc. Natl Acad. Sci. U.S.A., 89: 4874-4878 (1992)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Pharmaceutical composition for treatment of Duchenne muscular dystrophy Inventor(s): Kamei, Shoichiro; (Kobe-shi, JP), Matsuo, Masafumi; (Kobe-shi, JP) Correspondence: Greenblum & Bernstein, P.L.C.; 1941 Roland Clarke Place; Reston; VA; 20191; US Patent Application Number: 20020055481 Date filed: August 16, 2001

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Abstract: The invention provides an isolated and purified DNA set forth as SEQ ID NO:15 in the Sequence Listing and an antisense oligonucleotide complementary to the DNA. The DNA represents the splicing enhancer sequence (SES) in exon 45 of human dystrophin gene, and serves as a template in preparation of the antisense oligonucleotide, which is used to induce exon 45 skipping in certain group of patient with Duchenne muscular dystrophy to restore the reading frame of dystrophin mRNA. Excerpt(s): The present invention relates to pharmaceutical compositions for treatment of Duchenne muscular dystrophy, which pharmaceutical compositions are designed to correct an existing shift of the amino acid reading frame in dystrophin pre-mRNA, by inducing in a predetermined manner an exon skipping in the pre-mRNA having the shifted reading frame as a result of abnormalities in dystrophin gene. More specifically, the present invention relates to a splicing enhancer sequence (SES) in dystrophin gene which can be utilized for the preparation of pharmaceutical compositions for treatment of a specific type of Duchenne muscular dystrophy, as well as to antisense oligonucleotides against the splicing enhancer sequence, and therapeutic pharmaceutical compositions comprising such oligonucleotides. Diagnosis has become available today for hereditary diseases caused by abnormal splicing of pre-mRNA molecules. A so far intractable disease, muscular dystrophy, has thus come to draw particular attention. Muscular dystrophy is divided into two groups: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD is a hereditary muscular disease of the highest incidence, occurring in one in 3,500 live male births. Patients of DMD at first exhibit a lowered muscular power in their infancy, then suffer a constant progression of muscular atrophy thereafter, and eventually die at around the age of 20. It is in contrast to BMD, in which the onset of the disease is relatively late, somewhere in the adulthood, and though a mild loss of muscular power is observed after the onset of the disease, patients can live nearly a normal life. No drug is so far available for effective treatment of DMD, and therefore development of a drug for its treatment has been longed for by the patients across the world. In 1987, dystrophin gene, the causative gene of DMD, was found by means of retrospective genetics, and BMD also was found to result from abnormality in the same dystrophin gene [Koenig, M. et al., Cell, 50:509-517(1987)]. Dystrophin gene is located in the subregion 21 of the short arm of the X-chromosome. The size of the gene is 3.0 Mb, the largest known human gene. Despite that large size, only 14 kb regions in total of the dystrophin gene do encode the whole dystrophin protein, and those encoding regions are divided into no less than 79 exons which are distributed throughout the gene [Roberts, R G., et al., Genomics, 16:536-538(1993)]. The transcript of dystrophin gene, i.e. pre-mRNA, is spliced into the mature 14 kb mRNA. The gene has eight distinct promoter regions also distributed within the gene and they are responsible for production of distinct mRNAs, respectively [Nishio, H., et al., J. Clin. Invest., 94:10731042(1994), Ann, A H. and Kunkel, L M., Nature Genet., 3:283-291(1993), D'Souza, V N. et al., Hum. Mol. Genet., 4:837-842(1995)]. Thus, dystrophin gene and its transcript are structurally very complex. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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TREATMENT OF HEREDITARY DISEASES WITH GENTAMICIN Inventor(s): TREMBLAY, JACQUES P.; (BERNIERES, CA) Correspondence: Denise Huberdeau; Stock Exchange Tower; Suite 3400; 800 Place Victoria P O Box 242; Montreal; H4z1e9; CA Patent Application Number: 20010051607 Date filed: December 22, 1999 Abstract: This invention relates to a method of treating an inherited disease due to a point mutation producing a stop codon by administering an effective dose of an aminoglycoside antibiotic or a derivative thereof. Mdx mouse, which is an animal model for Duchenne muscular dystrophy, has been successfully treated with intramuscularly administered 1 and 5 mg gentamicin, which had for effect to suppress the premature stop mutation by inserting an amino acid at the stop codon. Dystrophin positive muscle fibers not different in number from those of normal mouse were detected at the dose of 5 mg gentamicin. Excerpt(s): Duchenne Muscular Dystrophy (DMD) is due to the mutation of a gene in the X chromosome coding for a protein called dystrophin (Koenig et al. 1987; Hoffman et al. 1987; Bodrug et al. 1987, Arahata et al. 1988; Sugita et al. al 1988). The mutations of the dystrophin vary from one family of patients to another but always lead to the absence of a functional dystrophin protein under the membrane on the muscle fiber (Hoffman et al. 1987; Chelly et al. 1990; Chamberlain et al. 1991; Anderson et al 1992; Kilimann et al. 1992; Roberts et al 1992). The absence of dystrophin leads to an increase vulnerability of the muscle fibers during contraction (Menke 1995). Repeated cycles of damages and repairs produce a progressive reduction of the number of muscle fibers and to loss of strength which confine the patients to a wheel chair by the age of ten and to premature death in their early twenties. Roughly 70% of the mutations of the dystrophin gene are large deletion of one of several exons (Anderson et al 1992; Kilimann et al. 1992). The other mutations are small point mutations due either to a small deletion of a few base pairs leading to a shift of the reading frame or changes of only one base pair producing a missense or a stop codon (Bullman et al 1991: Chamberlain et al. 1994; Roberts et al. 1992; Clemens et al 1992; Nicholson et al. 1993). Around 5% of all DMD mutations may be due to stop codons. Cystic fibrosis (CF) is due to a mutation of a gene coding for the CF transmembrane conductance regulator (CFTR) protein. Howard et al. (1996) made experiments with a bronchial epithelial cell line obtained from a CF patient having a premature stop mutation in the CFTR gene. This mutation resulted in a premature end of the synthesis of the CFTR protein and thus in a non-functional protein. They incubated this cell line with aminoglycoside antibiotics G418 (100 mg/mL) or with gentamicin (200 mg/mL) during 18 to 24 hours. This incubation with gentamicin permitted to suppress the premature stop mutation by inserting an amino acid at the stop codon. A full-length CFTR protein was thus obtained. The suppression of the premature stop codon by gentamicin is mediated by mis-pairing between the stop codon and a near-cognate aminoacyl tRNA. Bedwell et al. (1997) recently demonstrated that this full length CFTR protein resulting from the incubation with the aminoglycoside antibiotics was present in the cell membrane and functional. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of chimeric mutational vectors to change endogenous nucleotide sequences in solid tissues Inventor(s): Bartlett, Richard J.; (Weston, FL), Rando, Thomas A.; (Stanford, CA) Correspondence: Pillsbury Winthrop, Llp; P.O. Box 10500; Mclean; VA; 22102; US Patent Application Number: 20020137717 Date filed: February 20, 2002 Abstract: This invention relates to the field of muscular dystrophy and methods for its treatment in humans. This invention also concerns art-recognized animal models of Duchenne muscular dystrophy in dogs (GRMD) and mice (mdx). Another aspect concerns chimeric mutational vectors capable of inducing reversion of genetic mutations (i.e., gene repair) causing genetic disease by direct injection into affected tissue. Thus, more generally, the invention envisions direct injection of chimeric mutational vectors into affected tissues to effect gene repair therein. Excerpt(s): This is a continuation application which claims priority benefit to U.S. patent application Ser. No. 09/576,081, filed May 20, 2000, which claims priority benefit to provisional U.S. Appln. No. 60/135,139, filed May 21, 1999, and provisional U.S. Appln. No. 60/174,388, filed Jan. 5, 2000, all of which are incorporated by reference herein. The invention concerns methods of treating genetic diseases or other pathologic conditions by making one or more specific changes in endogenous nucleotide sequences of solid tissues. These specific changes are mediated by oligonucleobases called chimeric mutational vectors (CMV). The CMV can be administered directly to the subject in vivo; in particular, the CMV can be injected into a solid tissue in which expression of the mutated gene occurs. Such gene repair can reverse the disease or other pathologic condition caused by the mutation or, alternatively, can introduce a second change that compensates for the disease or condition causing mutation. The inclusion of a reference in this section is not to be understood as an admission that its teachings were publicly available prior to our invention of the subject matter disclosed herein or that they resulted from someone other than the inventors. 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 Duchenne muscular 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 “Duchenne muscular 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 Duchenne muscular dystrophy. You can also use this procedure to view pending patent applications concerning Duchenne muscular 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 7. DYSTROPHY

BOOKS

ON

DUCHENNE

MUSCULAR

Overview This chapter provides bibliographic book references relating to Duchenne muscular dystrophy. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Duchenne muscular 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.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “Duchenne muscular dystrophy” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on Duchenne muscular dystrophy: •

A-Z Reference Book of Syndromes and Inherited Disorders Source: London, England: Chapman and Hall. 1996. 394 p. Contact: Available from Singular Publishing Group, Inc. 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545 or (619) 238-6777. Fax (800) 774-8398 or (619) 238-6789. E-mail: [email protected]. Website: www.singpub.com. PRICE: $42.95 plus shipping and handling. ISBN: 0412641208. Summary: This book provides a practical reference for both caregivers and those with a syndrome or inherited disorder. The author describes the disorders and problems of both children and adults, and considers the day-to-day management of conditions. The book is written in nontechnical language while still providing enough detail for medical, nursing, and midwifery professionals. The syndromes and disorders are listed

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alphabetically by name. Those specifically related to deafness, communication, and speech and language include achondroplasia, Alport's syndrome, Apert's syndrome, Asperger's syndrome, Batten's disease, Beckwith-Wiedeman syndrome, CHARGE syndrome, Cockayne syndrome, Cornelia de Lange syndrome, Crouzon's syndrome, Down's syndrome, Duchenne muscular dystrophy, Edward's syndrome, Ehlers-Danlos syndrome, Fabry disease, fetal alcohol syndrome, Fragile X syndrome, Gilles de la Tourette syndrome, Goldenhar syndrome, Hunter's syndrome, Hurler's syndrome, Klinefelter's syndrome, LEOPARD syndrome, Moebius syndrome, Morquio's syndrome, neurofibromatosis, Niemann-Pick disease, Noonan's syndrome, osteogenesis imperfecta, Pierre-Robin syndrome, Prader-Willi syndrome, Rett's syndrome, Reye's syndrome, San Filippo syndrome, Smith-Magenis syndrome, Stickler syndrome, Tay-Sachs disease, Treacher Collins syndrome, Turner's syndrome, Usher's syndrome, Waardenburg's syndrome, and William's syndrome. For each syndrome, the author lists alternative names, incidence, causation (etiology), characteristics or symptoms, management implications (treatment options), prognosis, and self-help groups to contact. Most groups listed are in England. The book concludes with three appendices that provide a discussion of genetics, a listing of regional genetics centers (in England), and a glossary of terms. A subject index is also included. (AA-M).

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “Duchenne muscular dystrophy” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Duchenne muscular dystrophy” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Duchenne muscular dystrophy” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Duchenne Muscular Dystrophy by Alan E. H. Emery, Francesco Muntoni; ISBN: 0198515316; http://www.amazon.com/exec/obidos/ASIN/0198515316/icongroupinterna

•

Duchenne Muscular Dystrophy (Oxford Medical Publicati Ons) by Alan E. H. Emery; ISBN: 0192623702; http://www.amazon.com/exec/obidos/ASIN/0192623702/icongroupinterna

•

Duchenne Muscular Dystrophy: Animal Models and Genetic Manipulation by Byron A. Kakulas (Editor), et al; ISBN: 0881679380; http://www.amazon.com/exec/obidos/ASIN/0881679380/icongroupinterna

•

The History of a Genetic Disease: Duchenne Muscular Dystrophy or Meryon's Disease by Alan E.H. Emery, Marcia L.H. Emery; ISBN: 1853152498; http://www.amazon.com/exec/obidos/ASIN/1853152498/icongroupinterna

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Chapters on Duchenne Muscular Dystrophy In order to find chapters that specifically relate to Duchenne muscular dystrophy, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Duchenne muscular 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 “Duchenne muscular dystrophy” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Duchenne muscular dystrophy: •

Muscular Dystrophy: Duchenne Muscular Dystrophy, Becker Muscular Dystrophy 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. 180-185. Contact: Available from Charles C Thomas Publisher. 2600 South First Street, Springfield, IL 62794-9265. (212) 789-8980. Fax (217) 789-9130. PRICE: $75.95 plus shipping and handling (cloth); $39.95 plus shipping and handling (paper). ISBN: 0398058393. Summary: Both Duchenne and Becker muscular dystrophy are progressive muscle wasting conditions that primarily affect boys. This chapter on muscular 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 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. 5 references.

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CHAPTER 8. PERIODICALS AND NEWS ON DUCHENNE MUSCULAR DYSTROPHY Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Duchenne muscular dystrophy.

News Services and Press Releases One of the simplest ways of tracking press releases on Duchenne muscular 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 “Duchenne muscular 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 Duchenne muscular 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 “Duchenne muscular dystrophy” (or synonyms). The following was recently listed in this archive for Duchenne muscular dystrophy: •

New approach repairs genetic defect in Duchenne muscular dystrophy mouse model Source: Reuters Medical News Date: July 07, 2003

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"Valley sign" a new diagnostic tool for Duchenne muscular dystrophy Source: Reuters Medical News Date: July 29, 2002

•

Benefit seen with long-term deflazacort for Duchenne muscular dystrophy Source: Reuters Industry Breifing Date: February 27, 2001

•

Duchenne Muscular Dystrophy: Noninvasive Respiratory Protocol Effective Source: Reuters Medical News Date: October 31, 1997

•

Duchenne Muscular Dystrophy: A Better Mouse Model Built Source: Reuters Medical News Date: August 25, 1997

•

TGF-Beta-1 Expression Initiates Fibrosis In Duchenne Muscular Dystrophy Source: Reuters Medical News Date: August 22, 1995 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 “Duchenne muscular 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

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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Duchenne muscular dystrophy” (or synonyms). If you know the name of a company that is relevant to Duchenne muscular 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 “Duchenne muscular dystrophy” (or synonyms).

Academic Periodicals covering Duchenne Muscular Dystrophy Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Duchenne muscular dystrophy. In addition to these sources, you can search for articles covering Duchenne muscular 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

119

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 Institute11: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

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/

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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.12 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:13 •

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

•

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

•

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

•

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/

•

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

•

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

•

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/

•

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

12

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). 13 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 Gateway14 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.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Duchenne muscular 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 3862 32 234 1 80 4209

HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 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.18 Simply search by “Duchenne muscular dystrophy” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

14

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

15

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). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18

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 Biologists19 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.20 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.21 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/.

19 Adapted 20

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. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Duchenne muscular 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 Duchenne muscular 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 Duchenne muscular 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 “Duchenne muscular dystrophy”:

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Other guides Amyotrophic Lateral Sclerosis http://www.nlm.nih.gov/medlineplus/amyotrophiclateralsclerosis.html Charcot-Marie-Tooth Disease http://www.nlm.nih.gov/medlineplus/charcotmarietoothdisease.html Metabolic Disorders http://www.nlm.nih.gov/medlineplus/metabolicdisorders.html Muscular Dystrophy http://www.nlm.nih.gov/medlineplus/musculardystrophy.html Muscle Disorders http://www.nlm.nih.gov/medlineplus/muscledisorders.html Neuromuscular Disorders http://www.nlm.nih.gov/medlineplus/neuromusculardisorders.html Spinal Muscular Atrophy http://www.nlm.nih.gov/medlineplus/spinalmuscularatrophy.html

Within the health topic page dedicated to Duchenne muscular dystrophy, the following was listed: •

Diagnosis/Symptoms Accurate and Affordable Diagnosis of Duchenne Muscular Dystrophy Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_dmd_test.htm Creatine Kinase Test Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q71ss-cktest.html Electromyography and Nerve Conduction Velocities Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q75ss.html Muscle Biopsies Source: Muscular Dystrophy Association http://www.mdausa.org/publications/Quest/q74ss.html

•

Treatment Treatment for Duchenne MD: Braces and Wheelchairs Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/treatment/braces.html Treatment for Duchenne MD: Physical Therapy Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/treatment/physical.html Treatment for Duchenne MD: Seating Requirements for Boys with MD Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/treatment/seating_req.html

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Treatment for Duchenne MD: Steroids / Nutritional Supplements / Antibiotics Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/treatment/supplements.html Treatment for Duchenne MD: Surgery for Scoliosis Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/treatment/surgery.html •

Coping 101 Hints to “Help-with-Ease” for Patients with Neuromuscular Disease Source: Muscular Dystrophy Association http://www.mdausa.org/publications/101hints/ Learning to Live with Neuromuscular Disease: A Message for Parents Source: Muscular Dystrophy Association http://www.mdausa.org/publications/learning/index.html Parents & Family: Connecting with Your Son Who Has Duchenne MD Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/emotional/connecting.html Parents & Family: Daily Life with Duchenne MD Source: Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/emotional/life.html

•

Specific Conditions/Aspects Facts about Duchenne and Becker Muscular Dystrophies (DMD and BMD) Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-dmdbmd-what.html Facts about Facioscapulohumeral Muscular Dystrophy Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-fshd.html Facts about Limb-Girdle Muscular Dystrophy (LGMD) Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-lgmd-qa.html Facts about Myotonic Muscular Dystrophy Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-mmd-qa.html Facts about Rare Muscular Dystrophies: Congenital, Distal, Emery-Dreifuss and Oculopharyngeal Muscular Dystrophies Source: Muscular Dystrophy Association http://www.mdausa.org/publications/fa-rareMD.html Lambert-Eaton Myasthenic Syndrome Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/lambert-eaton.htm

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Children Everybody's Different Nobody's Perfect Source: Muscular Dystrophy Association http://www.mdausa.org/publications/nobody/index.html Meaning of Muscular Dystrophy Source: Nemours Foundation http://kidshealth.org/kid/health_problems/bone/muscular_dystrophy.html

•

From the National Institutes of Health Muscular Dystrophy (MD) Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/health_and_medical/disorders/md.htm

•

Latest News Quebec Researchers Report Promising Lead for Fatal Hereditary Disease Source: 02/18/2004, Canadian Press http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_16145 .html

•

Organizations Muscular Dystrophy Association http://www.mdausa.org/ National Institute of Arthritis and Musculoskeletal and Skin Diseases http://www.niams.nih.gov/ National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/ Parent Project for Muscular Dystrophy Research http://www.parentprojectmd.org/

•

Research Faulty Muscle Repair Implicated in Muscular Dystrophies Source: National Institute of Neurological Disorders and Stroke http://www.ninds.nih.gov/news_and_events/news_article_md_repair.htm MDA Research Advances Rapidly Source: Muscular Dystrophy Association http://www.mdausa.org/publications/resdev.html

•

Teenagers Making Sense of Muscular Dystrophy Source: Nemours Foundation http://kidshealth.org/teen/diseases_conditions/bones/muscular_dystrophy.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

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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. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Understanding Duchenne Muscular Dystrophy Summary: This document provides information on the causes, symptoms, and diagnosis of muscular dystrophy. Source: Parent Project for Muscular Dystrophy Research, Inc. http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=7772 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 Duchenne muscular 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. 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

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Duchenne muscular dystrophy. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Duchenne muscular 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 Duchenne muscular 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 “Duchenne muscular 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 your search to “Organizations” and “Duchenne muscular 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 “Duchenne muscular dystrophy” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Duchenne muscular 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.22

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

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

22

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

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •

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

•

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

•

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

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

•

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

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

•

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/

23

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

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•

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

•

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

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

•

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/

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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

•

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

•

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

•

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

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

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

•

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

•

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

•

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

•

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

•

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

•

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

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

Basic Guidelines for Duchenne Muscular Dystrophy Duchenne muscular dystrophy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm

•

Signs & Symptoms for Duchenne Muscular Dystrophy Breathing difficulties Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003075.htm Contractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003185.htm Cough Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003072.htm Difficulty walking Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003199.htm

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Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Fever Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003090.htm Lack of coordination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003198.htm Muscle Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle contractures Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Muscle wasting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003188.htm Muscle weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Wasting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003188.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm •

Diagnostics and Tests for Duchenne Muscular Dystrophy BAL Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003858.htm Biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003416.htm CPK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm Electromyography Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm EMG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003929.htm Muscle biopsy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003924.htm Serum CPK Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003503.htm

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Nutrition for Duchenne Muscular Dystrophy Protein Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002467.htm

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Background Topics for Duchenne Muscular Dystrophy Aspiration Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002216.htm Muscular dystrophy - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002154.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm

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

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

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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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DUCHENNE MUSCULAR DYSTROPHY DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acetylcholinesterase: An enzyme that catalyzes the hydrolysis of acetylcholine to choline and acetate. In the CNS, this enzyme plays a role in the function of peripheral neuromuscular junctions. EC 3.1.1.7. [NIH] Actin: Essential component of the cell skeleton. [NIH] Actinin: A protein factor that regulates the length of R-actin. It is chemically similar, but immunochemically distinguishable from actin. [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 Deaminase: An enzyme that catalyzes the hydrolysis of adenosine to inosine with the elimination of ammonia. Since there are wide tissue and species variations in the enzyme, it has been used as a tool in the study of human and animal genetics and in medical diagnosis. EC 3.5.4.4. [NIH] Adenovirus: A group of viruses that cause respiratory tract and eye infections. Adenoviruses used in gene therapy are altered to carry a specific tumor-fighting gene. [NIH] Adipose Tissue: Connective tissue composed of fat cells lodged in the meshes of areolar tissue. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH]

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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] 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] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Aged, 80 and Over: A person 80 years of age and older. [NIH] Agrin: A protein component of the synaptic basal lamina. It has been shown to induce clustering of acetylcholine receptors on the surface of muscle fibers and other synaptic molecules in both synapse regeneration and development. [NIH] Air Embolism: Occurs when the lungs over expand to the point that air bubbles are forced through the air sacs of the lungs into the circulatory system. [NIH] Air Sacs: Thin-walled sacs or spaces which function as a part of the respiratory system in birds, fishes, insects, and mammals. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allogeneic: Taken from different individuals of the same species. [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

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different. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnion: The extraembryonic membrane which contains the embryo and amniotic fluid. [NIH]

Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] 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

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of surgery or other painful procedures. [NIH] Angiogenesis: Blood vessel formation. Tumor angiogenesis is the growth of blood vessels from surrounding tissue to a solid tumor. This is caused by the release of chemicals by the tumor. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antiserum: The blood serum obtained from an animal after it has been immunized with a particular antigen. It will contain antibodies which are specific for that antigen as well as antibodies specific for any other antigen with which the animal has previously been immunized. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the

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physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [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] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autologous: Taken from an individual's own tissues, cells, or DNA. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress.

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Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]

Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Base Sequence: The sequence of purines and pyrimidines in nucleic acids and polynucleotides. It is also called nucleotide or nucleoside sequence. [NIH] Basement Membrane: Ubiquitous supportive tissue adjacent to epithelium and around smooth and striated muscle cells. This tissue contains intrinsic macromolecular components such as collagen, laminin, and sulfated proteoglycans. As seen by light microscopy one of its subdivisions is the basal (basement) lamina. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioengineering: The application of engineering principles to the solution of biological problems, for example, remote-handling devices, life-support systems, controls, and displays. [NIH] Biogenesis: The origin of life. It includes studies of the potential basis for life in organic compounds but excludes studies of the development of altered forms of life through mutation and natural selection, which is evolution. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain

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mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] 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 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] Body Composition: The relative amounts of various components in the body, such as percent body fat. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [NIH]

Calcium: A basic element found in nearly all organized tissues. It is a member of the

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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] Calpain: Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including neuropeptides, cytoskeletal proteins, proteins from smooth muscle, cardiac muscle, liver, platelets and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. [NIH] Capping: A 7-methyl guanosine cap attached to the 5'-end of eucaryotic mRNAs by a phosphodiester linkage. The cap is believed to increase the stability of the message, since most nucleases require a 5'-3'or 3'-5'bond in order to cleave the RNA. [NIH] Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid. [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] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiomyoplasty: A surgical procedure that involves detaching one end of a back muscle and attaching it to the heart. An electric stimulator causes the muscle to contract to pump blood from the heart. [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] 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] Catabolism: Any destructive metabolic process by which organisms convert substances into excreted compounds. [EU] Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from

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tyrosine. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caveolae: Endocytic/exocytic cell membrane structures rich in glycosphingolipids, cholesterol, and lipid-anchored membrane proteins that function in endocytosis (potocytosis), transcytosis, and signal transduction. Caveolae assume various shapes from open pits to closed vesicles. Caveolar coats are composed of caveolins. [NIH] Caveolins: The main structural proteins of caveolae. Several distinct genes for caveolins have been identified. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Adhesion: Adherence of cells to surfaces or to other cells. [NIH] Cell Adhesion Molecules: Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis. [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 Lineage: The developmental history of cells as traced from the first division of the original cell or cells in the embryo. [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 Membrane Structures: Structures which are part of the cell membrane or have cell membrane as a major part of their structure. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. [NIH] Cell Transplantation: Transference of cells within an individual, between individuals of the same species, or between individuals of different species. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and

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learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [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] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemokines: Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C (chemokines, C), CC (chemokines, CC), and CXC (chemokines, CXC), according to variations in a shared cysteine motif. [NIH] Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chimeric Proteins: Proteins in individuals that are derived from genetically different zygotes. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chondrocytes: Polymorphic cells that form cartilage. [NIH] Chondroitin sulfate: The major glycosaminoglycan (a type of sugar molecule) in cartilage. [NIH]

Chorioretinitis: Inflammation of the choroid in which the sensory retina becomes edematous and opaque. The inflammatory cells and exudate may burst through the sensory retina to cloud the vitreous body. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU]

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Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Circulatory system: The system that contains the heart and the blood vessels and moves blood throughout the body. This system helps tissues get enough oxygen and nutrients, and it helps them get rid of waste products. The lymph system, which connects with the blood system, is often considered part of the circulatory system. [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] Clear cell carcinoma: A rare type of tumor of the female genital tract in which the inside of the cells looks clear when viewed under a microscope. [NIH] Cleave: A double-stranded cut in DNA with a restriction endonuclease. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2.

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Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementation: The production of a wild-type phenotype when two different mutations are combined in a diploid or a heterokaryon and tested in trans-configuration. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Concentric: Having a common center of curvature or symmetry. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Conduction: The transfer of sound waves, heat, nervous impulses, or electricity. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH]

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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known conserved sequence set is represented by a consensus sequence. Commonly observed supersecondary protein structures (amino acid motifs) are often formed by conserved sequences. [NIH] Conserved Sequence: A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a consensus sequence. Amino acid motifs are often composed of conserved sequences. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [NIH] Contamination: The soiling or pollution by inferior material, as by the introduction of organisms into a wound, or sewage into a stream. [EU] Continuum: An area over which the vegetation or animal population is of constantly changing composition so that homogeneous, separate communities cannot be distinguished. [NIH]

Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contracture: A condition of fixed high resistance to passive stretch of a muscle, resulting from fibrosis of the tissues supporting the muscles or the joints, or from disorders of the muscle fibres. [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] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Corpuscle: A small mass or body; a sensory nerve end bulb; a cell, especially that of the blood or the lymph. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance;

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and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Creatine: An amino acid that occurs in vertebrate tissues and in urine. In muscle tissue, creatine generally occurs as phosphocreatine. Creatine is excreted as creatinine in the urine. [NIH]

Creatine Kinase: A transferase that catalyzes formation of phosphocreatine from ATP + creatine. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic isoenzymes have been identified in human tissues: MM from skeletal muscle, MB from myocardial tissue, and BB from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins. EC 2.7.3.2. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] 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] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] Cytotoxic: Cell-killing. [NIH] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH]

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De novo: In cancer, the first occurrence of cancer in the body. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] 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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] DES: Diethylstilbestrol. A synthetic hormone that was prescribed from the early 1940s until 1971 to help women with complications of pregnancy. DES has been linked to an increased risk of clear cell carcinoma of the vagina in daughters of women who used DES. DES may also increase the risk of breast cancer in women who used DES. [NIH] Desmin: An intermediate filament protein found predominantly in smooth, skeletal, and cardiac muscle cells. Localized at the Z line. MW 50,000 to 55,000 is species dependent. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. [NIH] Dislocation: The displacement of any part, more especially of a bone. Called also luxation. [EU]

Dissection: Cutting up of an organism for study. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is

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roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] 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] Dystrophic: Pertaining to toxic habitats low in nutrients. [NIH] Dystrophin: A muscle protein localized in surface membranes which is the product of the Duchenne/Becker muscular dystrophy gene. Individuals with Duchenne muscular dystrophy usually lack dystrophin completely while those with Becker muscular dystrophy have dystrophin of an altered size. It shares features with other cytoskeletal proteins such as spectrin and alpha-actinin but the precise function of dystrophin is not clear. One possible role might be to preserve the integrity and alignment of the plasma membrane to the myofibrils during muscle contraction and relaxation. MW 400 kDa. [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] Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] 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.,

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radiation. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [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] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Energy Intake: Total number of calories taken in daily whether ingested or by parenteral routes. [NIH] Enhancer: Transcriptional element in the virus genome. [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] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiological: Relating to, or involving epidemiology. [EU] 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]

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Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Erythrocyte Membrane: The semipermeable outer portion of the red corpuscle. It is known as a 'ghost' after hemolysis. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Escalation: Progressive use of more harmful drugs. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor, cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [EU] Eye Infections: Infection, moderate to severe, caused by bacteria, fungi, or viruses, which occurs either on the external surface of the eye or intraocularly with probable inflammation, visual impairment, or blindness. [NIH] Facial: Of or pertaining to the face. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fasciculation: A small local contraction of muscles, visible through the skin, representing a spontaneous discharge of a number of fibres innervated by a single motor nerve filament. [EU]

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.

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[NIH]

Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetal Alcohol Syndrome: A disorder occurring in children born to alcoholic women who continue to drink heavily during pregnancy. Common abnormalities are growth deficiency (prenatal and postnatal), altered morphogenesis, mental deficiency, and characteristic facies - small eyes and flattened nasal bridge. Fine motor dysfunction and tremulousness are observed in the newborn. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibroblast Growth Factor: Peptide isolated from the pituitary gland and from the brain. It is a potent mitogen which stimulates growth of a variety of mesodermal cells including chondrocytes, granulosa, and endothelial cells. The peptide may be active in wound healing and animal limb regeneration. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fine-needle aspiration: The removal of tissue or fluid with a needle for examination under a microscope. Also called needle biopsy. [NIH] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flexion: In gynaecology, a displacement of the uterus in which the organ is bent so far forward or backward that an acute angle forms between the fundus and the cervix. [EU] 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] Fovea: The central part of the macula that provides the sharpest vision. [NIH] Frameshift: A type of mutation which causes out-of-phase transcription of the base sequence; such mutations arise from the addition or delection of nucleotide(s) in numbers

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other than 3 or multiples of 3. [NIH] Frameshift Mutation: A type of mutation in which a number of nucleotides not divisible by three is deleted from or inserted into a coding sequence, thereby causing an alteration in the reading frame of the entire sequence downstream of the mutation. These mutations may be induced by certain types of mutagens or may occur spontaneously. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fundus: The larger part of a hollow organ that is farthest away from the organ's opening. The bladder, gallbladder, stomach, uterus, eye, and cavity of the middle ear all have a fundus. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gait: Manner or style of walking. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Juices: Liquids produced in the stomach to help break down food and kill bacteria. [NIH]

Gastric Mucosa: Surface epithelium in the stomach that invaginates into the lamina propria, forming gastric pits. Tubular glands, characteristic of each region of the stomach (cardiac, gastric, and pyloric), empty into the gastric pits. The gastric mucosa is made up of several different kinds of cells. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Gene 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

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diseases, hemoglobinopathies, and leukemias and may also prove useful in restoring drug sensitivity, particularly for leukemia. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genomics: The systematic study of the complete DNA sequences (genome) of organisms. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glioblastoma: A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [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] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutamine: A non-essential amino acid present abundantly throught the body and is involved in many metabolic processes. It is synthesized from glutamic acid and ammonia. It is the principal carrier of nitrogen in the body and is an important energy source for many cells. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]

Glycerol Kinase: An enzyme that catalyzes the formation of glycerol 3-phosphate from ATP and glycerol. Dihydroxyacetone and L-glyceraldehyde can also act as acceptors; UTP and, in the case of the yeast enzyme, ITP and GTP can act as donors. It provides a way for glycerol derived from fats or glycerides to enter the glycolytic pathway. EC 2.7.1.30. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH]

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Glycosaminoglycan: A type of long, unbranched polysaccharide molecule. Glycosaminoglycans are major structural components of cartilage and are also found in the cornea of the eye. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Survival: The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Growth factors: Substances made by the body that function to regulate cell division and cell survival. Some growth factors are also produced in the laboratory and used in biological therapy. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematopoietic Stem Cells: Progenitor cells from which all blood cells derive. [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] Hemolysis: The destruction of erythrocytes by many different causal agents such as antibodies, bacteria, chemicals, temperature, and changes in tonicity. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heparan Sulfate Proteoglycan: A substance released by astrocytes, which is critical in stopping nervous fibers in their tracks. [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.

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2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homogenate: A suspension of animal tissue that is ground in the all-glass "homogenizer" described by Potter and Elvehjem in 1936. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [EU] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hybridization: The genetic process of crossbreeding to produce a hybrid. Hybrid nucleic acids can be formed by nucleic acid hybridization of DNA and RNA molecules. Protein hybridization allows for hybrid proteins to be formed from polypeptide chains. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] 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] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] 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] Ichthyosis: Any of several generalized skin disorders characterized by dryness, roughness, and scaliness, due to hypertrophy of the stratum corneum epidermis. Most are genetic, but some are acquired, developing in association with other systemic disease or genetic syndrome. [NIH]

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Ichthyosis Vulgaris: Most common form of ichthyosis characterized by prominent scaling especially on the exterior surfaces of the extremities. It is inherited as an autosomal dominant trait. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

Immunoglobulin: A protein that acts as an antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In 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] Incubated: Grown in the laboratory under controlled conditions. (For instance, white blood cells can be grown in special conditions so that they attack specific cancer cells when returned to the body.) [NIH] Incubation: The development of an infectious disease from the entrance of the pathogen to the appearance of clinical symptoms. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] Infant, Newborn: An infant during the first month after birth. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local

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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] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] 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] Insufflation: The act of blowing a powder, vapor, or gas into any body cavity for experimental, diagnostic, or therapeutic purposes. [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] Intermediate Filament Proteins: Filaments 7-11 nm in diameter found in the cytoplasm of all cells. Many specific proteins belong to this group, e.g., desmin, vimentin, prekeratin, decamin, skeletin, neurofilin, neurofilament protein, and glial fibrillary acid protein. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intraperitoneal: IP. Within the peritoneal cavity (the area that contains the abdominal organs). [NIH] Intravascular: Within a vessel or vessels. [EU] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Introns: Non-coding, intervening sequences of DNA that are transcribed, but are removed from within the primary gene transcript and rapidly degraded during maturation of messenger RNA. Most genes in the nuclei of eukaryotes contain introns, as do mitochondrial and chloroplast genes. [NIH] 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]

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Invertebrates: Animals that have no spinal column. [NIH] Involuntary: Reaction occurring without intention or volition. [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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isoenzyme: Different forms of an enzyme, usually occurring in different tissues. The isoenzymes of a particular enzyme catalyze the same reaction but they differ in some of their properties. [NIH] Isolated limb perfusion: A technique that may be used to deliver anticancer drugs directly to an arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lacrimal: Pertaining to the tears. [EU] Laminin: Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. [NIH] Language Development: The gradual expansion in complexity and meaning of symbols and sounds as perceived and interpreted by the individual through a maturational and learning process. Stages in development include babbling, cooing, word imitation with cognition, and use of short sentences. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Lethal: Deadly, fatal. [EU] Leukemia: Cancer of blood-forming tissue. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limb perfusion: A technique that may be used to deliver anticancer drugs directly to an

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arm or leg. The flow of blood to and from the limb is temporarily stopped with a tourniquet, and anticancer drugs are put directly into the blood of the limb. This allows the person to receive a high dose of drugs in the area where the cancer occurred. [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipodystrophy: A collection of rare conditions resulting from defective fat metabolism and characterized by atrophy of the subcutaneous fat. They include total, congenital or acquired, partial, abdominal infantile, and localized lipodystrophy. [NIH] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol, and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] 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] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] 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] Lucida: An instrument, invented by Wollaton, consisting essentially of a prism or a mirror through which an object can be viewed so as to appear on a plane surface seen in direct view and on which the outline of the object may be traced. [NIH] Luciferase: Any one of several enzymes that catalyze the bioluminescent reaction in certain marine crustaceans, fish, bacteria, and insects. The enzyme is a flavoprotein; it oxidizes luciferins to an electronically excited compound that emits energy in the form of light. The color of light emitted varies with the organism. The firefly enzyme is a valuable reagent for measurement of ATP concentration. (Dorland, 27th ed) EC 1.13.12.-. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Luminescence: The property of giving off light without emitting a corresponding degree of heat. It includes the luminescence of inorganic matter or the bioluminescence of human

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matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [NIH] Luxation: The displacement of the particular surface of a bone from its normal joint, without fracture. [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] 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] 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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant tumor: A tumor capable of metastasizing. [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] Mazindol: Tricyclic anorexigenic agent unrelated to and less toxic than amphetamine, but with some similar side effects. It inhibits uptake of catecholamines and blocks the binding of cocaine to the dopamine uptake transporter. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] 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

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with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [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] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental deficiency: A condition of arrested or incomplete development of mind from inherent causes or induced by disease or injury. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] 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] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH] Midwifery: The practice of assisting women in childbirth. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mitochondria: Parts of a cell where aerobic production (also known as cell respiration) takes place. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei

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normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]

Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] 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] Morphogenesis: The development of the form of an organ, part of the body, or organism. [NIH]

Morphological: Relating to the configuration or the structure of live organs. [NIH] Morphology: The science of the form and structure of organisms (plants, animals, and other forms of life). [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Motor Neurons: Neurons which activate muscle cells. [NIH] Motor Skills: Performance of complex motor acts. [NIH] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Muscle Fibers: Large single cells, either cylindrical or prismatic in shape, that form the basic unit of muscle tissue. They consist of a soft contractile substance enclosed in a tubular sheath. [NIH] Muscle Hypertonia: Abnormal increase in skeletal or smooth muscle tone. Skeletal muscle

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hypertonicity may be associated with pyramidal tract lesions or basal ganglia diseases. [NIH] Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSIN. More than a dozen accessary proteins exist including troponin, tropomyosin, and dystrophin. [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] Mutagens: Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myeloid Cells: Cells which include the monocytes and the granulocytes. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myofibrils: Highly organized bundles of actin, myosin, and other proteins in the cytoplasm of skeletal and cardiac muscle cells that contract by a sliding filament mechanism. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Natural selection: A part of the evolutionary process resulting in the survival and reproduction of the best adapted individuals. [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] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Needle biopsy: The removal of tissue or fluid with a needle for examination under a microscope. Also called fine-needle aspiration. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [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

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ganglia. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Diseases: A general term encompassing lower motor neuron disease; peripheral nervous system diseases; and certain muscular diseases. Manifestations include muscle weakness; fasciculation; muscle atrophy; spasm; myokymia; muscle hypertonia, myalgias, and musclehypotonia. [NIH] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropeptides: Peptides released by neurons as intercellular messengers. Many neuropeptides are also hormones released by non-neuronal cells. [NIH] Neuroretinitis: Inflammation of the optic nerve head and adjacent retina. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Night Blindness: Anomaly of vision in which there is a pronounced inadequacy or complete absence of dark-adaptation. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Envelope: The membrane system of the cell nucleus that surrounds the nucleoplasm. It consists of two concentric membranes separated by the perinuclear space. The structures of the envelope where it opens to the cytoplasm are called the nuclear pores (nuclear pore). [NIH] Nuclear Pore: An opening through the nuclear envelope formed by the nuclear pore complex which transports nuclear proteins or RNA into or out of the cell nucleus and which, under some conditions, acts as an ion channel. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH]

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Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleic Acid Hybridization: The process whereby two single-stranded polynucleotides form a double-stranded molecule, with hydrogen bonding between the complementary bases in the two strains. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] 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]

Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Oncogenes: Genes which can potentially induce neoplastic transformation. They include genes for growth factors, growth factor receptors, protein kinases, signal transducers, nuclear phosphoproteins, and transcription factors. When these genes are constitutively expressed after structural and/or regulatory changes, uncontrolled cell proliferation may result. Viral oncogenes have prefix "v-" before the gene symbol; cellular oncogenes (protooncogenes) have the prefix "c-" before the gene symbol. [NIH] Oogenesis: The formation, development, and maturation of the female germ cell. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Ophthalmology: A surgical specialty concerned with the structure and function of the eye and the medical and surgical treatment of its defects and diseases. [NIH] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [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] Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine. [NIH] Orofacial: Of or relating to the mouth and face. [EU] Ossification: The formation of bone or of a bony substance; the conversion of fibrous tissue or of cartilage into bone or a bony substance. [EU] Osteogenesis: The histogenesis of bone including ossification. It occurs continuously but particularly in the embryo and child and during fracture repair. [NIH]

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Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidative Phosphorylation: Electron transfer through the cytochrome system liberating free energy which is transformed into high-energy phosphate bonds. [NIH] Oxygenation: The process of supplying, treating, or mixing with oxygen. No:1245 oxygenation the process of supplying, treating, or mixing with oxygen. [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] 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] Paraffin: A mixture of solid hydrocarbons obtained from petroleum. It has a wide range of uses including as a stiffening agent in ointments, as a lubricant, and as a topical antiinflammatory. It is also commonly used as an embedding material in histology. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresthesia: Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. [NIH] Pathogen: Any disease-producing microorganism. [EU] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] 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] Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Penicillamine: 3-Mercapto-D-valine. The most characteristic degradation product of the penicillin antibiotics. It is used as an antirheumatic and as a chelating agent in Wilson's disease. [NIH]

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Penicillin: An antibiotic drug used to treat infection. [NIH] Pepsin: An enzyme made in the stomach that breaks down proteins. [NIH] Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice. [NIH] Peptic: Pertaining to pepsin or to digestion; related to the action of gastric juices. [EU] Peptic Ulcer: Ulcer that occurs in those portions of the alimentary tract which come into contact with gastric juice containing pepsin and acid. It occurs when the amount of acid and pepsin is sufficient to overcome the gastric mucosal barrier. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peripheral Nervous System Diseases: Diseases of the peripheral nerves external to the brain and spinal cord, which includes diseases of the nerve roots, ganglia, plexi, autonomic nerves, sensory nerves, and motor nerves. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] Petroleum: Naturally occurring complex liquid hydrocarbons which, after distillation, yield combustible fuels, petrochemicals, and lubricants. [NIH] Phallic: Pertaining to the phallus, or penis. [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] 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] Phosphorylase: An enzyme of the transferase class that catalyzes the phosphorylysis of a terminal alpha-1,4-glycosidic bond at the non-reducing end of a glycogen molecule, releasing a glucose 1-phosphate residue. Phosphorylase should be qualified by the natural substance acted upon. EC 2.4.1.1. [NIH] Photoreceptor: Receptor capable of being activated by light stimuli, as a rod or cone cell of the eye. [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.

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[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] Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasmid: An autonomously replicating, extra-chromosomal DNA molecule found in many bacteria. Plasmids are widely used as carriers of cloned genes. [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] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

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

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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] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [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] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] 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] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed

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and unexposed groups. [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 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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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 of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogenes: Normal cellular genes homologous to viral oncogenes. The products of proto-oncogenes are important regulators of biological processes and appear to be involved in the events that serve to maintain the ordered procession through the cell cycle. Protooncogenes have names of the form c-onc. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [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] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

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Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quiescent: Marked by a state of inactivity or repose. [EU] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] 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] 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] Reactive Oxygen Species: Reactive intermediate oxygen species including both radicals and non-radicals. These substances are constantly formed in the human body and have been shown to kill bacteria and inactivate proteins, and have been implicated in a number of diseases. Scientific data exist that link the reactive oxygen species produced by inflammatory phagocytes to cancer development. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Recombination: The formation of new combinations of genes as a result of segregation in crosses between genetically different parents; also the rearrangement of linked genes due to crossing-over. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Regeneration: The natural renewal of a structure, as of a lost tissue or part. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH]

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Respiratory failure: Inability of the lungs to conduct gas exchange. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinitis: Inflammation of the retina. It is rarely limited to the retina, but is commonly associated with diseases of the choroid (chorioretinitis) and of the optic nerve (neuroretinitis). The disease may be confined to one eye, but since it is generally dependent on a constitutional factor, it is almost always bilateral. It may be acute in course, but as a rule it lasts many weeks or even several months. [NIH] Retinitis Pigmentosa: Hereditary, progressive degeneration of the neuroepithelium of the retina characterized by night blindness and progressive contraction of the visual field. [NIH] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Retrospective: Looking back at events that have already taken place. [NIH] Retroviral vector: RNA from a virus that is used to insert genetic material into cells. [NIH] Reversion: A return to the original condition, e. g. the reappearance of the normal or wild type in previously mutated cells, tissues, or organisms. [NIH] Rhabdomyosarcoma: A malignant tumor of muscle tissue. [NIH] Rhodopsin: A photoreceptor protein found in retinal rods. It is a complex formed by the binding of retinal, the oxidized form of retinol, to the protein opsin and undergoes a series of complex reactions in response to visible light resulting in the transmission of nerve impulses to the brain. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rod: A reception for vision, located in the retina. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each

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consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Sarcomere: The repeating structural unit of a striated muscle fiber. [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] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Scoliosis: A lateral curvature of the spine. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secondary tumor: Cancer that has spread from the organ in which it first appeared to another organ. For example, breast cancer cells may spread (metastasize) to the lungs and cause the growth of a new tumor. When this happens, the disease is called metastatic breast cancer, and the tumor in the lungs is called a secondary tumor. Also called secondary cancer. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] 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] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [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 Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information. [NIH] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] 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

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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] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] 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]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solid tumor: Cancer of body tissues other than blood, bone marrow, or the lymphatic system. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the

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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] 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] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specific immune cells: Immune cells such as T and B lymphocytes that respond to a single, specific antigen. [NIH] 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] Spectrin: A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane. [NIH]

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] Spermatogenesis: Process of formation and development of spermatozoa, including spermatocytogenesis and spermiogenesis. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spirometry: Measurement of volume of air inhaled or exhaled by the lung. [NIH] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Stabilization: The creation of a stable state. [EU] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] 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

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hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

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] 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] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] 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] 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] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [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

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homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Systemic: Affecting the entire body. [NIH] Systemic disease: Disease that affects the whole body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Terminator: A DNA sequence sited at the end of a transcriptional unit that signals the end of transcription. [NIH] Tetrodotoxin: Octahydro-12-(hydroxymethyl)-2-imino-5,9:7,10a-dimethano10aH(1,3)dioxocino(6,5-a)pyrimidine-4,7,10,11,12-pentol. An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order Tetradontiformes (pufferfish, globefish, toadfish), which are eaten. The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. [NIH] Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]

Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH]

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Tidal Volume: The volume of air inspired or expired during each normal, quiet respiratory cycle. Common abbreviations are TV or V with subscript T. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Topical: On the surface of the body. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transaminases: A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1. [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] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] 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,

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between individuals of the same species, or between individuals of different species. [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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH] Ureters: Tubes that carry urine from the kidneys to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] 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, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] 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

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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] Ventilator: A breathing machine that is used to treat respiratory failure by promoting ventilation; also called a respirator. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vimentin: An intermediate filament protein found in most differentiating cells, in cells grown in tissue culture, and in certain fully differentiated cells. Its insolubility suggests that it serves a structural function in the cytoplasm. MW 52,000. [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] Virion: The infective system of a virus, composed of the viral genome, a protein core, and a protein coat called a capsid, which may be naked or enclosed in a lipoprotein envelope called the peplos. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [NIH] Vitreous: Glasslike or hyaline; often used alone to designate the vitreous body of the eye (corpus vitreum). [EU] Vitreous Body: The transparent, semigelatinous substance that fills the cavity behind the crystalline lens of the eye and in front of the retina. It is contained in a thin hyoid membrane and forms about four fifths of the optic globe. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH]

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Wheelchairs: Chairs mounted on wheels and designed to be propelled by the occupant. [NIH]

White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Wound Healing: Restoration of integrity to traumatized tissue. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]

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INDEX A Acceptor, 143, 176, 188 Acetylcholine, 21, 54, 143, 144, 152, 174 Acetylcholinesterase, 21, 143 Actin, 6, 102, 143, 172, 173, 189 Actinin, 143, 158 Adaptability, 143, 151 Adaptation, 18, 143, 174, 178 Adenine, 143 Adenosine, 48, 143, 177, 187 Adenosine Deaminase, 48, 143 Adenovirus, 5, 143 Adipose Tissue, 104, 143 Adjustment, 65, 86, 143 Adolescence, 11, 104, 144 Adverse Effect, 95, 144, 184 Aerobic, 144, 171 Affinity, 10, 144, 147 Age Groups, 10, 144 Aged, 80 and Over, 144 Agrin, 21, 144 Air Embolism, 45, 144 Air Sacs, 144, 145 Airway, 31, 58, 144 Algorithms, 144, 149 Alimentary, 144, 176, 177 Alkaline, 144, 145, 150 Alkaloid, 144, 147, 153, 187 Allogeneic, 104, 144 Alternative medicine, 114, 144 Alternative Splicing, 21, 144, 180 Alveoli, 145, 190 Amine, 145, 165 Amino Acid Sequence, 101, 145, 146, 155, 160 Ammonia, 143, 145, 163, 189 Amnion, 145 Amniotic Fluid, 27, 39, 145 Amphetamine, 145, 170 Amplification, 15, 27, 145 Anaesthesia, 30, 31, 52, 87, 145, 166 Anal, 145, 161, 169 Analogous, 17, 145, 188 Anaphylatoxins, 145, 154 Anesthesia, 45, 58, 144, 145 Angiogenesis, 18, 146 Animal model, 5, 6, 10, 11, 14, 15, 18, 24, 25, 79, 107, 108, 146

Ankle, 56, 146 Annealing, 146, 178 Antagonism, 146, 187 Anterior Cerebral Artery, 146, 152 Antibiotic, 95, 107, 146, 177 Antibodies, 101, 146, 164, 170, 172, 178 Antibody, 101, 144, 146, 154, 164, 165, 166, 171, 172, 185 Anticoagulant, 146, 180 Antigen, 43, 101, 144, 146, 154, 165, 166, 170, 185 Antigen-Antibody Complex, 146, 154 Anti-inflammatory, 146, 156, 163, 176, 179 Antiserum, 102, 146 Aorta, 146, 166, 179, 190 Apoptosis, 67, 146 Applicability, 25, 147 Aqueous, 147, 148, 156, 159 Arginine, 145, 147, 174, 175 Arrhythmia, 72, 147 Arterial, 9, 147, 152, 180, 187 Arteries, 146, 147, 149, 155, 166, 171 Arterioles, 147, 149, 189 Artery, 5, 33, 146, 147, 155, 161, 180, 183, 188 Assay, 26, 147 Astrocytes, 147, 164 Astrocytoma, 147, 163 Atrioventricular, 19, 147 Atrium, 147, 190 Atrophy, 79, 147, 169, 174 Atropine, 103, 147, 148 Auditory, 147, 160 Autoimmune disease, 147, 172 Autologous, 104, 147 Autonomic, 54, 103, 143, 147, 148, 177, 184, 186 Autonomic Nervous System, 103, 147, 148, 177, 184, 186 B Bacteria, 146, 148, 149, 160, 162, 164, 169, 170, 171, 178, 181, 188, 189 Bacterial Physiology, 143, 148 Bacteriophage, 148, 188 Baroreflex, 103, 148 Basal Ganglia, 148, 163, 173 Base, 61, 102, 107, 143, 148, 157, 161, 168, 178, 187

194

Duchenne Muscular Dystrophy

Base Sequence, 148, 161 Basement Membrane, 148, 160, 168 Belladonna, 147, 148 Bilateral, 148, 182 Bile, 148, 162, 169, 185 Biochemical, 10, 19, 21, 22, 41, 48, 51, 55, 73, 77, 84, 91, 148 Bioengineering, 6, 120, 148 Biogenesis, 22, 148 Bioluminescence, 59, 148, 169 Biopsy, 45, 54, 64, 140, 149 Biotechnology, 26, 29, 114, 121, 149 Bladder, 33, 149, 162, 172, 189 Blood Coagulation, 149, 150, 187 Blood pressure, 148, 149, 172 Blood vessel, 11, 146, 148, 149, 152, 153, 159, 168, 184, 186, 187, 188, 189 Body Composition, 64, 149 Bone Marrow, 28, 57, 104, 149, 162, 170, 172, 184 Bone Marrow Transplantation, 28, 57, 104, 149 Bowel, 145, 149, 157 Bowel Movement, 149, 157 Bradykinin, 149, 174 Branch, 137, 149, 156, 158, 176, 185, 187 Breakdown, 62, 78, 104, 149, 157, 162, 175 Bronchi, 149, 187 Bronchial, 107, 149, 165, 187 Buffers, 148, 149, 185 C Calcium, 10, 35, 52, 59, 61, 76, 77, 78, 149, 150, 154, 184, 189 Calpain, 64, 150 Capping, 33, 150 Capsid, 150, 190 Carbohydrate, 150, 155, 163, 179, 183 Carbon Dioxide, 150, 157, 161, 162, 181, 189 Carcinogenic, 150, 179, 185 Cardiac, 8, 17, 19, 32, 36, 37, 52, 54, 77, 103, 104, 105, 148, 150, 157, 162, 173, 183, 185 Cardiac arrest, 52, 150 Cardiac Output, 148, 150 Cardiomyopathy, 17, 19, 30, 76, 150 Cardiomyoplasty, 17, 150 Cardiopulmonary, 13, 150 Carnitine, 76, 78, 150 Carotene, 150, 182 Case report, 29, 69, 150 Catabolism, 20, 150 Catecholamines, 150, 158, 170

Caudal, 151, 165, 179 Caveolae, 55, 151 Caveolins, 151 Cell Adhesion, 9, 151 Cell Adhesion Molecules, 9, 151 Cell Death, 146, 151 Cell Differentiation, 13, 19, 151, 184 Cell Lineage, 11, 151 Cell membrane, 25, 38, 102, 107, 151 Cell Membrane Structures, 151 Cell proliferation, 151, 175, 184 Cell Respiration, 151, 171, 181 Cell Survival, 17, 151, 164 Cell Transplantation, 17, 32, 45, 82, 84, 151 Central Nervous System, 7, 56, 143, 145, 148, 151, 153, 158, 160, 162, 163, 172, 175, 187 Cerebral, 47, 54, 55, 68, 146, 148, 151, 152, 160, 162, 163, 187 Cerebral Cortex, 47, 151, 160 Cerebral hemispheres, 148, 151, 152, 163, 187 Cerebral Infarction, 54, 152 Cerebrum, 151, 152, 187 Cervix, 152, 161 Character, 152, 157 Chemokines, 9, 152 Chemotactic Factors, 152, 154 Chimeric Proteins, 21, 152 Chin, 152, 171 Cholesterol, 148, 151, 152, 169, 185 Choline, 55, 143, 152 Cholinergic, 46, 152 Chondrocytes, 152, 161 Chondroitin sulfate, 76, 152 Chorioretinitis, 152, 182 Choroid, 152, 182 Chromatin, 19, 147, 152, 159 Chromosomal, 145, 152, 178, 183, 187 Chromosome, 16, 28, 51, 69, 72, 73, 100, 101, 102, 105, 106, 107, 153, 169, 183, 187 Chronic, 23, 103, 153, 157, 167, 186 Chronic Disease, 23, 153 Circulatory system, 144, 153 CIS, 9, 153, 182 Clear cell carcinoma, 153, 157 Cleave, 150, 153 Clinical Medicine, 77, 153, 179 Clinical trial, 4, 8, 11, 12, 14, 24, 32, 37, 93, 95, 96, 121, 153, 158, 181 Clone, 29, 153 Cloning, 14, 149, 153

Index

Cocaine, 153, 170 Codon, 12, 25, 107, 153 Cognition, 153, 168 Collagen, 145, 148, 153, 161, 178 Collapse, 149, 153 Colloidal, 154, 158 Complement, 22, 82, 145, 154, 163 Complementary and alternative medicine, 81, 89, 154 Complementary medicine, 81, 154 Complementation, 5, 154 Computational Biology, 121, 154 Concentric, 154, 174 Concomitant, 6, 77, 84, 154 Conduction, 19, 54, 126, 154, 187 Cone, 154, 177 Congestive heart failure, 17, 154 Connective Tissue, 149, 153, 155, 161, 162, 180 Consensus Sequence, 155 Conserved Sequence, 27, 28, 155 Constitutional, 155, 182 Constriction, 155, 168, 183 Contamination, 5, 155 Continuum, 6, 8, 155 Contractility, 13, 155 Contracture, 34, 155 Contraindications, ii, 155 Coordination, 140, 155, 172 Corneum, 155, 159, 165 Coronary, 155, 171 Coronary Thrombosis, 155, 171 Corpuscle, 155, 160 Cortex, 155, 160, 179 Corticosteroid, 77, 155, 179 Cortisone, 156, 179 Creatine, 38, 59, 61, 78, 80, 81, 82, 83, 86, 94, 95, 126, 156 Creatine Kinase, 59, 81, 126, 156 Creatinine, 156 Crossing-over, 156, 181 Cultured cells, 52, 156 Curative, 12, 156, 187 Cyclic, 20, 150, 156, 164, 174, 187 Cytochrome, 156, 176 Cytogenetics, 156, 183 Cytokine, 9, 156 Cytoplasm, 147, 151, 156, 159, 164, 167, 172, 173, 174, 182, 190 Cytoskeleton, 6, 22, 51, 103, 156 Cytotoxic, 18, 25, 156, 184

195

D Data Collection, 23, 156 De novo, 38, 102, 105, 157 Decarboxylation, 157, 165 Degenerative, 4, 9, 20, 22, 103, 105, 157 Deletion, 16, 24, 27, 38, 39, 48, 60, 61, 63, 68, 100, 101, 104, 107, 147, 157, 162 Denaturation, 157, 178 Dendrites, 157, 174 Density, 27, 34, 157, 169, 175, 185 Deprivation, 29, 84, 157 DES, 77, 145, 157 Desmin, 157, 167 Diagnostic procedure, 99, 114, 157 Diaphragm, 9, 11, 39, 157 Digestion, 144, 148, 149, 157, 169, 177, 186 Digestive system, 97, 157 Dilated cardiomyopathy, 73, 157 Diploid, 154, 157, 178 Direct, iii, 24, 26, 27, 39, 40, 108, 153, 157, 158, 169, 181, 186 Disease Progression, 95, 157 Dislocation, 50, 157 Dissection, 6, 157 Dissociation, 144, 157 Distal, 102, 127, 158, 180 Diuresis, 158, 187 Dopamine, 145, 153, 158, 170, 174 Dorsal, 158, 179 Double-blind, 94, 158 Dystrophic, 5, 6, 10, 11, 13, 17, 18, 22, 25, 28, 158 E Effector, 143, 154, 158 Efferent, 158, 172 Efficacy, 8, 15, 45, 84, 93, 94, 158 Elastic, 59, 158, 185, 188 Electrophoresis, 39, 43, 101, 158 Electrophysiological, 158, 190 Elementary Particles, 158, 170, 180 Embryo, 145, 151, 159, 161, 166, 175 Emollient, 159, 163, 175 Emulsion, 159, 161 Endemic, 159, 185 Endocytosis, 151, 159 Endogenous, 108, 150, 158, 159, 188 Endothelial cell, 9, 159, 161, 187 Endothelium, 159, 174 Endothelium-derived, 159, 174 Endotoxins, 154, 159, 168 Energy Intake, 78, 159 Enhancer, 61, 100, 106, 159

196

Duchenne Muscular Dystrophy

Environmental Health, 120, 122, 159 Enzymatic, 19, 145, 150, 154, 159, 165, 178, 182 Enzyme, 143, 158, 159, 162, 163, 164, 168, 169, 177, 178, 180, 184, 186, 187, 190, 191 Eosinophils, 18, 159, 164, 168 Epidemic, 159, 185 Epidemiological, 30, 159 Epidermis, 155, 159, 165 Epithelial, 107, 160, 168 Epithelial Cells, 160, 168 Erythrocyte Membrane, 85, 160, 185 Erythrocytes, 82, 88, 149, 150, 160, 164 Escalation, 11, 160 Esophagus, 157, 160, 186 Evoke, 160, 186 Evoked Potentials, 68, 160 Excitation, 10, 160, 174 Exogenous, 17, 159, 160 Exon, 5, 19, 27, 37, 100, 105, 106, 144, 160 Extracellular, 6, 22, 83, 147, 155, 159, 160, 161 Extracellular Matrix, 6, 22, 83, 155, 160, 161 Extracellular Space, 160 Extravasation, 9, 160 Extremity, 62, 70, 160 Eye Infections, 143, 160 F Facial, 4, 16, 160, 184 Family Planning, 121, 160 Fasciculation, 160, 174 Fat, 143, 149, 150, 155, 160, 169, 172, 184 Fatigue, 140, 160, 164 Femoral, 12, 161 Femoral Artery, 12, 161 Femur, 161 Fetal Alcohol Syndrome, 110, 161 Fetal Development, 103, 161 Fetus, 161, 179, 189 Fibroblast Growth Factor, 43, 161 Fibroblasts, 46, 55, 161 Fibrosis, 18, 22, 27, 40, 107, 114, 155, 161, 183 Fine-needle aspiration, 161, 173 Fixation, 62, 161 Flexion, 59, 161 Fluorescence, 19, 161 Fovea, 161 Frameshift, 12, 26, 46, 161, 162 Frameshift Mutation, 12, 26, 162 Frontal Lobe, 146, 152, 162

Fundus, 161, 162 Fungi, 149, 160, 162, 171, 189, 191 G Gait, 47, 71, 95, 162 Gallbladder, 157, 162 Ganglia, 143, 162, 174, 177, 186 Gas, 145, 150, 162, 165, 167, 174, 182, 189, 190 Gas exchange, 162, 182, 189, 190 Gastric, 150, 162, 165, 177 Gastric Juices, 162, 177 Gastric Mucosa, 162, 177 Gastrin, 162, 165 Gene Deletion, 26, 37, 41, 66, 162 Gene Expression, 5, 8, 9, 12, 14, 16, 20, 53, 102, 162 Gene Therapy, 6, 7, 8, 11, 14, 24, 31, 44, 53, 58, 63, 66, 68, 95, 143, 162 Genetic Engineering, 149, 153, 163 Genetic testing, 163, 179 Genomics, 11, 100, 106, 163 Genotype, 7, 26, 49, 63, 163, 177 Gland, 156, 163, 176, 178, 183, 186 Glioblastoma, 105, 163 Glucocorticoid, 39, 83, 163, 179 Glucose, 14, 31, 50, 77, 163, 164, 167, 177, 183 Glutamic Acid, 163, 174 Glutamine, 55, 62, 78, 94, 95, 163 Glutathione Peroxidase, 163, 183 Glycerol, 37, 163 Glycerol Kinase, 37, 163 Glycine, 145, 163, 174 Glycoprotein, 10, 12, 163, 168, 187 Glycosaminoglycan, 152, 164 Gonadal, 164, 185 Governing Board, 164, 179 Graft, 9, 164, 165 Graft Survival, 9, 164 Grafting, 164, 166 Granulocytes, 164, 173, 184, 191 Growth factors, 164, 175 Guanylate Cyclase, 164, 174 H Haptens, 144, 164 Heart failure, 30, 31, 164 Hematopoietic Stem Cells, 104, 164 Hemoglobin, 160, 164 Hemoglobinopathies, 163, 164 Hemolysis, 160, 164 Hemorrhage, 69, 164, 186 Heparan Sulfate Proteoglycan, 33, 164

Index

Hereditary, 100, 101, 105, 106, 128, 164, 182 Heredity, 162, 163, 164 Heterogeneity, 13, 22, 49, 144, 165 Histamine, 24, 145, 165 Histidine, 165 Histology, 9, 20, 25, 165, 176 Homeostasis, 13, 76, 165, 184 Homogenate, 101, 165 Homogeneous, 155, 165 Homologous, 29, 156, 162, 165, 180, 183, 187 Hormonal, 147, 156, 165 Hormone, 33, 77, 79, 96, 155, 156, 157, 162, 165, 167, 171, 179, 184 Host, 14, 18, 82, 148, 164, 165, 190 Hybrid, 87, 153, 165 Hybridization, 22, 165 Hydrogen, 143, 145, 148, 149, 150, 157, 163, 165, 172, 175, 176, 180 Hydrolysis, 143, 165, 180 Hydroxyproline, 145, 153, 165 Hypertrophy, 11, 20, 165 Hypothalamus, 148, 165, 178 I Ichthyosis, 41, 165, 166 Ichthyosis Vulgaris, 41, 166 Id, 80, 88, 129, 136, 138, 166 Iliac Artery, 161, 166 Immune response, 14, 18, 24, 53, 146, 147, 156, 164, 166, 186, 190 Immune system, 9, 18, 24, 166, 170, 172, 173, 191 Immunity, 24, 166 Immunoglobulin, 146, 166, 172 Immunology, 8, 82, 144, 166 Immunosuppressive, 163, 166 Impairment, 54, 160, 166, 171 Implantation, 17, 166 In situ, 23, 54, 166 In vitro, 7, 9, 23, 26, 52, 55, 76, 77, 162, 166, 178 In vivo, 5, 14, 17, 20, 26, 108, 162, 166 Incision, 166, 167 Incubated, 107, 166 Incubation, 107, 166 Indicative, 110, 166, 176, 189 Induction, 5, 19, 26, 166 Infancy, 100, 106, 166 Infant, Newborn, 144, 166 Infarction, 152, 155, 166, 171

197

Infection, 5, 9, 152, 160, 166, 170, 177, 186, 191 Inflammation, 146, 152, 160, 161, 167, 174, 178, 182 Ingestion, 79, 167 Inlay, 167, 182 Innervation, 14, 167 Inorganic, 167, 169 Insight, 15, 167 Insufflation, 85, 167 Insulator, 167, 172 Insulin, 14, 96, 105, 167 Insulin-dependent diabetes mellitus, 167 Insulin-like, 96, 105, 167 Intermediate Filament Proteins, 19, 167 Intermittent, 65, 167 Intracellular, 10, 83, 166, 167, 171, 174, 183, 184 Intramuscular, 5, 167, 176 Intraperitoneal, 77, 167 Intravascular, 12, 167 Intravenous, 12, 167, 176 Intrinsic, 26, 144, 148, 167 Introns, 21, 38, 167 Invasive, 6, 103, 166, 167, 170 Invertebrates, 168, 170 Involuntary, 168, 173, 185 Ions, 148, 149, 157, 165, 168 Ischemia, 27, 47, 147, 168 Isoenzyme, 156, 168 Isolated limb perfusion, 24, 168 J Joint, 43, 59, 168, 170 K Kb, 14, 100, 102, 106, 120, 168 Keto, 168, 188 Kinetics, 39, 168 L Labile, 154, 168 Lacrimal, 168, 175 Laminin, 6, 13, 148, 168 Language Development, 7, 104, 168 Large Intestine, 157, 168, 181, 184 Lethal, 18, 22, 24, 25, 104, 168 Leukemia, 41, 163, 168 Leukocytes, 149, 152, 159, 164, 168, 172 Library Services, 136, 168 Life Expectancy, 68, 168 Ligands, 151, 168 Limb perfusion, 168 Linkage, 28, 73, 150, 169 Lipid, 151, 152, 163, 167, 168, 169, 172

198

Duchenne Muscular Dystrophy

Lipodystrophy, 20, 169 Lipoprotein, 169, 190 Liver, 148, 150, 157, 159, 162, 169, 179, 187, 189 Lobe, 146, 152, 169 Localization, 8, 33, 44, 59, 96, 169 Localized, 10, 13, 102, 157, 158, 161, 166, 168, 169, 178 Locomotion, 42, 169, 178 Locomotor, 32, 82, 104, 169 Longitudinal study, 7, 56, 62, 169 Loop, 7, 169 Lucida, 168, 169 Luciferase, 26, 169 Lumbar, 62, 169 Luminescence, 43, 169 Luxation, 157, 170 Lymph, 153, 155, 159, 170 Lymphatic, 159, 167, 170, 184 Lymphocyte, 33, 146, 170, 171 Lymphoid, 18, 146, 170 M Magnetic Resonance Imaging, 34, 65, 67, 170 Magnetic Resonance Spectroscopy, 35, 61, 78, 86, 170 Malignant, 41, 163, 170, 182 Malignant tumor, 170, 182 Malnutrition, 63, 147, 170, 173 Mandible, 4, 152, 170 Manifest, 4, 5, 170 Masseter Muscle, 4, 170 Mastication, 170 Masticatory, 3, 170 Maxillary, 4, 170 Mazindol, 77, 79, 170 Mechanical ventilation, 55, 170 Mediate, 13, 151, 158, 170 Mediator, 20, 170 Medicament, 100, 171 MEDLINE, 121, 171 Membrane Proteins, 151, 171 Memory, 7, 92, 171 Meninges, 151, 171 Mental, iv, 4, 37, 97, 104, 120, 122, 151, 152, 153, 157, 160, 161, 171, 180 Mental deficiency, 161, 171 Mental Disorders, 97, 171, 180 Mental Retardation, 37, 171 Metastasis, 22, 151, 171 Metastatic, 77, 84, 171, 183 MI, 141, 171

Microbe, 171, 188 Microbiology, 143, 171 Microorganism, 171, 176, 190 Microscopy, 8, 19, 148, 171 Midwifery, 109, 171 Migration, 9, 171 Mitochondria, 76, 171 Mitosis, 147, 171 Mobility, 19, 172 Modification, 145, 163, 172, 181 Modulator, 20, 172 Monitor, 42, 95, 156, 172, 174 Monoclonal, 15, 172 Monoclonal antibodies, 15, 172 Monocytes, 168, 172, 173 Morphogenesis, 161, 172 Morphological, 21, 33, 159, 172 Morphology, 3, 25, 35, 172 Motor nerve, 13, 160, 172, 177 Motor Neurons, 52, 172 Motor Skills, 56, 172 Multiple sclerosis, 51, 172 Muscle Contraction, 103, 158, 172 Muscle Fibers, 10, 19, 22, 44, 59, 65, 103, 104, 107, 144, 172, 173, 189 Muscle Hypertonia, 172, 174 Muscle Proteins, 10, 20, 104, 173 Muscular Atrophy, 34, 55, 58, 62, 65, 100, 106, 126, 173 Muscular Dystrophies, 5, 6, 11, 87, 104, 127, 128, 158, 173 Musculature, 4, 173 Mutagens, 162, 173 Myelin, 172, 173 Myeloid Cells, 18, 173 Myocardium, 17, 70, 171, 173 Myofibrils, 22, 150, 158, 173 Myopathy, 19, 173 Myosin, 18, 41, 172, 173, 189 Myotonic Dystrophy, 3, 16, 52, 173 N Naive, 94, 173 Natural selection, 148, 173 NCI, 1, 96, 119, 153, 173 Need, 3, 8, 26, 55, 109, 111, 130, 144, 173 Needle biopsy, 95, 161, 173 Neonatal, 14, 59, 60, 173 Neoplastic, 173, 175 Nervous System, 104, 145, 147, 151, 170, 173, 174, 177, 186 Neurologic, 14, 163, 174 Neuromuscular Diseases, 86, 174

Index

Neuromuscular Junction, 13, 21, 143, 174 Neuronal, 14, 27, 44, 47, 174 Neurons, 52, 153, 157, 162, 172, 174, 186 Neuropeptides, 150, 174 Neuroretinitis, 174, 182 Neurotransmitter, 143, 145, 149, 158, 163, 165, 174, 184, 186 Night Blindness, 174, 182 Nitric Oxide, 13, 18, 27, 31, 44, 47, 174 Nitrogen, 144, 145, 161, 163, 174 Nuclear, 19, 30, 148, 163, 174, 175 Nuclear Envelope, 19, 174 Nuclear Pore, 174 Nuclei, 28, 57, 146, 162, 163, 167, 170, 171, 174, 175, 180 Nucleic acid, 148, 150, 165, 173, 174, 175 Nucleic Acid Hybridization, 165, 175 Nucleus, 146, 147, 152, 156, 158, 159, 172, 174, 175, 180, 184, 186 O Occupational Therapy, 111, 175 Ointments, 175, 176 Oncogenes, 105, 175, 180 Oogenesis, 61, 175 Opacity, 157, 175 Operon, 175, 181 Ophthalmology, 161, 175 Opsin, 175, 182 Optic Nerve, 174, 175, 182 Orbicularis, 4, 175 Ornithine, 48, 51, 175 Orofacial, 3, 175 Ossification, 175 Osteogenesis, 110, 175 Ovaries, 176, 184, 187 Oxidation, 77, 143, 156, 163, 176 Oxidative Phosphorylation, 76, 176 Oxygenation, 60, 176 P Palate, 4, 176 Palliative, 176, 187 Pancreas, 157, 167, 176 Pancreatic, 150, 176 Paraffin, 53, 77, 176 Paralysis, 176, 187 Parenteral, 159, 176 Paresthesia, 176, 187 Pathogen, 166, 176 Pathogenesis, 16, 176 Pathologic, 20, 108, 147, 149, 155, 176 Pathologic Processes, 147, 176 Pathologies, 13, 176

199

Pathologist, 176 Pathophysiology, 16, 176 Pelvis, 166, 169, 176, 189 Penicillamine, 76, 176 Penicillin, 146, 176, 177, 189 Pepsin, 177 Pepsin A, 177 Peptic, 29, 177 Peptic Ulcer, 29, 177 Peptide, 145, 161, 177, 180 Perception, 19, 87, 154, 177 Peripheral Nervous System, 174, 177, 186 Peripheral Nervous System Diseases, 174, 177 Peritoneal, 167, 177 Peritoneal Cavity, 167, 177 Petroleum, 176, 177 Phallic, 161, 177 Pharmacologic, 145, 177, 188 Phenotype, 5, 6, 7, 8, 21, 24, 26, 43, 77, 104, 105, 154, 162, 177 Phosphorus, 35, 150, 177 Phosphorylase, 150, 177 Photoreceptor, 7, 177, 182 Physical Therapy, 64, 86, 111, 126, 177 Physiologic, 161, 178, 181 Physiology, 6, 10, 13, 16, 21, 35, 55, 59, 76, 78, 158, 178 Pigments, 150, 178, 182 Pilot study, 68, 93, 94, 178 Pituitary Gland, 155, 161, 178 Plants, 144, 147, 148, 150, 152, 153, 163, 172, 178, 182, 188 Plasma, 22, 46, 65, 76, 103, 146, 151, 158, 164, 178, 183 Plasma cells, 146, 178 Plasmid, 11, 178, 189 Plasticity, 12, 178 Platelet Aggregation, 145, 174, 178 Platelets, 150, 174, 178 Platinum, 169, 178 Pneumonia, 155, 178 Point Mutation, 25, 39, 45, 53, 61, 107, 178 Polymerase, 48, 66, 178, 181 Polymerase Chain Reaction, 48, 66, 178 Polymorphic, 39, 152, 179 Polysaccharide, 146, 164, 179, 180 Posterior, 4, 145, 152, 158, 175, 176, 179 Postnatal, 161, 179, 185 Postsynaptic, 14, 21, 27, 179, 184 Post-synaptic, 14, 179 Practice Guidelines, 122, 179

200

Duchenne Muscular Dystrophy

Preclinical, 30, 69, 179 Precursor, 9, 21, 152, 158, 159, 179, 189 Prednisolone, 63, 65, 78, 179 Prednisone, 42, 50, 58, 95, 96, 179 Prenatal, 27, 36, 39, 45, 48, 54, 63, 70, 104, 159, 161, 179 Pressoreceptors, 148, 179 Presynaptic, 13, 174, 179 Prevalence, 3, 33, 46, 68, 72, 179 Progesterone, 179, 185 Progression, 10, 16, 18, 36, 38, 43, 79, 106, 146, 179 Progressive, 7, 13, 15, 17, 19, 22, 23, 100, 102, 104, 107, 111, 151, 160, 164, 173, 179, 182 Promoter, 5, 27, 29, 101, 106, 179 Prone, 27, 179 Prophylaxis, 76, 86, 179 Prospective study, 64, 169, 179 Protein C, 71, 103, 107, 144, 145, 148, 153, 169, 173, 180, 185, 189, 190 Protein Conformation, 145, 180 Protein Isoforms, 144, 180 Protein Kinases, 175, 180 Protein S, 149, 155, 180, 182 Proteoglycan, 76, 180 Proteolytic, 154, 180 Protons, 165, 170, 180, 181 Proto-Oncogenes, 175, 180 Protozoa, 149, 171, 180, 189 Proximal, 158, 179, 180 Psychiatry, 52, 56, 79, 161, 180, 190 Psychic, 171, 180, 183 Public Policy, 121, 180 Pulmonary, 38, 52, 86, 149, 180, 189, 190 Pulmonary Artery, 149, 180, 190 Pulse, 172, 180 Q Quality of Life, 6, 25, 72, 104, 181 Quiescent, 5, 181 R Race, 171, 181 Radiation, 159, 161, 181, 191 Radioactive, 165, 166, 172, 174, 181 Randomized, 12, 94, 95, 158, 181 Reactive Oxygen Species, 85, 181 Reagent, 169, 181 Receptor, 143, 146, 154, 158, 160, 177, 181, 184 Recombinant, 5, 6, 8, 24, 181, 189 Recombination, 51, 162, 181 Rectum, 149, 157, 162, 168, 181

Recurrence, 49, 181 Refer, 1, 154, 161, 162, 169, 173, 175, 181, 188 Regeneration, 10, 18, 20, 104, 144, 161, 181 Regimen, 158, 181 Remission, 65, 181 Repressor, 22, 175, 181 Respiration, 150, 172, 181 Respirator, 170, 181, 190 Respiratory failure, 104, 182, 190 Respiratory Physiology, 40, 85, 182, 189 Restoration, 77, 87, 177, 182, 191 Retina, 6, 152, 174, 175, 182, 190 Retinal, 6, 154, 175, 182 Retinitis, 52, 182 Retinitis Pigmentosa, 52, 182 Retinol, 182 Retrospective, 100, 106, 182 Retroviral vector, 66, 162, 182 Reversion, 108, 182 Rhabdomyosarcoma, 41, 77, 84, 182 Rhodopsin, 175, 182 Ribose, 143, 182 Ribosome, 182, 188 Risk factor, 179, 182 Rod, 5, 102, 177, 182 S Salivary, 157, 182 Salivary glands, 157, 182 Saponins, 182, 185 Sarcolemma, 22, 183 Sarcomere, 10, 22, 183 Satellite, 17, 24, 183 Sclerosis, 126, 172, 183 Scoliosis, 62, 127, 183 Screening, 27, 59, 60, 66, 93, 94, 153, 183 Secondary tumor, 171, 183 Secretion, 76, 79, 156, 165, 167, 183 Segregation, 181, 183 Seizures, 163, 183 Selenium, 78, 79, 87, 183 Self-Help Groups, 110, 183 Sensibility, 145, 183 Sequence Analysis, 26, 183 Sequencing, 179, 183 Serum, 12, 20, 43, 140, 145, 146, 154, 156, 183 Sex Characteristics, 144, 183 Shock, 44, 103, 184 Side effect, 144, 170, 184, 188 Signal Transduction, 151, 184 Skeleton, 143, 161, 168, 184

Index

Skull, 184, 187 Small intestine, 165, 184 Smooth muscle, 12, 34, 145, 150, 165, 172, 184, 185, 186 Social Environment, 181, 184 Soft tissue, 149, 184 Solid tumor, 146, 184 Solitary Nucleus, 148, 184 Solvent, 163, 184 Soma, 184, 185 Somatic, 24, 39, 49, 53, 144, 172, 177, 185 Sound wave, 154, 185 Spasm, 174, 185 Specialist, 130, 185 Species, 15, 19, 143, 144, 148, 151, 155, 157, 165, 171, 172, 181, 185, 186, 189, 190, 191 Specific immune cells, 18, 185 Specificity, 15, 19, 22, 26, 101, 144, 185 Spectrin, 87, 88, 158, 185 Speech pathologist, 111, 185 Sperm, 153, 185 Spermatogenesis, 61, 185 Spinal cord, 147, 151, 152, 171, 173, 177, 185, 186 Spirometry, 36, 185 Sporadic, 38, 63, 185 Stabilization, 13, 185 Stabilizer, 94, 185 Statistically significant, 16, 185 Stem Cells, 8, 11, 17, 84, 185 Steroid, 93, 94, 156, 183, 185 Stimulant, 145, 165, 186, 189 Stimulus, 46, 155, 160, 167, 186, 187 Stomach, 157, 160, 162, 165, 177, 184, 186 Strand, 178, 186 Stress, 16, 22, 30, 44, 62, 65, 84, 86, 140, 147, 186 Stroke, 14, 95, 96, 97, 120, 126, 127, 128, 150, 186 Subacute, 167, 186 Subclinical, 166, 183, 186 Subcutaneous, 169, 176, 186 Subspecies, 185, 186 Substance P, 183, 186 Substrate, 66, 78, 186 Supplementation, 61, 78, 83, 86, 87, 186 Support group, 141, 186 Suppression, 107, 156, 186 Sympathetic Nervous System, 147, 186 Symptomatic, 39, 44, 186 Synapse, 7, 13, 144, 174, 179, 186, 188 Synaptic, 144, 174, 184, 186

Systemic, 5, 9, 24, 25, 146, 149, 165, 167, 179, 187, 189 Systemic disease, 165, 187 Systolic, 63, 187 T Tachycardia, 103, 187 Telencephalon, 148, 151, 187 Telomere, 43, 187 Temporal, 18, 187 Terminator, 153, 187 Tetrodotoxin, 76, 187 Theophylline, 76, 187 Therapeutics, 6, 18, 25, 187 Thermal, 157, 178, 187 Thigh, 161, 187 Thoracic, 157, 187 Thorax, 42, 53, 169, 187 Threshold, 17, 187 Thrombin, 178, 180, 187 Thrombomodulin, 180, 187 Thrombosis, 180, 186, 187 Tidal Volume, 31, 188 Tone, 13, 172, 188 Tonus, 4, 188 Tooth Preparation, 143, 188 Topical, 176, 188 Tourniquet, 168, 169, 188 Toxic, iv, 147, 158, 166, 170, 183, 188 Toxicity, 5, 95, 188 Toxicology, 122, 188 Toxin, 34, 187, 188 Transaminases, 42, 188 Transcription Factors, 175, 188 Transduction, 5, 9, 43, 184, 188 Transfection, 26, 149, 162, 188 Translation, 15, 145, 188 Translational, 37, 188 Translocation, 50, 188 Transmitter, 13, 143, 147, 158, 170, 188 Transplantation, 17, 36, 82, 188 Tropomyosin, 173, 189 Troponin, 37, 173, 189 U Unconscious, 166, 189 Urea, 175, 189 Ureters, 189 Urethra, 189 Urinary, 43, 70, 79, 95, 189 Urinary tract, 95, 189 Urine, 95, 149, 156, 158, 189 Uterus, 152, 161, 162, 176, 179, 189

201

202

Duchenne Muscular Dystrophy

V Vaccines, 189, 190 Vagina, 152, 157, 189 Valine, 176, 189 Vascular, 9, 12, 34, 60, 148, 152, 159, 166, 167, 174, 179, 189 Vascular Resistance, 148, 189 Vasodilator, 149, 158, 165, 189 Vector, 5, 8, 9, 11, 14, 24, 102, 188, 189 Vein, 9, 95, 167, 174, 183, 189 Venom, 82, 189 Venous, 152, 180, 189 Venous blood, 152, 189 Ventilation, 41, 53, 57, 68, 69, 71, 85, 189, 190 Ventilator, 68, 72, 170, 181, 190 Ventricle, 5, 147, 165, 180, 187, 190 Ventricular, 42, 63, 72, 190 Ventricular Function, 42, 190 Venules, 149, 190 Veterinary Medicine, 121, 190 Vimentin, 167, 190 Viral, 5, 8, 14, 24, 102, 105, 150, 175, 180, 188, 190

Viral vector, 5, 14, 102, 190 Virion, 9, 190 Virulence, 188, 190 Virus, 5, 6, 8, 14, 148, 150, 159, 163, 182, 188, 190 Visceral, 148, 190 Visceral Afferents, 148, 190 Visual field, 182, 190 Vitreous, 152, 182, 190 Vitreous Body, 152, 182, 190 Vitro, 67, 190 Vivo, 5, 14, 190 W Wheelchairs, 102, 126, 191 White blood cell, 146, 166, 168, 170, 178, 191 Wound Healing, 151, 161, 191 X Xenograft, 146, 191 X-ray, 161, 174, 185, 191 Y Yeasts, 162, 177, 191 Z Zymogen, 180, 191

Index

203

204

Duchenne Muscular Dystrophy

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