DOWN
SYNDROME 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 2003 by ICON Group International, Inc. Copyright 2003 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., 1960Down Syndrome: 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: 0-597-83654-X 1. Down Syndrome-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on Down syndrome. 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 DOWN SYNDROME ................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Down Syndrome ......................................................................... 14 E-Journals: PubMed Central ....................................................................................................... 81 The National Library of Medicine: PubMed ................................................................................ 82 CHAPTER 2. NUTRITION AND DOWN SYNDROME........................................................................ 213 Overview.................................................................................................................................... 213 Finding Nutrition Studies on Down Syndrome ........................................................................ 213 Federal Resources on Nutrition ................................................................................................. 217 Additional Web Resources ......................................................................................................... 217 CHAPTER 3. ALTERNATIVE MEDICINE AND DOWN SYNDROME ................................................. 219 Overview.................................................................................................................................... 219 National Center for Complementary and Alternative Medicine................................................ 219 Additional Web Resources ......................................................................................................... 225 General References ..................................................................................................................... 226 CHAPTER 4. DISSERTATIONS ON DOWN SYNDROME ................................................................... 227 Overview.................................................................................................................................... 227 Dissertations on Down Syndrome ............................................................................................. 227 Keeping Current ........................................................................................................................ 234 CHAPTER 5. CLINICAL TRIALS AND DOWN SYNDROME .............................................................. 235 Overview.................................................................................................................................... 235 Recent Trials on Down Syndrome ............................................................................................. 235 Keeping Current on Clinical Trials ........................................................................................... 237 CHAPTER 6. PATENTS ON DOWN SYNDROME .............................................................................. 239 Overview.................................................................................................................................... 239 Patents on Down Syndrome ...................................................................................................... 239 Patent Applications on Down Syndrome .................................................................................. 248 Keeping Current ........................................................................................................................ 250 CHAPTER 7. BOOKS ON DOWN SYNDROME .................................................................................. 251 Overview.................................................................................................................................... 251 Book Summaries: Federal Agencies............................................................................................ 251 Book Summaries: Online Booksellers......................................................................................... 253 The National Library of Medicine Book Index ........................................................................... 260 Chapters on Down Syndrome .................................................................................................... 261 Directories.................................................................................................................................. 267 CHAPTER 8. MULTIMEDIA ON DOWN SYNDROME ....................................................................... 269 Overview.................................................................................................................................... 269 Video Recordings ....................................................................................................................... 269 Bibliography: Multimedia on Down Syndrome......................................................................... 270 CHAPTER 9. PERIODICALS AND NEWS ON DOWN SYNDROME .................................................... 271 Overview.................................................................................................................................... 271 News Services and Press Releases.............................................................................................. 271 Newsletters on Down Syndrome ............................................................................................... 277 Newsletter Articles .................................................................................................................... 278 Academic Periodicals covering Down Syndrome....................................................................... 279 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 283 Overview.................................................................................................................................... 283 NIH Guidelines.......................................................................................................................... 283 NIH Databases........................................................................................................................... 285
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Other Commercial Databases..................................................................................................... 288 The Genome Project and Down Syndrome ................................................................................ 288 APPENDIX B. PATIENT RESOURCES ............................................................................................... 293 Overview.................................................................................................................................... 293 Patient Guideline Sources.......................................................................................................... 293 Associations and Down Syndrome ............................................................................................ 302 Finding Associations.................................................................................................................. 312 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 315 Overview.................................................................................................................................... 315 Preparation................................................................................................................................. 315 Finding a Local Medical Library................................................................................................ 315 Medical Libraries in the U.S. and Canada ................................................................................. 315 ONLINE GLOSSARIES................................................................................................................ 321 Online Dictionary Directories ................................................................................................... 323 DOWN SYNDROME DICTIONARY ........................................................................................ 325 INDEX .............................................................................................................................................. 407
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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 Down syndrome 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 Down syndrome, 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 Down syndrome, 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 Down syndrome. 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 Down syndrome, 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 Down syndrome. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON DOWN SYNDROME Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Down syndrome.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and Down syndrome, 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 “Down syndrome” (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: •
Apo E Genotypes and Risk of Dementia in Down Syndrome Source: American Journal of Medical Genetics (Neuropsychiatric Genetics). 88: 344-347. 1999. Summary: This journal article examines the relationship between apolipoprotein E (apoE) genotype and risk of dementia in people with Down syndrome (DS). ApoE genotyping was completed for 45 individuals with DS (20 with and 25 without dementia), and the results were combined with data from other studies in a metaanalysis. The meta-analysis revealed an estimated odds ratio for dementia of 2.74 for apoE4 carriers compared with apoE3/3, similar to that observed in late-onset Alzheimer's disease (AD). Also similar to the pattern seen for late-onset AD, the apoE2 allele was associated with decreased dementia risk in DS (odds ratio for apoE2/2 plus
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apoE2/3 = 0.37). The findings suggest that apoE genotypes are associated with similar risk effects in DS dementia and late-onset AD. 1 table, 22 references. (AA-M). •
Aging and Dementia Among Adults With Mental Retardation and Down Syndrome Source: Topics in Geriatric Rehabilitation. 13(3): 49-64. March 1998. Summary: This journal article reviews the literature on aging and dementia among people with mental retardation (MR) and Down's syndrome (DS). It reviews the epidemiology of Alzheimer's disease (AD) in the general population, AD neuropathology, and estimates of the risk of AD among adults with MR and DS. It explores factors complicating the diagnosis of dementia in people with MR, including the lack of standard assessment protocols for people with MR, limited communication skills in many people with MR, presence of other medical conditions that may mimic dementia, and difficulties in distinguishing AD from pseudodementia and in recognizing subtle signs of early AD. This article focuses on the association between AD and DS, methodological issues in research with the DS population, possible explanations for the discrepancy between the neuropathologic and clinical profiles of AD in the older DS population, and challenges in differentiating between dementia and developmental aging in DS. The article concludes with a discussion of the implications for future research and clinical practice. 109 references.
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Earlier Onset of Alzheimer's Disease in Men With Down Syndrome Source: Neurology. 50: 991-995. April 1998. Summary: This journal article describes a study of sex differences in the age of onset and risk of Alzheimer's disease (AD) in adults with Down syndrome (DS), and the possible influence of apolipoprotein E (apoE) gene status on the association between sex and AD risk. The participants were 111 people with cytogenetically confirmed DS (61 men and 50 women, aged 34 to 71 years), identified through the New York State Developmental Disabilities system. The presence of AD was determined through interviews with caregivers and a review of medical records. ApoE genotyping was performed without knowledge of the participant's medical history or clinical diagnosis. The results revealed that both male gender and the presence of an apoE4 allele were associated with an earlier onset of AD. Men with DS were three times more likely than women to develop AD. Participants with the apoE4/4 or apoE3/4 gene status were four times more likely than those with the apoE3/3 gene status to develop AD. No participant with the apoE2 allele developed AD. There was no evidence of an interaction between sex and apoE gene status in risk of AD. The findings suggest that the higher risk of AD in men may be related to differences in hormone function between men and women with DS that are distinct from those in the general population. 2 figures, 3 tables, 35 references. (AA-M).
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Down Syndrome and Aging: Implications for Rehabilitation Source: Topics in Geriatric Rehabilitation. 13(4): 39-51. June 1998. Summary: This journal article discusses the medical and rehabilitation needs of aging people with Down syndrome (DS). The article focuses on musculoskeletal and other medical problems, but includes information about people with DS who develop Alzheimer's disease (AD). Some research suggests that most or all people with DS will develop AD as they age, but other investigators have challenged this assumption. It is difficult to assess individuals with DS for signs of dementia because diagnostic tools appropriate for determining the presence of AD in DS have not yet been developed. Some studies have found a discrepancy between neuropathological and clinical signs of
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AD in people with DS. Moreover, many studies of people with DS have not collected data on a longitudinal basis, which is important to document functional decline in DS. Investigators suggest that the decline in function used to define dementia in DS may be caused by other conditions which are common in DS, including hypothyroidism, sleep apnea, visual and auditory deficits, atlantoaxial instability, and other orthopedic problems. Furthermore, diagnostic tools and criteria appropriate for determining the presence of AD in DS have not been developed. The authors conclude that rehabilitation professionals can help improve our understanding of the aging process in DS by documenting longitudinal changes in function in this population. 60 references. •
Down Syndrome and Incidence of Alzheimer's Disease. [Letter] Source: American Family Physician. 57(7): 1498. April 1, 1998. Summary: This letter to the editor disputes claims in an earlier article that nearly all people with Down syndrome will eventually develop Alzheimer's disease (AD). The author emphasizes that although AD pathology may develop in virtually all brains of people with Down syndrome over age 35 years, the clinical appearance of AD is considerably less frequent. He argues that many cases of suspected AD may actually be due to such conditions as depression, adjustment disorder, or hypothyroidism. He urges clinicians to take a careful history and explore both common illnesses and those more specific to Down syndrome, to rule out potentially reversible causes of dementia. 4 references.
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Alzheimer-Like Visual Deficits in Down Syndrome Source: Alzheimer Disease and Associated Disorders. 11(2): 88-98. 1997. Summary: This journal article describes a study of visual deficits in Down syndrome (DS). The purpose was to determine whether the pattern of visual impairments seen in Alzheimer's disease (AD) also occurs in Down's syndrome (DS). Participants were 22 adults with DS and 18 adults with mental retardation (MR) of non-DS etiology who were assessed at the Neurology Clinic and Eye Clinic of the Eunice Kennedy Shriver Center for Mental Retardation in Boston, Massachusetts. The DS group consisted of 5 women and 17 men with a mean age of 45.5 years. The MR group was matched to the DS group on the basis of gender ratio and age range. All participants were tested for visual acuity, color discrimination, stereoacuity, and contrast sensitivity function while wearing their own best optical correction. The DS group made more tritanomalous (blue-deficient) errors on the test of color vision than predicted by chance, but not more of other types of hue discrimination errors. The DS group also had higher stereo acuity thresholds than the MR group, and reduced contrast sensitivity across the frequency range. Taken together, the visual deficits observed in the DS group are similar to those seen in AD. Because visual performance was not associated with age, the authors suggest that AD-like visual deficits in DS may present prior to and independent of ageassociated dementia. 2 tables, 59 references.
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Prospective Study of the Prevalence of Alzheimer-Type Dementia in Institutionalized Individuals With Down Syndrome Source: American Journal on Mental Retardation. 101(4): 400-412. 1997. Summary: This journal article describes a prospective study of the prevalence of Alzheimer's disease (AD) in institutionalized people with Down syndrome. Participants were 307 residents of 3 Dutch institutions for people with mental retardation; their mean age was 38.4 years (range 9.8 to 72 years). The residents were followed over a period of 5
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to 10 years. They were assessed each year with the Early Signs of Dementia Checklist, twice a year with the Social Skills Inventory for the Mentally Retarded, and at least once with electroencephalography (EEG). Postmortem neuropathologic examinations were performed when possible. During followup, 56 of the 307 residents (18 percent) developed symptoms of dementia. The mean age of onset of dementia was 56 years. The prevalence increased from 11 percent at ages 40-49 years to 66 percent at ages 50-59, 77 percent at ages 60-69, and 100 percent at age 70 years and older. Of the 13 residents with a clinical diagnosis of dementia who underwent postmortem neuropathological examination, all showed changes consistent with a severe form of AD. The authors conclude that use of a dementia checklist, a cognitive skills inventory, and EEG can reliably detect AD at an early stage. 3 tables, 46 references. •
Young Adults With Down Syndrome as Caregivers for the Elderly With Dementia: An Intergenerational Project Source: Journal of Gerontological Social Work. 26(3-4): 159-170. 1996. Summary: This journal article describes an intergenerational program in which young adults with Down's syndrome were trained to work with older people with Alzheimer's disease and other dementias attending Melabev, an adult day-care program in Jerusalem, Israel. The project evolved from a belief that young adults with Down's syndrome have several characteristics required of dementia caregivers: patience, friendliness, warmth, the ability to tolerate repetition and routine, and a tendency to show affection freely. Students with Down's syndrome received training in independent living, social, and general vocational skills; and then proceeded to a field placement at Melabev and other community sites serving older people with dementia. At Melabev, the students were trained to assist dementia patients in sitting, getting in and out of cars, and putting on and taking off outer clothing; and to help staff by preparing for daily activities, buying and preparing food, washing dishes, and cleaning up at the end of the day. The program was considered beneficial for the students, Melabev staff, and dementia patients, although some problems related to the nature of Down's syndrome were encountered. The article discusses these benefits and problems, and offers suggestions for replication and further study. 22 references.
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Parallels Between Down Syndrome Dementia and Alzheimer's Disease Source: Progress in Clinical and Biological Research. 379:77-102. 1992. Summary: This article identifies common issues, particularly in relation to cognitive changes and risk factors for disease, whose investigation can be used both in the study of Alzheimer's disease (AD) and dementia in Down Syndrome (DS). Discussions include the following: the age-related changes of cognition in normal aging and DS, the relationship between age-related change and dementia, a cognitive profile of dementia in AD and DS, and the risk factors for development of dementia. The article reveals that the risk factors for dementia development in DS are similar to those of AD; that DS patients with dementia appear to show a significant decline in memory ability just like that found in AD patients, that pathological evidence suggests that aging and AD are on a continuum with one another as well as with DS, and that genetic explanations exist in dementia development for both DS and AD. Commonalities between these two diseases suggest that the dementia in DS may be a good model for AD. 7 figures, 54 references.
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Alzheimer's Disease and Down Syndrome: A Review and Implications for Adult Services Source: Education and Training of the Mentally Retarded. 21(2): 144-150. June 1986. Summary: This article discusses how neurological changes associated with Alzheimer's disease consistently have been documented in individuals with Down's Syndrome who are 35 years of age and older. A genetic relationship has been suggested between Down's Syndrome and Alzheimer's disease. In this journal article, the diagnosis of Alzheimer's disease and its progressive behavioral impact on persons with Down's syndrome is discussed.Reports of behavioral changes due to Alzheimer's disease in people with Down's syndrome are inconsistent. Assessment is difficult due to the low levels of mental functioning among people with Down's syndrome. Alzheimer's disease in persons with Down's syndrome may impact on community placement facilities and group homes. Agencies providing such services should anticipate that symptoms of Alzheimer's may increase as their clients with Down's syndrome age. 32 references. (AA-M).
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Expressive Vocabulary in Young Children With Down Syndrome: From Research to Treatment Source: Infant-Toddler Intervention: The Transdisciplinary Journal. 9(1): 87-100. March 1999. Contact: Available from Singular Publishing Group, Inc. Journals Department, 401 West 'A' Street, Suite 325, San Diego, CA 92101-7904. (800) 521-8545. Fax (619) 563-9008. Email:
[email protected]. Website: www.singpub.com. Summary: This article reports on a study of expressive vocabulary development in a population of 130 children with Down syndrome (age range 1 to 5 years). The authors discuss findings in the areas of vocabulary growth, gender differences, signed and spoken vocabulary, referential and grammatical vocabulary, multiword combinations, and morphosyntactic structures. Although there was continuous growth in expressive referential vocabulary from birth through 5 years, age 5 was found to be an important developmental marker for multiword combinations and grammatical vocabulary. By the age of 3 years, children with Down syndrome understand grammatical concepts such as possession and time concepts such as past events, but are not able to use the grammatical markers that represent these concepts until at least age 5. All 5 year olds in the study had begun to use multiword utterances, 77 percent were using plurals, 78 percent were using the possessive marker. Verb tense markers such as ing and ed were beginning to emerge, but were used by fewer than half of the children. The authors stress that early treatment using Total Communication is needed to facilitate expressive vocabulary development during the first 3 years. The authors discuss treatment applications for early intervention, and then intervention for the birth to age 5 period. 8 tables. 25 references.
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Gestures and Words in Early Development of Children with Down Syndrome Source: JSLHR. Journal of Speech, Language, and Hearing Research. 41(5): 1125-1135. October 1998. Contact: Available from American Speech-Language-Hearing Association (ASHA). Product Sales, 10801 Rockville Pike, Rockville, MD 20852. (888) 498-6699. TTY (301) 8970157. Website: www.asha.org.
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Summary: This article reports on a study that investigated the development of language and communication in children with Down syndrome (DS). More specifically, the aim was to examine the relations among verbal comprehension, verbal production, and gesture production in the very early stages of development. Forty children (age range 10 to 49 months) with DS and 40 children with normal development (age range 8 to 17 months) participated in this study. The communicative and linguistic development of children with DS was measured by administering the Italian version of the MacArthur Communicative Development Inventory (the children with DS were from two Italian health centers). The children with DS were severely delayed in reaching the developmental stages when compared with normally developing children. In such children, a dissociation emerged between verbal comprehension and production, in favor of comprehension, whereas a synchronous development was found between vocal lexical comprehension and gestural production. The individual differences previously reported in these children are also evident in all domains examined. There were no significant differences between children with DS and typically developing controls matched for lexical comprehension on verbal production. However, the two groups differed significantly in gestural development, suggesting a gesture advantage in children with DS compared with controls matched for word comprehension. The authors discuss some possible reasons for this dissociative profile. (AA). 3 figures. 4 tables. 54 References. •
Down Syndrome: A Multidisciplinary Perspective Source: Journal of the American Academy of Audiology. 6(1): 39-46. January 1995. Summary: Trisomy 21 (Down syndrome), a genetic disorder resulting from a chromosomal abnormality, is one of the most common forms of mental disability in the U.S. This article stresses the importance of a multidisciplinary team in the provision of services to individuals with Down syndrome so that prevention of further disabilities, improved outcomes of medical interventions, and appropriate habilitative and educational planning may follow. The authors focus on the role of the audiologist in this multidisciplinary approach. They stress that audiologic and communication interventions should be established at the earliest possible time to maximize an individual's development potential. Specific topics covered include genetic considerations, outer and middle ear anomalies, inner ear and retrocochlear anomalies, hearing loss, audiologic considerations, and language and speech planning. 2 tables. 31 references. (AA-M).
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On the Nature of Language Impairment in Down Syndrome Source: Topics in Language Disorders. 13(3): 20-35. May 1993. Summary: This article reports on a study of the responses of a group of adults with Down syndrome to a language elicitation test. The responses are compared with the responses from a group of adults with retardation of unknown origin. In light of evidence for different patterns of language acquisition in the two groups, they discuss the possible nature and source of the biological constraints on language learning in Down syndrome and consider the implications of biologically imposed limits on language acquisition for clinical intervention. They focus on those responses that provide evidence of mastery of the auxiliary verb system. The article is from a special issue on maximizing communication competence in adults with mental retardation. 3 tables. 41 references. (AA-M).
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Down Syndrome: An Otolaryngologic Perspective Source: Journal of Otolaryngology. 21(6): 394-397. December 1992. Summary: This article examines the association between Down syndrome and various pathological entities related to the head and neck. The authors stress that the otolaryngological manifestations of Down syndrome often masquerade as common and seemingly trivial conditions. Behind this facade lies a broad spectrum of disease that can impair functioning and jeopardize survival. Topics include ear pathology, including the incidence of otitis media, middle ear effusion, hearing loss, and anatomic abnormalities of the auditory canal and eustachian tube; and the diagnosis, pathology, treatment, and complications of sleep apnea. The authors note that altered anatomy coupled with diminished intelligence and an increased propensity for infection in this population complicate diagnosis. They reiterate the need for early diagnosis and treatment so that the potential of this patient group is fulfilled. 1 table. 18 references. (AA-M).
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Prevalence of IgA-Antigliadin Antibodies and IgA-Antiendomysium Antibodies Related to Celiac Disease in Children with Down Syndrome Source: Pediatrics. 101(2): 272-275. February 1998. Contact: Available from American Academy of Pediatrics. P.O. Box 927, Elk Grove Village, IL 60009-0927. Summary: This article reports on a study undertaken to investigate the prevalence of celiac disease in children and adolescents with Down syndrome. Forty-three children and adolescents with Down syndrome were screened for IgA-antigliadin antibodies (AGA) and IgA-antiendomysium antibodies (EMA). Patients found to be positive for either type of antibodies were investigated further with intestinal biopsy. None of the 43 patients had known celiac disease at entry into the study; 37 percent (16 patients) were found to have AGA levels above normal, and 16 percent (7 patients) were found EMA positive. Of the 15 patients who underwent biopsy, 8 manifested villous atrophy (the hallmark of celiac disease). Villous atrophy was present in all 7 of the EMA positive patients, whereas the villi were normal in 7 of the 13 AGA positive patients who underwent biopsy. The authors conclude that EMA is a good immunologic marker for use in screening for celiac disease, and screening is justified in patients with Down syndrome. 2 figures. 27 references. (AA-M).
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Stimulated Parotid Salivary Flow Rate in Patients with Down Syndrome Source: SCD. Special Care in Dentistry. 22(1): 41-44. January-February 2002. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Summary: Saliva is essential for oral defense against infections. Decreased salivary secretion may result in increased dental caries (cavities), oral mucosal changes, an altered sense of taste, difficulty in swallowing, and oral pain. This article reports on a study that documented the parotid gland saliva secretion at different ages in a group of subjects with Down syndrome. Saliva was collected from 39 patients aged 11 to 62 years old, by means of a parotid salivary gland cup and under standardized conditions of stimulated secretion. The rate of salivary secretion in the entire group of patients with Down syndrome was lower than that of healthy controls and lower in the older study group compared with the younger group. Institutionalized subjects or those living in hostel-like apartments had a lower secretion rate than those living at home. In analyses of the four factors (Down syndrome, hypothyroidism, institutionalization, and age),
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Down syndrome was found to be the only variable significantly related to flow. These findings indicate that stimulated parotid salivary hypofunction in Down syndrome subjects is mainly related to their genetic disorder. 2 tables. 30 references. •
Severe Impairment of Secretory Ig Production in Parotid Saliva of Down Syndrome Individuals Source: Journal of Dental Research. 81(5): 308-312. May 2002. Contact: Available from International Association for Dental Research. Subscription Department, 1619 Duke Street, Alexandria, VA 22314. (703) 548-0066. Fax (703) 548-1883. Summary: Infections associated with Down Syndrome (DS) are prevalent in the mucosal-gastrointestinal and respiratory systems, for reasons that are uncertain. This article reports on a study undertaken to assess the levels of parotid salivary immunoglobulins (Ig) in a group of DS individuals as a possible factor in the susceptibility of mucosal surfaces to infections. The study included 29 DS and 10 agematched and sex-matched healthy individuals. The secretion rates of IgA and IgG were diminished by 83 percent and 75 percent, respectively, in the DS population, whereas the secretion rate of IgM was not statistically significantly lower. Analysis of the data suggests that DS individuals are immunodeficient in the humoral mucosal immune response. This may explain, in part, the high incidence of recurrent infections in target organs of the secretory immune system in DS subjects. 3 figures. 1 table. 34 references.
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Prevalence of Numeric Anomalies in the Permanent Dentition of Patients with Down Syndrome Source: SCD. Special Care in Dentistry. 21(2): 75-78. March-April 2001. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Summary: This article reports on a study undertaken to evaluate the prevalence of numeric anomalies in the permanent dentition (teeth) of patients with Down syndrome by means of panoramic radiographs. The sample consisted of panoramic radiographs (x rays) from 70 subjects. The authors examined the radiographs to detect hypodontia (less than the normal number of teeth, which is 32) as well as supernumerary teeth (any tooth in addition to the normal number). Results confirm the high prevalence of hypodontia among patients with Down syndrome (60 percent) mostly with mild expression. The teeth most often missing were the upper lateral incisors, usually bilaterally (both sides), followed by the lower second premolars and upper second premolars. Supernumerary teeth were seen in 6 percent of the subjects, and the concomitant occurrence of hypodontia and supernumerary teeth occurred in one patient. The authors note that the clinical relevance of the early recognition of hypodontia and supernumerary teeth in any patient requires adequate treatment planning, for example, the maintenance of deciduous (temporary or primary) teeth or an early orthodontic intervention. 2 figures. 4 tables. 18 references.
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Treating the Patient with Down Syndrome Source: Journal of Contemporary Dental Practice. 2(4). November 15, 2001. Contact: Available from Journal of Contemporary Dental Practice, an online journal. Website: www.thejcdp.com.
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Summary: There are large numbers of individuals with Down syndrome living and working in the general community, thus it is likely that general dental practitioners will encounter patients from this group. This continuing education course is designed for general dentists and hygienists. The course materials cover the physical characteristics of patients with Down syndrome and the relationship of these characteristics to general dental care. The author discusses the prevalence of dental disease in this population, as well as techniques for effective patient management. Home care issues are also addressed. The purpose of the course is to enable dentists and hygienists to feel comfortable in treating most patients with Down syndrome within the general dental practice. The materials include a list of objectives and a posttest with which readers can obtain continuing education credit. The program is designed to be completed online. 9 figures. •
Periodontopathic Bacteria in Children with Down Syndrome Source: Journal of Periodontology. 71(2): 249-255. February 2000. Contact: Available from American Academy of Periodontology. Suite 800, 737 North Michigan Avenue, Chicago, IL 60611-2690. (312) 573-3220. Fax (312) 573-3225. Summary: Individuals with Down syndrome (DS) often develop severe early onset periodontal diseases. This article reports on a study that examined the prevalence of periodontopathic bacteria in DS children to determine if specific pathogens are acquired in their childhood. The subjects were 60 DS children (2 to 13 years old, five in each age bracket) and 60 age matched controls. Ten pathogens were surveyed in subgingival plaque samples using a polymerase chain reaction. Periodontal status was evaluated by probing depth, bleeding on probing, and gingival index. No significant difference in periodontal status was observed between the DS and control groups, however, all of the pathogens were detected with greater frequency in the DS children. A cluster analysis of the microbial profiles of the DS subjects showed that gingivitis severity was associated with increased varieties of the harboring pathogens and the distribution of Porphyromonas gingivalis. The authors conclude that these results suggest that various periodontopathogens can colonize in the very early childhood of DS patients and the maturation of subgingival components, including P. gingivalis, plays an important role in the initiation of gingival inflammation. 2 figures. 2 tables. 29 references.
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Prevalence of Tooth Transposition, Third Molar Agenesis, and Maxillary Canine Impaction in Individuals with Down Syndrome Source: Angle Orthodontist. 70(4): 290-296. August 2000. Contact: Available from Allen Marketing and Management. P.O. Box 1897, Lawrence, KS 66044-8897. (785) 843-1235. Fax (785) 843-1274. Summary: Alterations in the size, morphology (shape) and number of teeth are among the many inherited disorders that have been reported in individuals with Down syndrome. By contrast, third molar agenesis (lack of development) and tooth transposition have been largely ignored and the prevalence of canine impaction has not been reported. This article reports on a study undertaken to quantify the occurrence of these anomalies in a group of individuals with Down syndrome, using standardized records, which included a clinical examination, dental cases, and a panoramic radiograph (x ray). The results saw a notably high prevalence of third molar agenesis (74 percent of individuals older than 14 years), canine impaction (15 percent), and maxillary canine and first premolar transposition (15 percent), compared to published figures from random population samples. The authors stress that these anomalies should not be
12 Down Syndrome
seen as separate, independent entities, but as associated phenomena. The slow rate of cell growth and a consequent reduced cell number that characterize this syndrome may be responsible for the underdevelopment of the upper jaw, the delayed dental development, the reduction in teeth number and size, and the altered path of canine eruption. 3 figures. 1 table. 43 references. •
Significance of Oral Health in Persons With Down Syndrome: A Literature Review Source: Developmental Medicine and Child Neurology. 41(4): 275-283. April 1999. Summary: Down syndrome (DS) is an autosomal chromosomal anomaly that affects approximately 1 in 700 to 800 live births. Many of the medical and physiological characteristics of DS have direct consequences for the oral health of subjects affected with DS. There are also indirect consequences for the quality of life of persons with DS and their caregivers. This article provides an overview of the literature concerning the orofacial problems confronting patients with DS and reviews the different treatment options available. Topics include anatomical consideration, mastication (chewing) and swallowing, dental disease, bruxism, and dental trauma (patients with DS may be more prone to falls). Systemic dysfunction (such as immunological deficiency) in this population may predispose to oral disease, which may in turn aggravate systemic disease. The authors emphasize that regular reviews, preferably by a specialist team, should be undertaken to identify and prevent both functional problems and disease processes. These patients should be seen at least every 6 months, but more regularly should specific problems arise. These regular reviews should have the following aims: early introduction to the dental environment in order to facilitate subsequent preventive intervention, diagnosis and, if possible, to allow appliance therapy; early neuromuscular stimulation of oral proprioception essential for full development of orofacial function in the infant; education of caregivers with regard to nutrition, taking into account chewing function, food texture, caries prevention, and fluoride administration; and institution of a personalized oral hygiene regimen for the prevention of periodontal disease, taking into account the motor capacity of the patients and aiming for autonomy of care. 3 figures. 108 references.
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Neutrophil Chemotaxis in Down Syndrome and Normal Children to Actinobacillus Actinomycetemcomitans Source: Journal of Clinical Pediatric Dentistry. 22(2): 141-146. Winter 1998. Contact: Available from Journal of Clinical Pediatric Dentistry. P.O. Box 830259, Birmingham, AL 35283-0259. Summary: During the last decade a lot of attention has been diverted to the study of Actinobacillus actinomycetemcomitans (Aa) as the principal microorganism in the pathogenesis of periodontal disease. Because of the defective body defenses, there is an increased likelihood of periodontal disease among patients with Down syndrome. The authors of this article attempt to correlate the relationship between the gingival and periodontal health status to the isolation of Aa from the subgingival plaque in children with Down syndrome. They compare this to the neutrophil chemotactic activity in normal subjects. The authors observed a strong observation between the occurrence of Aa as well as significant differences between the normal and Down syndrome subjects in neutrophil defense activity. Thus the higher prevalence of periodontitis diagnosed in children with Down syndrome seems to be more related to the impaired host defense mechanism rather than to the occurrence of specific periodontal pathogens. 3 figures. 2 tables. 52 references. (AA-M).
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Dental Care for the Patient with Down Syndrome Source: Down Syndrome Research and Practice. 5(3): 111-116. 1998. Contact: Down Syndrome Educational Trust. Subscriptions, DownsEd, The Sarah Duffen Centre, Belmont Street, Southsea, Hampshire, P05 1NA, England. +44 (0) 1705 824261. Fax: +44 (0) 1705 824265. E-mail:
[email protected]. Website: www.downsnet.org/dsrp. Also available from Down Syndrome: Health Issues. Website: www.ds-health.com/dental.htm. Summary: This article reports on a clinical and literature review of the special dental considerations unique to individuals with Down syndrome. The author is both a dentist and parent of a child with Down syndrome. The author discusses the physical and orofacial characteristics of Down syndrome, including the teeth, gingiva, tongue, palate, and occlusion. Incidences of dental decay and periodontal disease are discussed as are recommendations for treating these diseases in persons with Down syndrome. The author notes that most, if not all, persons with Down syndrome have some type of occlusal disharmony; orthodontic therapy is discussed. The author also discusses medical problems associated with Down syndrome, the social and emotional factors involved in dental treatment, techniques to help children with Down syndrome become cooperative dental patients, how to choose the right dentist for a child with Down syndrome, how parents can communicate effectively with the dental staff, proper home care, and the prevention of dental disease (including the most recent dental products). The author concludes that dental care for the patient with Down syndrome can be achieved in the general practitioner's office in most instances with minor adaptations. Although this population has some unique dental care needs, few patients require special facilities in order to receive dental treatment. 24 references.
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Concomitant Occurrence of Hypodontia and Supernumerary Teeth in a Patient with Down Syndrome Source: SCD. Special Care in Dentistry. 17(2): 54-57. March-April 1997. Summary: This article reports the case of a patient with Down syndrome in whom concomitant hypodontia and supernumeraries are present. Concomitant hypodontia and supernumerary teeth are relatively rare, and this is the first case reported in a patient with Down syndrome. The article first describes Down syndrome, including its epidemiology, general and facial features, and dental and oral anomalies. The case report of a 12 1/2 year old Caucasian girl with Down syndrome and mild mental retardation is then presented. Her main dental complaint was that a new tooth had recently 'appeared in the roof of her mouth.' An evaluation of the radiographs showed missing maxillary right and left second premolars and also a mandibular right second premolar. The maxillary left and mandibular left, and right second molars were developing normally, but the maxillary right second molar appeared peg-shaped. The authors note that a conservative approach to management will be pursued, with the accent on oral hygiene reinforcement and prevention. 3 figures. 32 references. (AA-M).
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Down Syndrome: A Review of the Literature Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 84(3): 279-285. September 1997. Summary: This article reviews the literature on Down syndrome, focusing on various systemic and oral anomalies, clinical manifestations, and recommendations for the dental management of persons with Down syndrome. From the time Down syndrome
14 Down Syndrome
was diagnosed by phenotype, to the present when karyotyping distinguishes chromosomal subgroups, increasingly sophisticated tests and treatments have influenced the lives of Down syndrome patients. Medical advances, special educational programs, and increasing social acceptance of disabled people in the community have resulted in current trends of normalization and deinstitutionalization of these patients. The author emphasizes that once a dentist is familiar with a patient's medical history and takes needed precautions, patients with Down syndrome can be treated routinely in a dental office. 39 references. (AA-M). •
Oligodontia: A Radiographic Comparison of Subjects with Down Syndrome and Normal Subjects Source: SCD. Special Care in Dentistry. 17(5): 137-141. September-October 1997. Summary: This article reports on a study in which panoramic radiographs and clinical records were used to investigate developmentally absent permanent teeth in 98 subjects with Down syndrome (trisomy-21). This retrospective study was based on the records and panoramic radiographs of subjects from approximately five years of age (the age at which mineralization of the permanent tooth germ could be identified) to their current age. The time period covered by records ranged from 6 to 28 years. The majority of subjects with Down syndrome (63 percent) exhibited oligodontia (missing teeth), and many subjects were missing two or more teeth (53 percent). The most frequently absent teeth were the lower lateral incisors (23.3 percent), the upper second premolars (18.2 percent), the upper lateral incisors (16.5 percent), and the lower second premolars (15.3 percent). In general, the distribution of the developmentally absent teeth was similar for teeth in homologous positions on either side of the midline or between the maxilla and the mandible. The only significant exceptions to this pattern were seen with the central incisors and the second molar. This study's findings suggest a high risk of oligodontia in subjects with Down syndrome. 3 figures. 2 tables. 13 references. (AA-M).
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Toxic Shock and Down Syndromes in a Dental Patient: A Case Report and Review of the Literature Source: Special Care in Dentistry. 14(6): 246-251. November-December 1994. Summary: In this article, the authors first present a literature review of toxic shock syndrome (TSS), including epidemiology, etiology, signs, symptoms and management, and its relationship to infection susceptibility in the Down syndrome patient. The authors then present a case of a Down syndrome patient with TSS, focusing on the role of odontogenic infection. They report the patient's medical history, social history, and dental history. They conclude with a discussion of the management of the dental patient with a TSS history. 3 figures. 2 tables. 42 references. (AA-M).
Federally Funded Research on Down Syndrome The U.S. Government supports a variety of research studies relating to Down syndrome. 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 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).
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database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Down syndrome. 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 Down syndrome. The following is typical of the type of information found when searching the CRISP database for Down syndrome: •
Project Title: 10TH INTERNATIONAL MEETING CHROMOSOME 21 & DOWN SYNDROME Principal Investigator & Institution: Yarowsky, Paul J. Scientist; Pharmacol & Exper Therapeutics; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2002; Project Start 26-SEP-2002; Project End 29-SEP-2002 Summary: (provided by applicant): The objective of the 10th International Meeting of Chromosome 21 & Down Syndrome is to bring together investigators from the international community with a broad spectrum of research interests to discuss the current state of knowledge regarding Down syndrome and human chromosome 21. Topics for discussion are designed to encompass all relevant areas of biology, molecular biology, and medicine, including functional genomics and neurobiology. Invited speakers will present an overview highlighting topical issues. These introductions will be followed by platform presentations from submitted abstracts. The organizers anticipate a small but highly interactive meeting to facilitate the exchange of the latest ideas between senior and junior scientists, including postdoctoral fellows. Following the sequencing of chromosome 21, researchers are putting the results of these molecular analyses into biological context. This can best be done with a multidisciplinary group of researchers including those specializing in the mental retardation and cognitive deficits of Down syndrome, the neurobiology of Down syndrome, congenital heart defects, immune deficits, leukemia, craniofacial abnormalities, communicative and digestive disorders, and premature aging, as well as genomic research, transgenic mouse construction and analysis, and mouse behavioral studies. It is anticipated that this conference will foster interaction across disciplines, help to focus and redirect research efforts for maximal use of developing data, and establish new collaborations and avenues of investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A CLINICAL TRIAL OF DONEPEZIL FOR DOWN SYNDROME Principal Investigator & Institution: Kishnani, Priya S. Assistant Professor; Pediatrics; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: (Adapted from the applicant's abstract): The primary hypotheses of the proposed project is that administration of Donepezil to young adults with Down syndrome (DS) will improve adaptive functioning and expressive language as measured by a change from baseline to endpoint at 24 weeks of therapy. DS is the most common genetic cause of mental retardation worldwide. Cognitive and functional deficits, of variable degree, are seen in all subjects with DS and currently there is no
16 Down Syndrome
approved treatment for these domains. An impaired cholinergic system, which persists throughout the lifespan, has been detected early in life in individuals with DS. This cholinergic deficit is believed to underlie many of the cognitive and functional impairments in DS. A therapy that increases the bioavailability of acetylcholine could produce improvements in cognition and consequently, adaptation in DS. Alzheimer's disease (AD) is a model for this effect. Donepezil Hydrochloride, an FDA-approved second generation cholinesterase inhibitor, is currently the most widely-used medication for the pharmacotherapy of cognitive and functional deficits in AD. A previous open label study of DS adults found Donepezil to be well tolerated with improvement in expressive language and adaptive domains. Rationale for its use in young DS individuals is to enhance availability of acetylcholine because of its key role in learning and not to treat symptoms of AD in DS. The proposed study is a single Center, randomized 24-week double-blind, placebo-controlled study with a subsequent 24-week open treatment and six-week washout phases. Sixty individuals with DS will participate, and half will receive drug during the first 24 weeks. The primary endpoints are the adaptive behavior composite score of the Vineland Adaptive Behavior Scales (VABS) and expressive language subtests of the Clinical Evaluation of Language Fundamentals (CELF-3) comparing the treated group to the control group after the 24 weeks of blinded treatment. A number of secondary aims will investigate effects of treatment of specific components of cognition, i.e., memory and mood. Safety and tolerability will also be evaluated. As DS individuals are now living longer, improving their quality of life and maximizing their developmental potential are of paramount importance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: A GENETIC ANALYSIS OF MINIBRAIN KINASE IN C. ELEGANS Principal Investigator & Institution: Raich, William B. Ctr for Neurobiology Behavior; Columbia University Health Sciences New York, NY 10032 Timing: Fiscal Year 2001; Project Start 01-SEP-2001 Summary: The goal of this research proposal is to identify molecular pathways involving minibrain kinase (mnbK), both in normal neuronal function and in the cognitive defects of Down syndrome. Studies of partial trisomy of chromosome 21 suggest that a considerable portion of the Down syndrome phenotype result from a 2Mb region at the 21g22.2 region; mnbK localizes to this genomic region. Overexpression of mnbK in mice causes severe defects in learning and memory, strongly implicating mnbK in the cognitive defects of Down syndrome. Currently, the substrates and regulators of mnbK are unknown. To elucidate this pathway, the Caenorhabditis elegans mnbK homologues mbk-1 and mbk-2, will be investigated. I propose to characterize the expression and subcellular localization of the mbk gene products, generate null alleles via chemical mutagenesis coupled with population PCR, and simulate the Down condition by overexpressing the wildtype and activated gene products. As a tool for determing the focus of MBK activity, the tetracycline-dependent transactivator system will be adapted to C. elegans, a system that permits temporally and spatially regulated gene expression. Candidate genes will be tested to determine if they belong to a mbk pathway, and pilot suppressor and/or enhancer screens will be performed to identify upstream and downstream components in an unbiased manner. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: A STIMULUS CONTROL ANALYSIS OF ATTENDING Principal Investigator & Institution: Serna, Richard W. Associate Professor; Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: In typically-developing children, initially slow, one-at-a-time word learning is followed by an apparent "explosion" in their lexicon. One estimate suggests that children are learning up to nine new words a day through slow and deliberate effort (e.g., McLean, 1993). Yet word learning is a foundational component of human development, necessary for advanced linguistic functions (e.g. syntactic operations) and contributing to complex representation skills (for instance, categorization; Bowerman, 1988). Yet word learning is a foundational component of human development, necessary for advanced linguistic; Bowerman, 1998). To the extent that a cognitive disability interferes with cord learning, progress in these domains will be correspondingly limited. It is therefore essential to explore in detail the nature of lexical impairments in mental retardation. The existence of difficulties in lexical acquisition among individuals with severe mental retardation raises important questions. When rapid vocabulary expansion occurs, what linguistic/cognitive processes support that learning? When it does not occur, what skills are deficient or absent? A phenomenon called fast mapping may be of greatest potential relevance for rapid vocabulary expansion. Fast mapping refers to a "quick, initial, partial understanding of a 'new' word's meaning" derived from the context of word use )Rice, 1989, p.152). Fast mapping has been argued to facilitate the vocabulary expansion. This proposed role has received empirical confirmation in typical youngsters and children with Down Syndrome )Mervis & Bertrand, 1994, 1995). Yet evidence from children with atypical cognition/language has recently challenged the universality of this relation. My own studies (Wilkinson & Green, 1997) have added to preliminary evidence of selective deficits in fast mapping among individuals with severe mental retardation, Williams Syndrome, or specific language purpose of vocabulary expansion. These recent findings oblige a more systematic analysis of the precise role of the principle in learning outcomes in mental retardation. Is fast mapping at risk in individuals with severe mental retardation, potentially limiting their vocabulary expansion? I propose a five-year study of vocabulary expansion and delay, focusing specifically on rapid expansion of an extant, but limited, vocabulary. This study will implement methods developed by the applicant (Wilkinson & Green, 199) that for the first time enable systematic analysis of unresolved questions of lexical expansion in severe mental retardation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADAPT NEURODEGENERATION
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OXIDANT
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Principal Investigator & Institution: Davies, Kelvin J. Gerontology; University of Southern California 2250 Alcazar Street, Csc-219 Los Angeles, CA 90033 Timing: Fiscal Year 2001; Project Start 01-FEB-2000; Project End 31-JAN-2005 Summary: We are interested in a possible link between oxidative stress, aging and neurodegenerative diseases. In recent studies of adaptation to oxidative stress we have identified several previously unknown genes (in addition to confirming the overexpression of several known genes) that appear to provide stress protection in isolated hamster cells in culture. These "adapt" genes include: adapt15, adapt33, adapt66, adapt73, adapt78, and adapt 116. Although our studies indicate that full
18 Down Syndrome
adaptation depends upon both transcription and translation, it is not clear which genes are actually required. Although each of these newly discovered genes is worthy of detailed study, adapt78 whose mRNA levels increase more than 50 fold in adaptation, in particular stands out. In screening studies employing autopsy samples from human brains, we have now found that the human homologue of adapt78 exhibits extremely high levels of expression in brain autopsy samples from Alzheimer's disease patients, and low levels of expression in brain samples encompassing the substantia nigra from patients who died with Parkinson's disease. Recently, it has become clear that our adapt78 is identical to (or at least highly homologous with) the simultaneously independently discovered Down syndrome critical region 1 (DSCR1) gene of chromosome 21. Furthermore, two different isoforms of both adapt78 and DSCR1 are differentially expressed; corresponding to differentially spliced forms of exons 1-5, 6, 7 and exons 4-5, 6, 7. We propose to now carefully study expression of both isoforms of the human adapt78 gene in different brain regions, using the more sensitive techniques of RT-PCR and in situ hybridization. We plan to study adapt78 expression as a function of age, in brain autopsy samples from otherwise healthy individuals, since adapt78 expression may well vary with age. We will perform detailed studies of brain samples from Alzheimer's disease patients, Parkinson's disease patients, and Down syndrome patients in order to carefully determine both qualitative and quantitative differences in expression of both isoforms of adapt78 mRNA. Localization of adapt78 mRNA expression by cell type will also be studied. We also will synthesize and characterize the (1-5, 6, 7 and 4-5, 6, 7) Adapt78 proteins and generate antibodies to them in order to study expression of the actual proteins in all cell and brain samples. In cell culture studies, with PC-12 cells, we will test the hypothesis that inducible overexpression of adapt78 may confer an oxidative stress resistance phenotype. We will also test the ability of inducible adapt78 overexpressing cells to overcome the lethal oxidizing effects of glutathione deficiency, caused by expression of antisense message to gamma glutamylcysteine synthetase. These studies will allow us to begin to investigate our hypothesis that aging, and perhaps certain neurodegenerative diseases, involving defects in the expression of adapt78 and other adaptive genes required to cope with the deleterious effects of oxidative stress. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADULT MOUSE MODEL FOR DOWN SYNDROME Principal Investigator & Institution: Davisson, Muriel; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: The long term goal of this Project is to define the genetic and biological bases for abnormalities seen in individuals with Down syndrome (DS; Trisomy 21, Ts21), using genetically defined and genetically manipulated mouse model systems. The Down syndrome region of human Chromosome (Chr) 21 is conserved in at least three mouse chromosomes Chr 10, 16, and 17- with the largest segment in Chr 16. My research group has produced a mouse strain that carries segmental trisomy [Ts(1716)65Dn] for most of the region of mouse Chr 16 that is homologous with the Down syndrome region of human Chr 21 genes at dosage imbalance in this model by combining Ts65Dn with transgenes containing genes from the region of human Chr 21 that is conserved in mouse Chr 10; (2) study the effects of individual candidate genes in the Ts65DN segment by combining in mouse Chr 10; (2) study the effects of individual candidate genes in the Ts65Dn segment by combining it with targeted mutations for the singleminded (Sim2) and minibrain (Dyrk) homologs of Drosophila genes, which are
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important in central nervous system development and glycolysis; (3) analyze the behavior and pathology of the combining mice produced and (4) carry out neurological and electrophysiologic studies on the combination mice produced. The evaluation of neural function will include in vitro recording from fresh brain slices to assess synaptic transmission and plasticity. In vivo procedures, such as electrocorticograms and quantification of tremor activity also will be used. These assessments will be complemented by the analysis of hippocampal place cell activity and dendritic morphology of a limited number of strains. This research will provide not only a better understanding of the role of single genes in the Down syndrome phenotype but also a more complete adult mouse model for testing therapeutic intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AGE-RELATED CHANGES IN TS65DN MOUSE FOREBRAIN & LEARNING Principal Investigator & Institution: Hyde, Lynn A. Pediatrics; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-NOV-2000 Summary: Ts65Dn mice are a model of Down syndrome and may be useful as a model Alzheimer's disease as well. Alzheimer's patients lose basal forebrain cholinergic (BFC) neurons and cholinergic function. Similarly, Ts65Dn mice lose BFC neuronal markers earlier than control littermates, but the functional effects of this loss has not been examined. This proposal will examine the functional effects of premature loss of BFC neurons in Ts65Dn mice on learning tasks that depend on the BFC system and two areas it innervates, the hippocampus and prefrontal cortex. To this end, learning will be assessed in tasks that have been shown to be dependent on BFC function (delayed nonmatch and match to sample, radial arm maze spatial working memory, and passive avoidance), the hippocampus (spatial, but not non-spatial, radial arm maze) and/or prefrontal cortex (behavioral flexibility). Further, we will relate learning in these tasks to BFC neuronal number and function at 3 ages that span the progression of BFC loss in Ts65Dn mice. Importantly, this proposal will determine if the cholinergic cell loss parallels the learning deficits. Data from this study may aid in understanding of the role that the loss of cholinergic neurons and function may play in dementia seen in Alzheimer's disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALTERNATIVE SPLICING OF THE DROSOPHILA DSCAM PREMRNA Principal Investigator & Institution: Graveley, Brenton; Genetics & Developmntl Biology; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): The long-term goals of this proposal are to understand how the alternative splicing of the Drosophila Down syndrome cell adhesion molecule (Dscam) gene is regulated and to determine the mechanism by which Dscam alternative splicing is mutually exclusive. The Dscam gene encodes an axon guidance receptor that plays an important role in neural development and is the most extensively alternatively spliced gene known to date. The Dscam gene contains 115 exons, 95 of which are alternatively spliced. The alternative exons are organized into 4 distinct clusters containing 12, 48, 33 and 2 mutually exclusive exons each. Because the
20 Down Syndrome
exons within each cluster are alternatively spliced in a mutually exclusive manner, it is possible that 38,016 different Dscam isoforms can be expressed. It has been proposed that each Dscam isoform might interact with a different set of axon guidance cues and that the collection of Dscam isoforms expressed by a cell will be directly involved in guiding neurons to different addresses. It is therefore likely that individual neurons must in some way be programmed to splice the Dscam pre-mRNA in specific ways. Thus understanding the mechanisms regulating Dscam alternative splicing will provide insight into the genetic program that specifies neural wiring. This proposal is aimed at understanding the mechanisms involved in regulating the alternative splicing of the Dscam exon 4 cluster which contains 12 mutually exclusive exons. First, we will identify RNA sequences involved in the regulation of Dscam alternative splicing and the proteins that bind to these elements. Second, we will determine the mechanism involved in the developmental regulation of exon 4.2 alternative splicing. Third, we will determine the mechanism by which the SR protein B52 and the general splicing factor dU2AF modulate exon 4.4 alternative splicing. Finally, we will determine the mechanistic basis by which alternative splicing of the Dscam exon 4 cluster is mutually exclusive. Together, these experiments will provide significant insight into the mechanisms involved in regulating alternative splicing, the mechanism responsible for mutually exclusive alternative splicing, and the genetic program that determines the specificity of neural wiring in Drosophila. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ALZHEIMER'S DISEASE IN DOWN SYNDROME: ANTIOXIDANT TRIAL Principal Investigator & Institution: Lott, Ira T. Pediatrics; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The objective of this pilot clinical trial is to obtain information on the tolerability, safety, and efficacy of a high potency combinatorial supplement in the treatment of Alzheimer disease (AD) in Down syndrome (DS). Individuals with DS have an increased incidence of AD and evidence of oxidative stress in brain. The DS population is an excellent candidate for antioxidant intervention. The trial will conform to a double-blind, placebo-controlled, and repeated analysis of variance design. The supplement will consist two cellular antioxidants (vitamins E 900 IU/day and C 200 mg/day) and a mitochondrial antioxidant (alpha-lipoic acid 600 mg/day). The clinical diagnosis of AD in DS will be made by the investigators utilizing their previous experience with DSM-IV criteria for dementia in DS. There are three specific aims: 1) to determine whether cognitive measures are improved by antioxidant supplementation. Outcome measures have been shown to have reliability and validity for DS. They comprise three informant scales (Dementia Rating Scale for Persons with Mental Retardation, Neuropsychology Behavior and Affect Profile, Vineland Adaptive Scales) and three direct assessments (Severe Impairment Battery, Brief Praxis Test, and the FULD-Object/Memory Test-modified); 2) to determine whether plasma biomarkers of lipid oxidative damage (malondialdehyde, isoprostanes), protein oxidative damage (carbonyl group formation), levels of beta-amyloid, and vitamin E levels will be altered in subjects receiving the diet; and 3) to determine the safety and tolerability of the antioxidant supplementation utilizing checklists for adverse events, clinical chemistries, and measures of medication compliance. All study measures will be obtained at baseline and at 6-month intervals for a total of 24 months of treatment. All study patients will be on an acetylcholinesterase inhibitor. Power analysis configured on the primary outcome
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measures supports a study group of 30 treated and 30 placebo randomized patients. Database management will facilitate analysis of the 24-month observations. The data from this study is intended to provide information relevant to the indications for a multicenter definitive clinical trial of antioxidants in DS. Since the process resulting in AD in DS is age dependent across the lifespan, a positive result from this pilot trial may have implications for utilizing high potency combinatorial antioxidants at earlier age epochs in DS. The pilot trial should also contribute information as to the possible role of antioxidants in the treatment or prevention of AD in the general population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANALYSIS AND CONTROL OF CHROMOSOME MOVEMENT Principal Investigator & Institution: Nicklas, R B. Zoology; Duke University Durham, NC 27706 Timing: Fiscal Year 2001; Project Start 01-JAN-1976; Project End 30-NOV-2005 Summary: (Verbatim from the applicant's abstract): The goal is to understand precise chromosome movement and the accurate distribution of chromosomes to the daughter cells in mitosis and meiosis. Errors in distribution can lead to cancer and to Down syndrome and other chromosome disorders in humans. How cells avoid errors is the subject of this project. Mechanical tension from mitotic forces is the key. Early in mitosis, chromosomes move to a position quite precisely midway between the spindle poles. The movement is powered by motile kinetochores (the structures that attach the chromosome to spindle microtubules). Kinetochores switch between pulling and an inactive, 'neutral' state. The switch may be regulated by tension, which will be tested directly by pushing on chromosomes with a micromanipulation needle to relax the tension and allow switching to occur. The motors dynein and CENP-E are present at kinetochores when chromosomes begin to move but are later lost from the chromosomes. The possible uses for such transitory kinetochore motors will be tested. The common errors in chromosome distribution are of two sorts, and tension is involved in avoiding both of them. Avoiding errors of the first sort depends on an anchorage of chromosomes to the spindle that is sensitive to tension. The possibility that the poles are the sensitive site will be tested by micromanipulation. Errors of the second sort are avoided by a checkpoint that detects errors and delays the completion of mitosis. Tension-sensitive kinetochore protein phosphorylation may be the signal to the checkpoint. Tension certainly causes kinetochore dephosphorylation, but the effect may be direct (deformation of some component) or indirect (tension increases the number of microtubules, which may lead to dephosphorylation). This ambiguity will be resolved by creating a situation in which tension can be manipulated yet does not increase the number of microtubules. The effect of tension on the structure of the kinetochore and its components will be explored by combining micromanipulation to vary the tension force with electron microscopy to view the consequences. Kinetochores will be reconstructed by threedimensional tomography. The ultimate goal is to understand how tension, by altering structure, can lead to chemical changes such as dephosphorylation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ANALYSIS OF DSCAM BINDING PROPERTIES Principal Investigator & Institution: Flanagan, John J. Biological Chemistry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2002; Project Start 30-SEP-2002
22 Down Syndrome
Summary: (provided by applicant): Down syndrome is molecularly characterized by a trisomy of chromosome 21, which results phenotypically in malformations of the neuroanatomy and malfunctions in neurochemistry. The founding member of the Down Syndrome Cell Adhesion Molecule (Dscam) family was isolated through a direct screen of a region of chromosome 21. Recently, a new member of the Dscam family, Dsam-1, was identified in Drosophila and statistically exists in over 30,000 isoforms due to alternative splicing of four variable exons. It was shown to be necessary for proper development of the Drosophila central nervous system,and was identified as an axon guidance receptor. Following the discovery of Dscam-1, three new members of the family have been identified in Drosophila. Since the Dscam molecules belong to the immunoglobulin (Ig) superfamily of cell adhesion molecules, they have the potential to act as homo/heterophilic receptors. To identify the molecular function of Dscam-1 and its paralogues, stable cell lines will be constructed expressing one of the four family members. These cell lines will be tested for homo/heterophilic cell adhesion using a standard cell adhesion assay. Briefly, cells will be incubated in suspension either with cells expressing the same Dscam receptor or a different one. The cells will be differentially labeled with lipophilic dyes and checked for aggregation using confocal microscopy. Dscam receptors may also interact in cis (on the same cell surface). This will be tested through transient transfection of one receptor into a stable line expressing another. Co-immunoprecipitation experiments will be done to identify interactions between the two receptors. All possible combinations will be tested. These experiments will begin to elucidate the specificity of the Dscam receptors for each other and their role in axon guidance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: AXON GIUDANCE AND TARGETING IN DROSOPHILA Principal Investigator & Institution: Zipursky, S L. Professor; Biological Chemistry; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): Dscam is an axon guidance receptor that is required for the formation of neuronal connections in the Drosophila nervous system. Dscam loss-of-function phenotypes have been characterized in detail for an embryonic nerve called Bolwig's nerve (BN). Phenotypic studies of Dscam mutants suggest that Dscam protein is critical for mediating a short-range interaction between BN and an intermediate target. Dscam also is required for the specification of other connections in the developing embryo. Dscam protein contains 10 Ig repeats, 6 fibronectin type III repeats, a single transmembrane segment and a cytoplasmic tail with multiple binding sites for the Dock adapter protein, a signaling component connecting Dscam to actin cytoskeletal regulators. Alternative splicing of Dscam may lead to more than 38,000 forms of the receptor. These receptors share the same domain structure, but differ in amino acid sequence in 4 different domains. Three of the Ig domains and the transmembrane domain are variable. This variability reflects the use of alternative exons. In this proposal, the specific form of Dscam expressed in BN will be determined using RT-PCR. Transgene rescue experiments will be used to verify that this form is functional in BN. Transgenes containing different variable domains will be tested for function by targeted expression in BN. Additional experiments will be directed towards determining the pattern of expression of Dscam isoforms in the developing embryo and the developing eye imaginal disc using both in situ hybridization and RT-PCR techniques. These studies will form the foundation for determining whether different
Studies 23
Dscam isoforms contribute to a molecular code for axon guidance and targeting. As Drosophila Dscam is structurally related to a human gene implicated in Down Syndrome, the studies described in this grant may provide insights into the abnormalities in brain development in Down Syndrome patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL ANALYSIS OF A MOUSE MODEL OF DOWN SYNDROME Principal Investigator & Institution: Crnic, Linda S.; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001 Summary: 6The Ts65Dn mouse model of Down syndrome has demonstrated as behavioral phenotype consistent with aspects of the human phenotype of DS. The aims of this proposal are first to continue to determine the behavioral phenotype of this interesting model and second to begin to determine the mechanisms by which overexpressed genes produce the neural and behavioral phenotype. Because DS is a complex disorder, no one brain region is responsible for the cognitive phenotype. Similarly, in this Ts65Dn model, multiple brain regions are implicated by the findings to date, namely the prefrontal cortex, hippocampus, cerebellum and perhaps amygdala. Understanding how deficits in these multiple regions interact to produce the DS phenotype will require a thorough exploration of the behavioral phenotype. We will use contextual and cued fear conditioning, skilled reaching, chaining behavior, reference and working memory, delayed and alternation and a range of eyeblink conditioning paradigms. Our approaches in this aim have from the start been guided by the research and theorizing of our colleagues (Pennington and Nadel) on Project 8. In the new grant period, we have designed experiments in parallel, and in future will be able to make use of their findings with humans to design tests for the animal models. In addition, hypothesis about neural systems involved in DS that derive from the human work can be tested in animals. The hypothesis to be tested regarding neural involvement in DS is that basal forebrain and medial septal cholinergic neurons are involved in the prefrontal and hippocampal deficits in this mouse model. This will be testing by manipulating these cholinergic systems with a well-established prenatal choline supplementation and examining number and size of cholinergic neurons and dendritic spins on hippocampal and cortical neurons. The role of the over production of interferon receptors in the cholinergic phenotype will be tested by crossing the Ts65Dn mice with knockout mice for these receptors to normalize their copy number. In addition, we will make use of transgenic and knockout mice produced by other projects that can be used to determine the role of other individual genes and gene regions in the cognitive phenotype of DS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CEREBRAL GLUCOSE METABOLISM IN DOWN SYNDROME Principal Investigator & Institution: Haier, Richard J. Professor; Pediatrics; University of California Irvine Campus Dr Irvine, CA 92697 Timing: Fiscal Year 2001; Project Start 20-JUL-1999; Project End 30-JUN-2004 Summary: This project will use PET to determine the location and sequence of cerebral glucose metabolic changes as dementia develops in adults with Down Syndrome (DS). Based on the sequencing of brain lesions found in Alzheimer's Disease (AD) and a model proposed by Braak and Braak (1997), we hypothesize that: 1) as dementia begins in DS, the earliest brain changes will be glucose metabolic rate (GMR) decreases in basal
24 Down Syndrome
neocortex or temporal- entorhinal cortical areas and 2) as dementia increases, hippocampal formation areas will show the greatest GMR decreases before frontal and occipital cortex decreases occur. We will examine 20 older non-demented DS patients already entered into the DS Core of the UCI Alzheimer's Disease Research Center and now at risk for dementia based on age (over 35 years old) and impairment scores. Each will receive a PET/FDG scan and neuropsychological assessment once a year for up to five years. A comparison group of mild probable AD patients (n=20) already entered into the Clinical Core also will be studied for five years as will a group of age and sex matched normal controls (n=15). All PET scans will be done with a simple cognitive activation (the Continuous Performance Test of attention) with groups matched on performance. PET and co-registered MRI data will be analyzed using regions-of-interest, SPM96, and other morphing and multivariate techniques. The analyses will include group comparisons of GMR over time in selected brain areas using accelerated growth curve techniques, determining functional relationships among brain areas selected a priori within groups using correlations, and person by person analyses to examine idiographic GMR patterns. We will also compare GMR in ApoE4- defined subgroups of the DS and AD subjects. This project will be unique in combining functional brain imaging using cognitive activation and a 5 year longitudinal design in DS and AD adults as dementia develops. These data will provide important information for the timing of treatment interventions and may aid in early detection of dementia and the classification of DS subtypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITIVE FUNCTION IN AUTISM Principal Investigator & Institution: Ozonoff, Sally; Associate Professor; University of Utah 200 S University St Salt Lake City, UT 84112 Timing: Fiscal Year 2001 Summary: Project II focuses on cognitive variables that may be part of the extended phenotype present in first-degree relatives of individuals with autism. Specifically, this project will focus on the executive function abilities of family members of autistic probands. Initial cognitive studies of parents and siblings focused on general impairments (e.g., mental retardation, learning disabilities), providing mixed evidence for a cognitive endophenotype. More recent investigations focusing on specific cognitive impairments that may aggregate in the families of autistic probands have been more promising, however. Project II concentrates on the integrity of one specific set of neuropsychological processes, executive functions, in family members of autistic probands. To examine whether executive deficits are stratified as a function of proband intellectual level, performance of parents/siblings of non-retarded autistic individuals will be compared with parents/siblings of children with learning disabilities (matched on IQ to autistic probands), while parents/siblings of mentally retarded autistic children will be compared to parents/siblings of probands with Down Syndrome (again matched on IQ to autistic subjects). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITIVE STRENGTHS AND WEAKNESSES IN DOWNS SYNDROME Principal Investigator & Institution: Fidler, Deborah J. Human Develmt & Family Studies; Colorado State University Fort Collins, CO 80523 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005
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Summary: (Provided by Applicant): For individuals with Down syndrome, the most common genetic mental retardation syndrome, research is converging on a cognitive profile consisting of poor verbal working memory and relatively stronger visuo-spatial processing. The implications of this research point to changes in the way children with Down syndrome are taught. Yet this information has remained relatively under-utilized by practitioners, possibly because the visuo-spatial processing relative strength remains poorly understood. In this application, the investigator proposes to: in Specific Aim 1, describe the strengths and weaknesses within the visuo-spatial relative strength in Down syndrome; and in Specific Aim 2, explore the relationship between performance on domains within visuo-spatial processing and other domains of processing (i.e. verbal working memory, auditory processing, expressive vocabulary, reading/decoding, logic). In subsequent research endeavors, the investigator also plans to identify strategies for improving auditory-dependent outcomes in Down syndrome (such as language acquisition) through the relative strength in visuo-spatial processing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COGNITIVE-BRAIN PHENOTYPING OF ATYPICAL CHINESE CHILDREN Principal Investigator & Institution: Karmiloff-Smith, Annette; U of L University College London University College London London, Timing: Fiscal Year 2003; Project Start 28-SEP-2003; Project End 28-FEB-2005 Summary: (provided by applicant): The present proposal describes a series of planning activities to develop an international collaborative program of research on cognitive and brain phenotypes of mentally retarded Chinese children with genetic disorders. Specifically, an international team of medical, psychological, genetic, and computational researchers from P.R. China, the United Kingdom, the United States, and Canada will collaborate to study Chinese children with Fragile-X syndrome (FXS), Williams syndrome (WS), and Down syndrome (DS). The specific aims of the present research planning proposal are:(1) To assess the existing research infrastructure at the Chinese institution (Zhejiang University) for conducting the proposed research activities, (2) To enhance the research capacities of our Chinese research team through workshops and short-term training; (3) To conduct pilot studies that (a) test the feasibility of a computer-assisted 3D photography-based system for identifying a large population of mentally retarded children whose facial dysmorphology may suggest FXS, WS or DS and verify such identifications by genetic tests, (b) translate, adapt, and pilot-test procedures developed by the researchers in UK, US, and Canada to assess children with genetic disorders in terms of their abilities in the areas of language, executive function, and faces and visual-spatial information processing, and compare the Chinese children's cognitive profiles with the existing profiles of affected Western children; (c) use eventrelated potential techniques to examine the neuro-physiological correlates of a small group of the Chinese children with WS, FXS, and DS when they process language and face-spatial information, and compare the results with those obtained with the existing samples of affected Western children. Based on the outcome of 1,2, and 3, the international interdisciplinary team will develop a R01 research proposal that will systematically examine cognitive and brain functions or dysfunctions of Chinese children with Williams, Fragile-X, and Down syndromes from infancy to middle childhood. Our long-term goal is to chart the developmental trajectories of cognitive and brain development in children with genetic disorders, to understand the interaction between genetic abnormality and neuro-cognitive development in different socio-
26 Down Syndrome
cultural contexts, and to provide information for the creation of syndrome-specific and, if necessary, culture-specific intervention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--LANGUAGE AND COGNITION Principal Investigator & Institution: Reilly, Judy S. Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 16-SEP-1985; Project End 31-JUL-2006 Summary: The primary function of Core C is to chart the developmental trajectories through adolescence of language, discourse, attention, spatial cognition, memory and executive function in both normally developing and experimental populations. The Core organization allows us to maximize the efficiency of testing and ensure the smooth flow of information regarding children's testing between the Projects and Cores. It also serves to enhance the consistency, reliability and validity of data collection across Center populations. Core C will have primary responsibility for testing and tracking all normally developing subjects. The experimental populations are those identified with the Population Projects, and include children with early and late brain damage, Language Impairment, Williams Syndrome, and Down Syndrome, and Down Syndrome. These will be tested in close collaboration with Core C on two sub-batteries: A) Longitudinal, off-line: Language, Discourse, Spatial Cognition, Memory, Executive Function; B) Cross-sectional, on-line: Language, Attention and Spatial Cognition. The first sub-battery includes measures to assess later language development, specifically metalinguistic and discourse abilities. By assessing linguistic performance in isolation and in discourse, we address issues of linguistic knowledge versus performance. Using the CHILDES system, Core C will transcribe and code all elicited spoken and written language data. The Attention and Spatial Cognition, Memory and Executive Function Battery includes measures to assess various levels of non-linguistic processing: visual and auditory attention; hemispatial neglect, spatial cognition, verbal and spatial memory, and executive function. These data will permit us to identify association and dissociations within and across the domains of linguistic and non- linguistic cognition. The on-line tasks of Testing Battery B are directly yoked to the neuro-imaging studies (FMRI) and the the ERP studies. The studies outlined in Core C build on our previous research and introduce new lines of inquiry that will inform our understanding of later development in both normal and atypical populations. This new core will centralize our resources and provide a clearly-defined forum for the discussion and investigation of cross-population and investigation of cross-population hypotheses with respect to the development and integration of these basic cognitive systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--TISSUE CULTURE AND MONOCLONAL ANTIBODIES Principal Investigator & Institution: Michaelis, Mary L. Professor; University of Kansas Lawrence Lawrence, KS 66045 Timing: Fiscal Year 2001; Project Start 01-AUG-1991; Project End 30-JUN-2006 Summary: Investigations into the cellular and molecular mechanisms that lead to abnormalities associated with developmental disabilities and mental retardation are increasingly being carried out with in vitro model systems such as cell cultures, including cells transfected with foreign genes and cells derived from transgenic and knockout mice. Advances in understanding the mechanisms for the biochemical pathology of diseases that lead to mental retardation, such as Down syndrome or the
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mucopolysaccharidoses, have been critically dependent upon the development of techniques for studying the altered cellular and biochemical milieu in isolated cell culture systems. In addition, state-of- the-art research in developmental biology frequently requires that investigators develop unique biological reagents such as polyclonal and monoclonal antibodies, various types of nucleotide probes, and constructs for transfection of foreign genes into cells. The Tissue Culture/Monoclonal Antibodies Laboratory (TCMAC) has facilitated the research of several of the Kansas MRDDRC investigators by providing core facilities and services that enable them to develop, maintain, and characterize numerous cellular model systems for exploring aspects of normal cell growth, signaling pathways that regulate cell viability, and effects of exogenous agents that enhance or disrupt cell growth. The TCMAC Laboratory takes great pride in the many enhancements that have been made in the facility during the past grant period as these improvements enable the lab to provide the highest level of support for MRDDRC investigators. The facility has also successfully developed unique polyclonal and monoclonal antibodies that served the needs of individual investigators. The antibody work done for Robert Palazzo has provided an excellent tool in his efforts to identify critical proteins in the centrosome and monitor changes during the cell cycle. The series of antibodies developed for Elias Michaelis have led to important discoveries regarding protein expression and localization in response to chronic ethanol exposure. Antibodies developed by the facility during the past grant period are currently being utilized at other universities in collaborative studies, and a major company has expressed interested in marketing some of those highly specific and valuable tools so they will be available to scientists on an international level. As the TCMAC looks to the future and means of enhancing the Center's focus on biobehavioral processes, the Core will play an expanding role in studies involving gene transfections, growth of ES cells, and other techniques required to produce transgenic or knockout mice. The TCMAC has been and continues to be a relatively small core, but it has played an extremely important role in attracting new, highly productive scientists to the Center itself and encouraging them to apply their talents to new, highly productive scientists to the Center itself and encouraging them to apply their talents to question related to developmental disabilities. For example, the TCMAC was instrumental in the attracting Rick Dobrowsky, Doug Ruden and Robert Palazzo to the MRDDRC shortly after they joined to KU faculty. This core is likely to continue in this role as the University hires new faculty members in the areas of molecular genetics, bioinformatics and developmental neurobiology. The goal of the TCMAC has been and will continue to be the provision of unique bioreagents, skilled technical support, and state-of-the-art equipment to facilitate and enhance the research of MRDDRC investigators who study molecular events leading to developmental disabilities. The TCMAC will continue to facilitate MRDDRC research at The University of Kansas by: (1) Maintaining a centralized facility that provides a cost-effective alternative to purchase of expensive equipment and services by MRDDRC investigators. (2) Producing and characterizing unique monoclonal/polyclonal antibodies and maintaining hybridoma cell lines for projects requiring a consistent supply of antibodies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--TRANSGENIC MOUSE Principal Investigator & Institution: Brennan, Miles B.; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001
28 Down Syndrome
Summary: The identification of a large fraction of the genes on chromosome 21q by Investigators of this PPG has lead to a number of specific, compelling hypothesis about how trisomy of single genes, and also how trisomy of functionally related sets of genes from chromosome 21q may contribute to aspects of the Down syndrome phenotype. Now we can test these genes singly and in the context of the recently developed moused Ts65Dn model of Down syndrome: with these development it has become possible to test these gene by either "adding" or "subtracting" one or more of these genes from the complement of genes trisomic in Ts65Dn, and assaying for the enhancement or amelioration of Down syndrome-like phenotypes in mutant mice. The purpose of this Core is to coordinate and centralize the production of single gene transgenics and single gene knockout mutants. Our target genes will be those identified by Investigators of this PPG as strong candidates for involvement in the Down syndrome phenotype. Not only will it be more efficient to have one transgenic facility, it will also facilitate standardization of the genetic background and initial analyses of mutant phenotypes. We will produce 5 "over-expressing" transgenic lines per year. In the first years of the grant, these will include over expression of CBS (cystathione beta synthase), RED1 (an RNA editase), GAPBA ( a transcription factor), DS-CAM (a cell adhesion molecule), and CHD-1 (a novel protein expressed in brain). We will make 2 knockouts per year from the region trisomic in Ts65Dn. In the first year, these will include Glur5 (a glutamate receptor subunit) and Gart (a protein with three activities of de novo purine synthesis). The mice produced in this Core will be analyzed both by the collaborating Investigators of the PPG as well as by the Behavior Screening Core (Dr. Crnic). While our initial approach to "over-expression" transgenics is the standard oocyte injection protocol (Hogan et al, 1991) which we have used successfully for Gart and Rfc transgenics, we are cognizant of the artefacts frequently encountered with this approach, e.g. altered transcriptional patterns and insertion site mutations (e.g. Burgess et al, 1995; Perry, et al, 1995). Accordingly, we are investigating the use of the recently developed Cre/lox system (Sauer, 1994) to target single copies of the transgenes to specific sites in the mouse genome, known to be transcriptionally permissive and non-mutagenic (Lasko et al, 1996). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORTICAL SURFACE AREA & THICKNESS IN HEALTH AND DISEASE Principal Investigator & Institution: Barta, Patrick E. Associate Professor; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-JAN-2000; Project End 31-DEC-2004 Summary: We propose to explore the neurobiological basis of Down syndrome, schizophrenia, and bipolar disorders using novel methods for measuring cortical neuroanatomy. We will develop and validate methods for measuring surface area, thickness, and thickness distribution of cortical structures, and use these methods in four subject groups: healthy individuals, and patients with Down syndrome, schizophrenia and bipolar disorder. We hypothesize that surface area and thickness measures will be more informative that conventional volume measures, and that patients with Down syndrome will have global cortical deficits. We believe that specific cortical regions will be affected in schizophrenia (heteromodal cortex) and bipolar disorder (entorhinal cortex). Although we focus here on three diseases, we believe that the methods that we will develop would be useful to researchers studying other diseases too. We plan to make our soDware (written in the JAVA language and thus
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portable to most popular computers including C's, Mac's and Unix-based systems) available on the laboratory's web site. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYSTATHIONINE B SYNTHASE AND ARA C THERAPY FOR LEUKEMIA Principal Investigator & Institution: Taub, Jeffrey W. Pediatrics; Wayne State University 656 W. Kirby Detroit, MI 48202 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: The goal of this project is to better understand the biology of acute myeloid leukemia (AML) in Down syndrome (DS) children related to the association of the chromosome 21-localized gene, cystathionine-beta- synthase (CBS) and response to cytosine arabinoside (ara-C)-based therapy. Childhood AML has the worst prognosis of all major childhood cancers with five year relative survival rates of approximately 37%. In contrast, DS children with AML represent an unique group of leukemia patients in view of having significantly higher event-free survival (EFS) rates (70-100% with relapse rates < 15%) compared to non-DS children when treated with ara-C-based protocols. Thus, identifying the biological basis for the extremely high cure rates of DS AML patients can have very important implications and potentially can lead to improvements in AML therapy for all patients. Our previous results have begun to shed light on the underlying mechanisms responsible for the striking increased EFS in DS AML patients. Our results demonstrating i) significantly increased CBS transcript levels in DS myeloblasts and a correlation with in vitro ara-C sensitivity and ara-CTP generation, ii) dramatic increased in ara-C metabolism to ara-CTP in vitro in leukemia cell lines transfected with the CBS cDNA, associated with increased in vitro and in vivo ara-C sensitivity, and iii) significant differences in frequency of the 844ins68 CBS gene polymorphism in DS myeloblasts, provide compelling evidence of an integral relationship between CBS gene expression and ara-C metabolism. This mechanisms is likely a major factor that accounts for the increased chemotherapy sensitivity and high cure rates of pediatric DS AML patients. This study will continue to examine over novel hypothesis and laboratory observations which bridge basic research (e.g., understanding the transcriptional regulation of CBS, determining the relation of CBS mutations/polymorphisms and ara-C metabolism) and apply this work to translational studies using clinical leukemia samples. These findings may ultimately be applied clinically to improve the treatment and cure of AML. The specific aims of the study are: 1) To characterize the transcriptional regulation of the CBS gene in leukemia cell lines and clinical leukemia samples; 2) To develop CBS-transfected AML cell models and to determine the mechanistic basis for the effects of CBS on ara-C metabolism and sensitivity; 3) To determine the relationships between CBS gene expression and ara-C sensitivities in patient myeloblasts with wild-type CBS and with the T833C, G919A, 844ins68 CBS gene variants. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEFINITION AND DEVELOPMENT OF THE PHENOTYPE IN AUTISM Principal Investigator & Institution: Rogers, Sally J. Professor of Psychiatry; Psychiatry; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001; Project Start 01-JUN-1997; Project End 31-MAY-2002
30 Down Syndrome
Summary: The overall goal of this Program Project is to define more clearly what is both familial and specific in the autism phenotype at three levels of analysis "brain, neuropsychology, and behavior" through a series of converging tests. The Program Project is designed to provide a rigorous set of converging tests of five competing neuropsychological explanations of autism: 1) a basic sensory deficit measured by means of magnetoencephalograph (MEG), 2) a praxis deficit, 3) an affective deficit, 4) an inter-subjectivity deficit, and 5) a deficit in executive functions. The converging tests of the latter four, higher level deficit/s are 1) Does the candidate deficits/appear early in the development of children with autism? (0003) 2) Is the deficit/s specific to autism? (Projects 0002 and 003) 3) Are sib pairs concordant for autism also concordant for the deficit/s? (Project 0002) 4) Is the deficit/s pervasive in the sense that it is part of the familial phenotype? (Project 0002) and 5) Is the deficit/s correlated with the brain phenotype, either at a structural (measured by MRI scans) or functional (measured by MEG) level? To permit this set of converging tests, we are studying the same behaviors and neuropsychological constructs in all the samples across Projects. The samples to be studied are 1) 25 multiplex families with idiopathic autism and 25 Down syndrome control families (Project 0002) 2) 40 adults with idiopathic autism, 40 adults with FXS, 40 adults with developmental disabilities (DD) but neither autism nor FXS, and 40 CA and 30 MA controls (Project 0001); and 3) 25 very young children with idiopathic autism, 25 MA and CA controls with DDs but neither autism nor FXS and 25 typically developing MA controls (Project 0003). In collaboration with Jeanette Holden, we will also test the hypothesis that lowered maternal serum dopamine betahydroxylase (DBH), secondary to allelic differences at the DBH locus, provides a uterine environment which is part of the etiology of autism and autistic features in both idiopathic autism and Fragile X syndrome (FXS). GRNT P01HD354680001 Autism is a devastating developmental disorder with an incidence of approximately 1 in 1,000 live birth. While strongly genetically determined, specific abnormalities remain to be determined, and the clinical picture is sufficiently diffuse to implicate pathology in multiple neural systems. Central to the syndrome is impaired social interaction, a severely restricted range of interests, and abnormalities of attention (a hyper-attentiveness), sensation (usually hyperreactivity). We propose to utilize magnetoencephalographic (MEG) sensory evoked field (EF) data, EEG evoked potential (EP) data, and MRI anatomical data to specifically address early cortical processing of sensory information. We will study 1) 40 high functioning (IQ>50) autistic adults, 2) 40 IQ and age matched FraX patients, 3) 40 age matched MR subjects, and 4) 40 age matched normal adults. We will specifically: 1) Using MEG and EEG, we will quantify reactivity of primary auditory and somatosensory cortex to stimuli of varying intensity; 2) By localizing and quantifying very high frequency (VHF) MEG activity (600 Hz) from primary somato-sensory cortex we will directly measure cortical GABA-ergic inhibitory interneurone activity, which we hypothesize will be deficient in autistic subjects (and correlated with cortical hyperreactivity); 3) Using an MEG auditory EF based goodness of fit metric, we will quantify the ability of autistic subjects to shirt attention from one hemisphere to the other during a binaural auditory oddball task; 4) Using the amplitude of the 100 msec latency auditory EF (termed M100) as a function of auditory interstimulus interval (ISI) we will calculate tau (t), the time constant of the decay of the echoic memory trace, generated in Heschl's gyri. We hypothesize this will be prolonged in autistic subjects, relative to normals, Fra-X or MR groups; 5) Using the EEG EP based metric termed mis-match negativity (MMN) we hypothesize that autistic subjects will demonstrate evidence of an accentuated pre-attentive, automatic cortical feature detection processes; 6) Using and MEG EF metric of auditory cortex MEG alpha suppression during a tonal memory task, we hypothesize that autistic subjects will demonstrate evidence of greater alpha suppression than normals, supporting enhanced should term auditory memory storage,
Studies 31
scanning and retrieval; 7) using high resolution MR images of the brain we will quantify volume and relate MEG EF sources to specific cortical areas to determined is MEG and EEG based functional abnormalities are related to observed anatomical deficits in the cortex generating those signals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHILDREN
DEVELOPMENTAL
PROFILES
OF
WILLIAMS
SYNDROME
Principal Investigator & Institution: Bellugi, Ursula; Research Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 16-SEP-1985; Project End 31-JUL-2006 Summary: William's syndrome (WMS) is a genetically based syndrome that results in a cognitive profile of peaks and valleys of cognitive abilities in the mature state. We investigate the development of this unusual profile in WMS Children in order to provide clues to alternative theories of language, cognition, and brain organization. Contrasting Development of Language and General Cognition in WMS. Importantly, in the development of first words, WMS and Down syndrome (DNS) children are equally delayed, and it is only as grammar emerges that WMS appear to show an increasing advantage over DNS. We will examine both on- line and off-line measures focusing and dissociations between language and other domains, as well as the development of discourse functions. a) The Intersection of Language and Affect in Discourse. We investigate hyperaffectivity and language in developing WMS children, which may set them apart from other Center populations. b) The Dissociation between Language and Spatial Representation in WMS. Because of their severe spatial cognitive deficit, WMS children provide a special opportunity to probe potential between language and spatial representations. Contrasting Development: The Dissociation between Space and Face Processing in WMS. WMS results in a highly specific impairment in spatial construction. In contrast, face processing shows strength across paradigms. Thus, WMS children provide a powerful vehicle for investigating the developmental separability of functions within the visual domain. Brain Organization in the Developing Child with WMS. We will examine the hypothesis that developmental aspects of language and spatial functions in WMS may be mediated by neural systems that differ in major ways from those in normal populations. We also hypothesize that there may be differential dysfunction in the dorsal as opposed to the ventral stream of visual processing in WMS, addressed vial electrophysiological and functional MRI studies. Comparison of the profiles of developing WMS Children and other Center populations can provide insights into issues of the genetic bases of higher cortical functions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIFFERENTIAL GENE EXPRESSION IN DOWN SYNDROME PLACENTAE Principal Investigator & Institution: Gross, Susan J.; Montefiore Medical Center (Bronx, Ny) Bronx, NY 104672490 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004 Summary: Pregnant woman are offered multiple marker serum testing for fetal Down syndrome (DS) in the second trimester as routine standard of care. However, serum markers are only a screening tool and not a diagnostic test. Thus, when patients are screen positive, they are offered amniocentesis to confirm the suspicion of fetal DS. These serum markers are nonspecific for DS and, as a result, this test is burdened with a
32 Down Syndrome
significant false positive and false negative rate. Consequently, the vast majority of patients with a positive test will undergo amniocentesis with the real possibility of fetal loss for an unaffected pregnancy. Our hypothesis is that microarray technology available at our center can by used to isolate differentially expressed genes from DS placentae. Our proposed strategy is to apply this high-throughput method of gene expression analysis to identify gene expression changes in placentae from pregnancies affected with Down syndrome, followed by characterization of these genes and their gene products. These findings will form the basis of a subsequent grant submission that will be directed towards the ultimate goal of our placental research program identification and development of specific protein assays for fetal Down syndrome. The specific aim of this current submission is to determine qualitative or quantitative differences in gene expression between DS and normal placentae using microarray chip technology, which will allow for the screening of thousands of genes at once. Differential expression revealed in the microarray studies will be confirmed by Northern blot analysis. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DIGITAL VIDEO ANALYSIS SYSTEM FOR HOME CAGE BEHAVIOR Principal Investigator & Institution: Liang, Yiqing; Clever Systems, Inc. 1334 Stokley Way Vienna, VA 22182 Timing: Fiscal Year 2001; Project Start 01-JUL-1999; Project End 30-JUN-2003 Summary: There is a critical need for automated phenotyping of mutant mouse models that have grown out of recent advances in molecular biology. We propose to meet this need by developing a system for automated scoring of mouse behavior from video records of undisturbed mice in the home cage. Phase I funding resulted in excellent progress on identifying, tracking, and scoring mouse behavior, resulting in 93.5% accuracy in identifying five postures. Phase II funding is requested to extend this system to the entire behavioral repertoire of the mouse in the home cage and refine the algorithms used to identify, track and score mouse behavior with the aim of producing a marketable prototype product. Algorithms for segmenting mouse, tracking its position, identify its posture and behaviors will be developed. The validity of the results will be determined using comparison with human scoring of behavior. The sensitivity of the system will be explored by comparing the results of the prototype systems' analysis of mouse models of Down syndrome, glutaric acidemia (knock- out model) and over expression of purine metabolism genes (GART transgemic) with existing data from other forms of behavioral analysis. The proposed system will produce a major advance in the analysis of behavior and in the ability of investigators to detect novel phenotypes in genetically altered animals. The system will not only provide quantitative data on mouse behavior throughout the daily cycle, but will present the investigator with video clips of novel behaviors that it cannot identify, thus allowing the investigator to see abnormalities in behavior. The system will be efficient enough to be realized with readily available video and computer hardware. The team assembled for this project consists of computer scientists, experts in mathematical modeling, and an expert in mouse behavior has worked well together in Phase 1 and is uniquely prepared to succeed with this project. PROPOSED COMMERCIAL APPLICATION: This proposed research will not only create enormous benefits for the neuroscience and behavior research community including medical research institutes, universities, pharmaceutical companies, and hospitals and clinics who are conducting behavior study and analysis. But also find applications in the entire area of biology will be interested in the system to help them conduct research in such areas as genetic research, cancel research, HIV
Studies 33
research, etc. It can be applied to human-computer interface and surveillance and monitoring areas. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOWN SYNDROME NEUROGENESIS AND COGNITION--GENES AND FUNCTION Principal Investigator & Institution: Korenberg, Julie R. Professor; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001 Summary: Down Syndrome (DS) is the major recognized cause of genetic mental retardation (MR) and affects the welfare of more than 300,000 individuals in the United States Alone. The brains of individuals with DS, although not grossly abnormal at birth, develop microcephaly with decreased size of the prefrontal cortex and cerebellar vermis, and show characteristic subtle abnormalities that include regression and distortion of the dendritic tree and spines, defective lamination of the cortex, and abnormal synapses. The ultimate goal of the research described in this proposal is to began to define the cause of these defects by elucidating the pathways between genes and cognition in Down syndrome and providing models in which to ameliorate them. In the past 5 years, a powerful arrays of tolls has been developed including chromosome 21 genes, the DS phenotypic map, and mouse models of DS. As a first step in identifying a subset of genes that are critical for the neuroanatomic and functional defects of DS, a consensus region for a part of DS mental retardation was generated by this component, and a dense contiguous array of clones covering more than 4 Mb of two critical regions was constructed, one homologous to MMU16 and the other to MMU10. We have isolated and characterized human and mouse gene homologs from these regions that are expressed in the human brain. These genes include DS-CAM, encoding a novel member of neural cell adhesion molecules, responsible for morphogenesis and function of the vertebrate brain. Expressed specifically in the nervous system, it occupies 10-15% of the entire candidate region, and it is a strong candidate for some subtle structural and cognitive defects of DS; PEP19, a peptide expressed only in the post-natal cerebellum and retina; CHD1, highly expressed in fetal brain and brown fat; hPWP2, a yeast homolog responsible for cell separation;TMEM, a large, ubiquitous transmembrane protein. We propose four aims: I. To characterize chromosome 21 gene expression in the brains of Down syndrome and controls during pre and post-natal development using Northerns, tissue in situ hybridization and immunocytochemistry. Genes will include DS-CAM, CHD1, hPWP2, PEP-19 and TMEM-1. II. To characterize mouse gene expression of human 21 homologues in normal, Ts65Dn and Cre-Lox mice with the appropriate duplications, using immunohistochemistry and tissue in situ hybridization. III. To construct transgenic and knockout mice using chromosome 21 genes expressed in the human brain. IV. To analyze transgenic and knockout mice in Aim III for general and neuroanatomy, gene expression and behavior. These models will provide clues to brain morphogenesis and cognition in DS and in normal developments as well as providing models in which to test strategies for treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DOWN SYNDROME, MITOCHONDRIAL DNA AND OXIDATIVE STRESS Principal Investigator & Institution: Sinha, Santosh K.; Brain Insights, Inc. 17595 Harvard Ave, Ste C-173 Irvine, CA 92612
34 Down Syndrome
Timing: Fiscal Year 2001; Project Start 10-JUL-2000; Project End 30-JUN-2005 Summary: (Verbatim from the Applicant's Abstract) Human chromosome 21 (HC21) harbors genes which is believed to be associated with a number of neurological diseases, including amyotrophic lateral sclerosis (ALS 1), familial Alzheimer disease (FAD), and Down syndrome (DS). Among these, DS constitutes the most common disease resulting from partial or total trisomy of HC21. DS is characterized by a number of pathological consequences the most important of which result in precocious aging often accompanied by signs of Alzheimer disease (AD). Several early observations indicated that a small HC21 segment (Down syndrome critical region or DSCR) containing a restricted number of genetic elements may be responsible for most of the Down symptoms. Other regions of HC21 and even some genes present on heterologous diploid chromosomes may also contribute to the complex phenotype of DS either through compensatory or additive interactions. This is presumed to be especially true for genes which code for antioxidant enzymes and which are dispersed throughout the nuclear genome. This has particular relevance in view of the fact that trisomy of HC21 leads to an overexpression of at least two enzymes which are implicated in the production and metabolism of reactive oxygen species (ROS), viz., superoxide dismutase (SOD I) and carbonyl reductase (CBR). In the absence of compensatory support from other antioxidant genes located on heterologous chromosomes (such as glutathione peroxidase and catalase genes), trisomy of HC21 may lead to an accumulation of highly reactive hydroxyl radicals which could severely damage the functional integrity of the cell. One important consequence of such a situation would be lesions in mitochondrial DNA that is especially vulnerable to oxidative injury. The major goals of the present project are to (A) examine the interactions between some of the the key genes of trisomic CH21 and other chromosomal genes, and (B) to verify if antioxidants such as coenzyme Q, vitamin E and ascorbic acid, individually or in combination, could play a positive role in at least partially restoring the normal functioning of trisomic HC21 cells. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SEGREGATION
DROSOPHILA
GENES
AFFECTING
CHROMOSOME
Principal Investigator & Institution: Goldberg, Michael L. Professor; Molecular Biology and Genetics; Cornell University Ithaca Office of Sponsored Programs Ithaca, NY 14853 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 31-MAR-2005 Summary: (Applicant's Abstract): Mistakes in chromosome segregation during meiosis or mitosis can lead to spontaneous abortion or to abnormalities such as Down syndrome, They have also been implicated in the genetic progressions leading to cancer and aging. Our laboratory studies several genes in Drosophila that are required for proper chromosome segregation. We believe that this organism offers important advantages in genetics, genomics and cytology that provide unique opportunities to investigate chromosome behavior and cell cycle progression during cell division. We first focused on an evolutionarily conserved gene called zwlO. Mutations in zwlO not only disrupt chromosome segregation, but they also prevent the operation of the spindle assembly checkpoint that regulates anaphase onset. The ZW1O protein displays an unusual, dynamic pattern of localization during the cell cycle, moving between chromosomal kinetochores and kinetochore microtubules. We found that this pattern is influenced by bipolar tension across individual chromosomes. We also discovered that ZW1O is part of a large protein complex, one of whose activities is to target the molecular motor dynein to the kinetochore. The first specific aim describes further
Studies 35
investigations on ZW1O.We will use real-time video microscopy to characterize the distribution of a ZW1O-GFP fusion protein during the cell cycle. We will determine which domains of ZW1O are required for various aspects of its intracellular distribution and function. We will analyze double mutant combinations to position ZW1O in the biochemical pathways underlying the spindle checkpoint and other aspects of anaphase onset. We will also test whether all aspects of the zw10 mutant phenotype, including its effects on the spindle checkpoint, are caused by the absence of dynein at the kinetochore. The second specific aim is to characterize biochemically and genetically the large complex of which ZW1O is a part. Preliminary efforts to purify the complex by affinity chromatography have been promising. We will use several techniques to verify the association of candidate proteins with ZW1O. We will then identify these proteins by mass spectrometry, and will determine whether they are subject to post-translational modification. Our ultimate goal is to obtain antibodies against these proteins, as well as mutations in the genes encoding them. The third specific aim will exploit our identification in the previous funding period of a set of new mutations that cause precocious sister chromatid separation, aneuploidy, or metaphase arrest in Drosophila. We will study the phenotypes associated with these mutations in more detail, clone selected mutant genes, and then investigate the intracellular location of the corresponding gene products. Because we are focusing on genes not previously known to function in any aspect of mitosis, we believe the genetic and antibody reagents obtained by the proposed studies will provide a broadened and unique view of the events occurring at anaphase onset. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYRK TRANSGENIC MICE AS A MODEL FOR DOWN SYNDROME Principal Investigator & Institution: D'arcangelo, Gabriella; Pediatrics; Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030 Timing: Fiscal Year 2001; Project Start 01-APR-2000; Project End 31-MAR-2003 Summary: (adapted from applicant's abstract) Down Syndrome is the most common genetic disease associated with mental retardation, affecting about 1 in every 800 live births. The syndrome results from triplication of chromosome 21 or a segment of it, and it includes facial abnormalities, heart disease, increased frequency of leukemia, earlyonset Alzheimer's disease and mental retardation. The latter is associated with decreased neuronal number and reduced complexity of neuronal processes in many regions of the brain. The entire spectrum of Down Syndrome abnormalities likely results from overexpression of several genes located in a critical region on chromosome 21q22.2, and it is thus a complex trait. However, individual aspects of the syndrome may be attributable to one or few genes. Recently, the human homologue of Drosophila minibrain, also known as Dyrk, has been mapped to the Down Syndrome critical region. Mutant minibrain flies have a reduced number of brain cells, suggesting that the mutated gene encodes a protein involved in neurogenesis. Mammalian Dyrks are dual specificity protein kinases with extensinve similarities to Drosophila Minibrain and to the yeast Yak1 protein kinase involved in cell division. Injection of a YAC containing genomic sequences including the Dyrk gene in transgenic mice causes altered neurogenesis and cognitive impairment, suggesting that Dyrk is involved in the brain abnormalities associated with Down Syndrome. To understand whether Dyrk plays a role in the developmental neuropathology underlying the mental retardation aspect of Down Syndrome, the investigators plan to first analyze in detail the normal pattern of expressionand activity of Dyrk in the developing mouse brain. Second, they will create transgenic mice that transiently and specifically express elevated levels of Dyrk in the
36 Down Syndrome
proliferative zone of the developing brain. Finally, they will analyze in detail the brains of these mice to ascertain whether reduction in the number of neuronal cells, or other defects reminiscent of Down Syndrome, have occurred as a result of Dyrk overexpression in the brain during the period of neurogenesis. Their transgenic mice may serve as a novel animal model to investigate the molecular basis of mental retardation in Down Syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EARLY DEVELOPMENT: WILLIAMS OR DOWN SYNDROME CHILDREN Principal Investigator & Institution: Mervis, Carolyn B. Distinguished University Scholar and Pro; Psychological and Brain Sciences; University of Louisville University of Louisville Louisville, KY 40292 Timing: Fiscal Year 2001; Project Start 01-MAR-1993; Project End 31-MAY-2004 Summary: The general objective of the proposed research is to delineate the developmental relations between language and cognition. The research will focus on early linguistic and cognitive development by three groups of children: children with William syndrome, children with Down syndrome, and normally developing children. Previous researchers have argued that children with Williams syndrome have language skills that exceed their cognitive skills, whereas children with Down syndrome have cognitive skills that are more advanced than their language skills; in general, normally developing children have equivalent levels of linguistic and cognitive skills. Because of the differences in the general nature of the relations between language and cognition for the three populations, inclusion of all three in a single study provides a unique opportunity to investigate the universality or non-universality of specific relations among language and cognition. The proposed research consists of a five year longitudinal study with supplemental studies conducted at specific points in development. Both observational and experimental methodologies will be used. There are four specific objectives. First, a series of general and specific relations between language and cognition will be examined. Second, the reference of children's earliest words will be explored, using observational, quasi- experimental, and experimental procedures. Third, the development and use of lexical operating principles by children with mental retardation will be considered. Finally, general issues of development by children with Williams syndrome and Down syndrome will be addressed. The research will have implications both for theoretical models of the relation between language and cognition and for the design of early cognitive and language intervention for children with developmental disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EPIDEMIOLOGY OF DOWN SYNDROME--LEUKEMIA & DOWN SYNDROME Principal Investigator & Institution: Ross, Julie A. Associate Professor; None; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, MN 554552070 Timing: Fiscal Year 2001; Project Start 25-SEP-1997; Project End 30-JUN-2004 Summary: The environmental aetiology of Down syndrome (DS) is largely unknown. DS children are at nearly a 20-fold increased risk of developing leukemia compared to children in the general population. Trisomy 21 is also one of the most common acquired cytogenetic abnormalities in childhood leukemia. Thus, constitutional trisomy 21 may represent a first genetic event in the development of leukemia. Since only 1% of DS
Studies 37
children ever develop leukemia, subsequent environmental exposures could be responsible for frank leukemia in this population. The proposed investigation will include: 1) children with DS, under the age of 19, diagnosed with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML), identified through the CCG; 2) children with DS, under the age of 19, frequency-matched by geographic region, age, and race to DS-leukemia cases; and 3) random-digit dialing (RDD) selected regional controls. The proposed case-control studies will include parental interviews, collection of cytogenetic and morphologic data, and medical record validation. In the first casecontrol study (DS-leukemia compared to DS without leukemia) the plan is to determine whether children with DS and leukemia share similar risk factors reported to be associated with childhood ALL and/or AML including maternal alcohol exposure during pregnancy, specific parental occupational exposures, maternal history of prior fetal loss, preconceptional and in utero exposure to X rays. Other potential risk factors will also be explored that may be unique to this case group, including childhood medical exposures, frequency of exposure to infections, vitamin supplementation, and maternal diet during pregnancy. In the second case-control study (DS compared to normal population), the plan is to investigate potential risk factors for DS, as epidemiologic investigations concerning the environmental aetiology of DS are limited. Specifically, the following risk factors, based on previous study findings, will be addressed: parental occupations and occupational exposures, parental smoking and alcohol use, prior use of specific contraceptives, family history of Alzheimer's disease, and parental preconception exposure to x-rays. The proposed study would utilize resources available through the CCG and would include: 1) 152 DS-leukemia cases diagnosed over a five-year period from 1/1/97 through 12/31/01 by the CCG; 2) 304 frequency-matched DS controls; and 3) 304 frequency matched RDD controls. It is claimed that each case-control study has adequate statistical power to address the hypotheses being explored. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EPIDEMIOLOGY OF MENOPAUSE AND DEMENTIA IN DOWN SYNDROME Principal Investigator & Institution: Schupf, Nicole; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, NY 10314 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: An epidemiologic study is proposed to test the hypothesis that reductions in estrogen, indicated by onset of menopause, are associated with onset of Alzheimer's disease (AD) in women with Down syndrome (DS). We further hypothesize that this association will be stronger in women who are genetically susceptible to AD because they carry the apolipoprotein E (apoE) epsilon4 allele. Prior studies in the general population suggest that declines in estrogen levels following menopause play an important role in the etiology AD and that the presence of the apoE epsilon4 allele is associated with earlier age at onset and increased risk of AD. The relationships between onset of menopause, apoE and onset of AD are difficult to study in women in the general population because of the extended time period between menopause and onset of AD. In contrast, women with DS have a very high risk of AD, with an average age at onset of AD between 50-55 years, 10-15 years earlier than in the general population. Thus, women with DS experience onset of AD more closely in time to onset of menopause than is typical in the general population, providing a unique cohort in which to study the relationship between menopause and AD. We hypothesize that earlier age at menopause will be associated with earlier age at onset of AD. We propose
38 Down Syndrome
a 5-year longitudinal study of incident dementia in 350 women with DS, 45-52 years of age, followed at 18 month intervals. We will ascertain age a menopause by chart review, as menstrual cycles are regularly charted in nursing notes. We will supplement this measure with assays of reproductive hormones at each assessment. We will assess declines in cognitive and adaptive competence indicative of AD using a uniform neuropsychological test battery and neurological examination of those suspected to be affected and a sample of those not suspected, with ascertainment of other medical or psychiatric conditions that might cause dementia. We will use standardized criteria for dementia and the differential diagnosis of AD. We will determine DS karyotypes and apoE genotypes. The results of this study will provide important information about the role of estrogen in the etiology of AD and the optimal strategy for the development of clinical trials of hormone replacement therapy in women with DS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ERP/MRP INDICES OF EARLY DEVELOPMENT IN INFANTS W/DS Principal Investigator & Institution: Hill Karrer, Jennifer; R L Smith Mental Retard Center; University of Kansas Medical Center Msn 1039 Kansas City, KS 66160 Timing: Fiscal Year 2001; Project Start 15-MAR-2000; Project End 28-FEB-2005 Summary: During the first 12 months of development in human infancy, the emergence of cognitive and the emergence of motor skills are interconnected. These skills are subsequently applied to most domains of development, including language. Thus, cognitive and motor skills to be achieved during early infancy serve as an essential based for developmental outcome. However, cognitive, linguistic and gross motor domains express the fewest and least consistent gains actualized through early intervention for individuals with Down syndrome (DS) (Connolly et al., 1993; Gibson and Harris, 1988; Piper et al., 1986). It is the working hypothesis of this project that most phenotypic expressions of DS are first actualized as atypical cognitive and motor development during the first year of life. Accordingly, this research project will investigate brain-behavior relationships during cognition and movement among infants with DS that are 1 to 12months of age. Neural measures of attention, stimulus encoding, learning, memory and movement preparation will be recorded in both cross-sectional and longitudinal studies. Results will, for the first time, provide new knowledge concerning brain-behavior relationships during early cognitive and motor development. A group of infants without known risk of developmental difficulties (matched on age, sex and SES) will serve as a comparison group to provide sensitive examination of neurobehavioral expressions in the dysfunction of the nervous system due to DS genetic status. Moreover, characterization and evaluation of the impact of Trisomy-21 upon cognitive and motor functions will be observed before confounding impacts of language impairments are manifested in the development of an individual with DS. At the conclusion of the 5-year project, application of brain-behavior measures in establishing developmental trajectories of cognitive and motor skills will provide new and sensitive methodologies to assess developmental status and, accordingly, the effectiveness of early intervention Thereafter, application of such techniques may provide the foundation for subsequent specialization and refinement of early intervention, particularly with respect to cognitive and motor abilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies 39
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Project Title: SYNDROME
EXERCISE
ADHERENCE
AMONG
ADULTS
WITH
DOWN
Principal Investigator & Institution: Heller, Tamar; University of Illinois at Chicago 1737 West Polk Street Chicago, IL 60612 Timing: Fiscal Year 2001 Summary: Project aims are a) to test the efficacy of a physical exercise program for adults with Down syndrome and b) to test the applicability of the transtheoretical model and social cognitive theory for predicting long- term adherence to enhanced physical activity in this population. It will also test the effects of a health promotion program on their physiological, adaptive behavior, and psychosocial outcomes. The design includes three randomized groups (n=36 per group): control and two intervention groups. Both intervention groups will received a 12-week center-based group exercise and education program offered at the Institute on Disability and Human Development's Center on Health Promotions for Persons with Disabilities. Only one of the intervention groups will receive the caregiver education programs. The project objectives are the following: 1. Test the efficacy of the exercise and education program for older adults with Down syndrome immediately following the program and in four six month intervals after the program is completed. The Exercise program is geared to increase cardiorespiratory fitness, muscle strength, and endurance. The education program for the adults with Down syndrome aims to increase knowledge of exercise benefits and to increase perceived exercise self-efficacy. 2. Assess the long-term benefits of a caregiver (family or vocational and residential staff) education training program geared to help caregivers support adherence to an exercise program. Outcomes assessed to four six month intervals following the program includes exercise adherence, physiological functioning, adaptive functioning, and psychosocial functions of the adult with Down syndrome. 3. Determine predictor variables associated with exercise adherence in the short and longer term (immediately after the training and in four six month intervals after the training)> Predictor variables include level of disability, age, type of residence, and exercise decisional balance (balance of perceived gains and losses and exercise self-efficacy of the adult with Down syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EXPLORING HIPPOCAMPAL FUNCTION IN DOWNS SYNDROME Principal Investigator & Institution: Stedron, Jennifer M. Psychology; University of Denver Box 101562 Denver, CO 80208 Timing: Fiscal Year 2002; Project Start 08-JAN-2002 Summary: (provided by applicant): The proposed research is designed to assess hippocampal function, as characterized by a computational theory of the hippocampus, in children with Down syndrome (DS). The tasks used to assess function are motivated by the hypothesis that the hippocampus is best distinguished as a fast encoder of conjunctive stimuli. This fast, conjunctive theory is supported by both behavioral evidence and a neural network model that incorporates known properties of hippocampal neuroanatomy and physiology. It is hypothesized that a new, hippocampal version of the Eyeblink Classical Conditioning Task (HECC) designed for the proposed studies, will isolate hippocampal function in accordance with the theory and thus is well-suited to assess children with DS. While both toddlers and adolescents with DS and DS mouse models have shown deficits in various tasks thought to tap hippocampal function, these results may be misleading because past tasks also heavily recruit other brain areas that may be impaired in DS, such as the prefrontal cortex or
40 Down Syndrome
areas related to expressive language. Thus, the HECC will provide more conclusive evidence concerning hippocampal function in this population. It is hypothesized that children with DS and a control group will perform similarly on a delay version of the Eyeblink Classical Conditioning Task (DECC) that taps cerebellar function, but will show performance differences on the HECC. In addition, an analysis of the hypothesized performance deficits will be conducted through a neural network model that incorporates neuroanatomical and physiological abnormalities known to be present in DS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAMILIAL PHENOTYPE IN AUTISM Principal Investigator & Institution: Landa, Rebecca; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, CO 800450508 Timing: Fiscal Year 2001 Summary: The overall goal of this project is to test both what is familial and what is specific about the idiopathic autism phenotype (IAP) at two levels of analysis: the symptom and neuropsychological levels. Previous research has identified social and/or language abnormalities in non-autistic first- degree relatives of probands with autism, which is referred to her as the Familial Autism Phenotype (FAP). This Project builds on that previous work and will specify in more detail the nature of the language abnormality in the FAP. However, neither the full range of symptoms nor all the underlying neuropsychological deficits founds in the IAP have been tested in nonautistic relatives, so that both the boundaries of the FAP and its similarity to the IAP remain unclear. It is also unclear which aspects of the FAP and the IAP are specific to autism and not found in other, even closely related developmental disabilities. This project will attempt to close these gaps in existing knowledge by comparing first degree relatives of autistic sib pairs with 1) first degree relatives of Down syndrome (DS) children, 2) females with fragile X syndrome (FXS) from Project III. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAMILY EFFECTS ON SOCIAL OUTCOMES FOR CHILDREN WITH MR Principal Investigator & Institution: Floyd, Frank J. Professor of Psychology; Psychology; Georgia State University University Plaza Atlanta, GA 30303 Timing: Fiscal Year 2001; Project Start 24-SEP-1998; Project End 31-MAY-2003 Summary: Children with mental retardation experience social rejection and isolation; however, there is little information about how families can facilitate their children's social competence and social participation out of the home. This investigation will examine family facilitation of social outcomes in two groups of school age children with mild and moderate mental retardation: a representative sample who do not have Down syndrome (n=60), and a group of children with Down syndrome (n=60). Two comparison groups of school age children also will be evaluated: families of children with learning disabilities (n=60) who are at high risk for social rejection and families of typically developing children (n=60). Three forms of family facilitation will be investigated: indirect facilitation through family interactions that either teach and promote social competencies or lead to social deficiencies, coping assistance strategies to help children manage social problems and direct facilitation through active orchestration of children's social activities. The study will evaluate mothers and fathers and siblings roles in family facilitation using in-home observations and semi-structured
Studies 41
interviews with families. Social competence for the target child will be comprehensively evaluated with observations and parent, teacher, and child reports of social behaviors and adjustment at home and at school. Multiple informants will report on social participation and peer relationships and the children's social-cognitive functioning will be directly assessed. The investigation will employ an overlapping cohort design to evaluate longitudinal changes in family facilitation processes, children's social outcomes, and the associations among these factors. Initial assessments will be conducted when the children are 8 to 10 years old, and all children will be followed through age 11. The families will complete yearly follow-up sessions for 2 to 3 years, and the children's social behaviors and experiences at school will be assessed at 6 month intervals. Hierarchical linear modeling will be used to evaluate linear and non-linear growth trends at the individual and group level, and will examine group differences in both the slope and the shape of changes across time. The analyses will examine hypotheses regarding three general mechanisms which propose that a) the quality of family interactions will influence children's social skills and behavioral adjustment, which in turn will influence their social outcomes; b) both family interactions and family assistance in coping with social rejection will influence the children's social-cognitive functioning; and c) direct efforts by families to arrange and monitor peer activities will be important techniques to promote social participation and acquisition of social skills for children who have disabilities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAMILY DIMENSIONS
EXPERIENCE
OF
GENETIC
TESTING:
ETHICAL
Principal Investigator & Institution: Vanriper, Marcia L. None; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-AUG-2003 Summary: (from applicant's description) Genetic testing is becoming more widely applied. Nurses will be offering, reporting results, and interpreting genetic tests to families; in addition they will be caring for families dealing with the complex personal, social, and ethical issues associated with genetic testing. There is little research available to guide practice in this area. The candidate proposes a study combining qualitative and quantitative methods to explore how families define, manage, and reason about the ethical issues that emerge during four different types of genetic testing (triple marker screening for Down syndrome, carrier testing for cystic fibrosis, mutation analysis for Huntington disease [HD], and BRCA1 testing for cancer risk). The Family Management Style (FMS) Model will guide the study. There are 6 specific aims. Numbers 1 and 2 are related to family member's definition, management, and reasoning about moral issues. Number 3 involves comparison of family members from the same family. Number 4 concerns how responses differ according to the type of test. Number 5 involves description of distinct family management styles of decision-making. Numbers 6 is designed to explore management style and psychological well being of the tested family member. Participants will be members of 40 families (10 from each of the four types of testing). Inclusion criteria include having undergone one of the 4 selected genetic tests or being a family member of such a person. The term family is defined and members are self identified. Families will only be studied if both the tested member and at least one other family member agree to participate. An interview guide will be developed based on the FMS model, the literature on genetic testing, clinical experience of the investigator, and Rest's work on moral judgement. The Defining Issues Test (DIT) will be used to assess patterns of moral reasoning. The tested family member also will
42 Down Syndrome
complete Ryff's measure of psychologica well being, and the POMS to measure psychological distress. Data will be analyzed following guidelines and techniques of Knafl and Ayers, Knafl and Webster, Miles and Huberman, and Patton. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FEASIBILITY OF PRENATAL SCREENING FOR SLO SYNDROME Principal Investigator & Institution: Haddow, James E. Vice President and Medical Director; Foundation for Blood Research Box 190, 69 Rte 1 Scarborough, ME 04070 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: This study aims to evaluate the efficacy of routinely identifying Smith-LemliOpitz Syndrome (SLOS) prenatally. This serious inherited metabolic disorder (birth prevalence 1:20,000) is characterized by moderate to severe mental retardation and congenital anomalies. Two circumstances now make it possible to carry out the proposed intervention trial. First, the cause of SLOS is now known to be a defect in the conversion of 7-dehydrocholesterol to cholesterol. This discovery makes it possible to confirm the diagnosis biochemically by measuring cholesterol precursors in the serum of affected individuals and in amniotic fluid. Secondly, the array of maternal serum analytes currently measured routinely to screen for Down syndrome in 2,000,000 U.S. pregnancies annually includes unconjugated estriol (uE3). This analyte requires cholesterol as a precursor, and its concentration in maternal serum is lower when the fetus has SLOS. The major barrier to identifying SLOS prenatally is the absence of sound screening methodology that takes into account the detection rate, the false positive rate, and the prevalence. The investigators have developed a model, based on actual data from SLOS pregnancies, and propose to test it in 1,000,000 pregnancies in which maternal serum uE3 (and other) measurements are currently being done routinely. The screening false positive rate is projected to be 0.2 percent, the detection rate 57 percent, and the odds of being affected given a positive result 1:70. These rates all compare favorably with routine prenatal screening tests. Diagnostic testing in amniotic fluid is highly reliable and will correctly identify the affected and unaffected pregnancies. In the proposed trial, the investigators will introduce this SLOS model into several major U.S. prenatal screening centers, and develop informational materials for both physicians and patients. Diagnostic testing will be provided by participating expert laboratories. It will also be possible, for the first time, to determine whether SLOS diagnostic studies can be carried out in maternal urine, rather than amniotic fluid, thereby avoiding invasive procedures. The study will also aid in refining prevalence estimates by race and ethnicity, and will determine whether several rare disorders in the cholesterol biosynthetic pathway would be detectable. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUNCTION OF MAMMALIAN SINGLE MINDED GENES, SIM1 AND SIM2 Principal Investigator & Institution: Fan, Chen-Ming; Carnegie Institution of Washington, Dc 1530 P St Nw Washington, DC 20005 Timing: Fiscal Year 2001; Project Start 01-MAY-1998; Project End 30-APR-2003 Summary: (adapted from investigator's abstract): The goal of this proposal is to investigate the function of mammalian Sim1 and Sim2 genes using transgenic mouse models. Sim1 and Sim2 are homologues of the Drosophila sim (singleminded) gene. In the fly, sim plays essential roles in the development of the central nervous system. Preliminary studies of the mouse Sim genes strongly suggest evolutionarily conserved
Studies 43
functions. The SIM proteins contain conserved sequence motif termed the PAS domain, which is hared by several environmental sensor proteins such as the Dioxin receptor, the Hypoxia Inducible Factor, the Drosophila circadian rhythm regulator Per, and the B. subtilis sporulation regulator KinA. This information strongly indicated that SIMs may also respond to specific environmental signals via their PAS domains. This proposal includes the following aims: 1) documenting the expression patterns of Sim1 and Sim2 in detail; 2) establishing mouse models lacking Sim1 and Sim2 gene function by homologous recombination and characterizing mutant phenotypes in order to assess the normal function of these genes, and 3) identifying possible small molecule ligands that modulate the function of Sim1 and Sim2. Importantly, the mouse Sim2 gene is located in the syntenic human Down syndrome critical region. Furthermore, mutant mice lacking Sim1 display neurological disorders that may relate to multiple sclerosis. Exploration and identification of possible small ligands that regulate Sim1 and Sim2 function will be the first step towards developing methods to alter their gene activities in vivo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENE ISOLATION AND FUNCTIONAL ANALYSIS OF 21Q11-21 RELATING TO DOWN SYNDROME Principal Investigator & Institution: Kao, Fa-Ten; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001 Summary: The overall aim of this sub-project focuses on gene isolation and molecular analysis of the proximal half of the long arm of human chromosome 21 including 21q1121, a region under-exploited but associated with mental retardation of individuals with Down Syndrome. The specific objectives are: (1) Isolation, characterization and sequencing of unique sequence microclones from microdissection libraries constructed specifically for the 21q11-21 region; (2) Homology analysis between the unique copy microclones and know genes or cDNAs; (3) refined regional mapping of microclones within 21q11-21; (4) comparative mapping between 21q11-21 and the mouse genome; (5)methylation analysis of 21q11-21; (6) chromatin condensation analysis of 21q11-21 during interphase; (7) isolation and characterization of CDNAS from 21q11-21; (8) gene expression analysis using demetylation strategies; (9) study of the genomic structure and organization of 21q11-21 relating to its function and regulation; (1) analysis of genes and cDNAs identified in 21q11-21 for possible involvement in cognitive-neural developmental deficits in mental retardation. Promising progress towards most of these objectives have already been made to demonstrate that the 21q11-21 region indeed have genes which may be important to Down syndrome. These studies also showed that 21q11-21 has unique structures which may be crucial to the regulation of the genes residing in this region. Thus, gene isolation and better understanding of the regulation and expression of 21q11-21 should be important to the unraveling of the etiology of mental retardation in Down syndrome and for possible early intervention of this devastating pathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENES FOR KERATOCONUS AND OCULAR FEATURES IN TRISOMY 21 Principal Investigator & Institution: Bergwerk, Katherine L.; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, CA 90048 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2005
44 Down Syndrome
Summary: This application for a Mentored Patient-Oriented Clinical Scientist Development Award (K23) seeks support for Katherine Bergwerk, MD, a staff ophthalmologist at Cedars-Sinai Medical Center (CSMC), who recently completed a Clinical fellowship in Ophthalmic Genetics at CSMC and U.C.L.A.'s Jules Stein Eye institute. Under the mentorship of Julie R. Korenberg, MD, PhD, and Yaron S. Rabinowitz, MD, Dr. Bergwerk will pursue investigation of gene loci for keratoconus and other ocular abnormalities in patients with partial trisomies and tetrasomies of chromosome 21. Identifying a gene for keratoconus may allow for early detection of the disease and may enable medical therapy to be developed to retard its progression. This will obviate the need for the current therapy of multiple complex contact lens fittings or corneal transplantation surgery. Keratoconus is a major cause of visual disability and one of the leading causes for penetrating keratoplasty in the United States. In the process of completing comprehensive ocular examinations on these rare patients for keratoconus, attempts will be made to make genotype-phenotype correlations of other eye abnormalities in patients with Down syndrome. Dr. Rabinowitz is a prominent researcher in the field of ophthalmic genetics, who has established a candidate region for a keratoconus gene locus. This region is a 5.4 centimorgan (cM) region which is 11 cM distal to the centromere on the long arm of chromosome 21 (see appendix A). Review of the literature suggests that keratoconus may occur as much as 300 Xs more commonly in Down syndrome patients than in the general population. Dr. Korenberg is a renowned molecular geneticist who has served on the Human Genome Project for defining genes on Chromosome 21. Her unique population of partial trisomy Down syndrome patients are the ideal group to use in refining a gene locus for keratoconus and to make genotype- phenotype correlations of ocular features of Down syndrome. Under Dr. Rabinowitz and Dr. Korenberg's mentorship and with institutional support from the Divisions of Medical Genetics and Ophthalmology at CSMC, Dr. Bergwerk will further her training in clinical genetic research, and enhance her skills in clinical and molecular genetics. Dr. Bergwerk aspires to achieve her goal of becoming an independent investigator who is capable of solving clinical problems in a research laboratory. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENES, ANEUPLOIDY AND MAMMALIAN DEVELOPMENT Principal Investigator & Institution: Gearhart, John D. Professor; Gynecology and Obstetrics; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001; Project Start 01-APR-1989; Project End 30-JUN-2004 Summary: Down Syndrome is the most common known genetic cause of mental retardation. The major goal of this program is to understand the genetic and biologic bases of mental retardation in Down Syndrome. Building on the increasing large body of information on Down Syndrome, from the genetics to the clinical features, this program utilizes recombinant DNA technology, comparative genetics, and animal models in attempts to identify and characterize the genes involved in the Syndrome, particularly those producing the neurobiological and cognitive deficits. Also, utilizing some of the animal models, neuropharmacological interventions are proposed in attempts to ameliorate the learning and memory deficits that have been demonstrated in these animals. These animal-based efforts will ultimately lead to therapies for the neurobiological and cognitive deficits characteristic of Down Syndrome. Finally, we propose a new study combining cytogenetic, molecular and epidemiological approaches to address factors that may predispose to non-dysfunction of chromosome 21 and the genetic basis of the phenotypic consequences of an additional chromosome 21.
Studies 45
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC MODIFIERS OF ALZHEIMER'S DISEASE ANIMAL MODELS Principal Investigator & Institution: Lamb, Bruce T. Assistant Professor; Case Western Reserve University 10900 Euclid Ave Cleveland, OH 44106 Timing: Fiscal Year 2001 Summary: Alzheimer's disease (AD), the most common cause of dementia in the elderly, is now the fourth major cause of death in the developed world after heart disease, cancer and stroke. AD is strongly influenced by genetics, with current estimates suggesting that greater than 40% of all AD cases are familial (FAD). Genetic investigations have demonstrated that AD is a heterogeneous disorder with several known etiologies including: dosage imbalance for chromosome 21 as occurs in Down syndrome (DS); mutations in the amyloid precursor protein (APP) gene on chromosome 21, the presenilin-1 (PS-1) gene on chromosome 14 and the presenilin-2 (PS-2) gene on chromosome 1 in autosomal dominant early-onset FAD; and inheritance of distinct alpha-2 microglobulin and apolipoprotein E (ApoE) gene alleles on chromosome 12 and 19, respectively, as significant genetic risk factors for late-onset FAD. Additional genetic risk factors for AD are certain to exist. A pathologic hallmark in the brains of individuals with AD is deposits of the beta- amyloid (Abeta) peptide in the parenchyma of amygdala, hippocampus and neocortex. One of the major difficulties in studying the mechanism(s) of Abeta deposition and its impact on AD-related neuropathology, behavior and physiology is the paucity of accurate animal models. To establish an accurate genetic model for AD, we have focused on introducing entire genomic copies of either wild-type (wt) or mutant human APP and PS-1 genes carried on yeast artificial chromosomes (YACs) into the mouse germline and have recently demonstrated that a threshold into the molecular and mechanisms of the disease. The specific aims of the current proposal are to examine the effect of specific human AD genetic risk factors, namely dosage imbalance for genes on chromosome 21 (in the Ts65Dn mouse model of DS) and the various ApoE alleles (in ApoE knock-in mice), across the lifespan of APP YAC transgenic mice on: 1) Localization and timing of Abeta deposition and other structural neuropathology. 2) Learning and memory deficits characteristic of individuals with AD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENETIC RISK FACTORS FOR HYPERHOMOCYSTEINEMIA Principal Investigator & Institution: Gravel, Roy A. Professor of Cell Biology & Anatomy And; University of Calgary 2500 University Dr Nw Calgary, Timing: Fiscal Year 2002; Project Start 01-AUG-1997; Project End 30-NOV-2006 Summary: (provided by applicant): It is now well established that elevated total plasma homocysteine is an independent risk factor for cardiovascular disease and that low folate shows association with increased risk for having a child with neural tube defects. Extrapolating from the central role played by a polymorphism of MTHFR in this process, we set out to clone genes and identify polymorphisms to determine if other genes involved in the metabolism of homocysteine would show such associations. A major outcome was the discovery of a novel enzyme methionine synthase reductase (gene and enzyme symbol, MTRR) required for the activation of cobalamin-dependent methionine synthase (MS). Through these experiments we detected a polymorphism, 66A>G (122M), present at a remarkable - aboutO.5 frequency, that appears to be
46 Down Syndrome
associated with premature coronary artery disease, neural tube defects and Down syndrome. Significant progress included identification of mutations in severely affected patients with MTRR deficiency, modeling the 122M variant in the orthologous E. coli flavodoxin, and development of a mouse model of MTRR deficiency (founder heterozygotes confirmed). We hypothesize that the association of the 122M polymorphism with disease derives from structural and functional disturbances in the variant enzyme with impact on biochemical homeostasis and development. Accordingly, we propose the following specific aims to characterize the mechanism and physiological role of this novel enzyme and polymorphism: (1) Determine the biochemical impact of the 122M mutation in E. coil flavodoxin and humanMTRR. These studies will include biochemical characterization of 122 and M22 MTRR; assessment of FMN binding and domain interactions by 122M flavodoxin; and comparative crystal structure of 122M flavodoxin. (2) Characterize the phenotype of homozygous and heterozygous MTRR knock-out mice to gain understanding of the impact of severe and mild MTRR deficiency on physiology and development. We will examine the expression patterns of MS and MTRR during embryogenesis and in adult tissues by in-situ hybridization, Western blot and tissue immuno-fluorescence; evaluate levels of folate and methionine cycle metabolites in heterozygous and homozygous mutant mice, characterize the general pathology and behavioral phenotype of affected mice; evaluate vascular pathology and function; and explore nutrition-based treatment of homozygous mutant mice. In summary, our study will give a biochemical and physiological face to the impact of 122M on enzyme function, development and disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS OF TURNER SYNDROME--COGNITIVE/PHYSICAL ASPECTS Principal Investigator & Institution: Zinn, Andrew R. Assistant Professor of Internal Medicine; Internal Medicine; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-MAR-1997; Project End 31-JUL-2002 Summary: Turner syndrome is a human genetic disorder involving females who lack all or part of one X chromosome. The principle features are short stature, infertility, and anatomic abnormalities that include webbed neck, congenital heart disease, and renal and skeletal malformations. Selected neurocognitive deficits, including impaired visualspatial abilities, are also characteristic of Turner syndrome, but global developmental delay is uncommon. As a relatively common genetic disorder with well-defined manifestations, Turner syndrome presents the opportunity to investigate genetic factors that influence female physical and cognitive development There is potentially informative genetic and phenotypic variation among Turner syndrome subjects with partial X deletions (partial monosomy X). Careful clinical and molecular characterization of these unusual subjects who represent "experiments of nature" could link individual Turner syndrome phenotypic features to specific X chromosome regions. Similar studies are in progress for Down syndrome and other chromosome disorders. Turner syndrome is an excellent model for such phenotype mapping studies because of its prevalence, the well-characterized phenotype, and the wealth of molecular resources available for the X chromosome. The disorder is also a model for studying genetic aspects of cognition because of the selective nature of neurocognitive deficits and the relative sparing of verbal abilities. This study will examine approximately 80 partial monosomy X subjects. Each subject will have a thorough clinical evaluation and extensive neurocognitive testing to determine the presence or absence of specific Turner
Studies 47
syndrome phenotypic features. Cell lines will be established and used for molecular studies to precisely define the subjects' X deletions. The goal of this study is to define critical regions of the X chromosome for neurocognitive deficits and physical features associated with Turner syndrome. Phenotype mapping of X deletions will be helpful for genetic counseling and for predicting which girls with Turner syndrome are at high risk for learning difficulties; these children and their parents might benefit from extra social, psychological, and educational support. The collection of cell lines will also provide a valuable resource for future studies aimed at identifying specific Turner syndrome genes. Characterization of these genes would provide insight into the pathophysiology of Turner syndrome as well as processes of normal physical and cognitive development. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETICS, MORTALITY AND DEMENTIA IN DOWN SYNDROME Principal Investigator & Institution: Zigman, Warren B. Reasearch Scientist; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, NY 10314 Timing: Fiscal Year 2001; Project Start 16-FEB-1999; Project End 31-JAN-2004 Summary: Down syndrome, one of the most common genetic causes of mental retardation associated with genetic factors, occurs in approximately 1.2 per 1000 live births, is typically caused by a nondisjunction of the 21st chromosome during meiosis resulting in a complete trisomy genotype, although atypical forms occur occasionally. Adults with Down syndrome have benefited from the advances in public health practices that have resulted in a dramatic extension in life expectancy. However, Down syndrome is still characterized by increased mortality rates during later stages of life. Causes of higher mortality rates later in life may be due to a number of factors, two of which are an increased risk for Alzheimer~s disease and an apparent tendency toward premature aging. Aging processes among adults with Down syndrome have been of interest for over 100 years because of the occurrence of the signs and symptoms of Alzheimer~s disease in the population. Indeed, brain tissue of virtually all adults with Down syndrome over 35 to 40 years of age displays significant accumulations of amyloid plaques, historically considered to be a hallmark of Alzheimer's disease neuropathology presumably due to the triplication and over expression of the gene for beta-amyloid precursor protein located on chromosome 21. The genotypic and phenotypic characteristics of the "oldest old" (i.e., 65 and older) adult population with mental retardation due to Down syndrome will be compared to those of their younger peers (also with Down syndrome) in order to identify genetic risk factors associated with survival and the cognitive declines associated with dementia of the Alzheimer~stype. We have been able to identify a group of 100 people with Down syndrome 65 years of age or older. Investigation of this unique group of individualist will allow us to characterize the phenotype of the ~oldest old~ with Down syndrome and identify genetic and health status factors that are associated with extended survival and successful aging on one hand and the development of DAT on the other. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GONADAL PEPTIDE EFFECT ON FEMALE REPRODUCTION-ACTIVINS Principal Investigator & Institution: Lin, Yu-Wai P.; Barry University 11300 Ne 2Nd Ave Miami, FL 33161 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007
48 Down Syndrome
Summary: Folliculogenesis in vertebrates involves the developmental progression from a small primordial follicleto a large preovulatory follicle containing a fully competent oocyte arrested at the second meiotic metaphase by the time of ovulation. This entire process is regulated and coordinated by endocrine hormones such as the pituitary gonadotropins, and locally modulated by steroids and factors (inhibin/activin) acting in an autocrine/paracrine manner. The molecular nature of these factors is only now being elucidated. Gonadal peptides such as inhibin and activin are currently being recognized not only as regulators of the pituitary gonadotropins secretion, but also as multifunctional modulators in the ovary and in the utero-placental unit. In addition to their normal reproductive roles, inhibins and activins have been implicated in gonadal oncogenesis and pathologies of the reproductive system. In this regard, high levels of inhibin B are associated with granulosa cell carcinoma, and high levels of inhibin A are correlated with pre-eclampsia and Down syndrome during pregnancy. The understanding of the relationship of several gonadal peptides to the signals for gonadal function still has many unanswered questions. This proposal is designed to elucidate the molecular mechanisms underlying the expression and the paracrine and autocrine biological activities of inhibin/activin A and B. Although the different inhibin/activin isoforms (A and B) appear to have similar effects in the pituitary, there is also precedent suggesting that they may have distinct physiological roles in different tissues. The availability of recombinant inhibin/activin A and B now gives the possibility to assess the functions of the various inhibin/activin isoforms. In order to implement the above objectives, the following projects will be carried out:: a) Isolation and cloning of the inhibin/activin subunits (alpha,betaA,and betaB) from ovarian tissue, b) Antibodies against the inhibin/activin subunits will be generated to carry out western blot analysis, c) Expression of inhibin/activin subunits during follicle development and during the process of gonadotropic stimulation of oocyte maturation, d) Paracrine (local effect at neighboring cells) and autocrine (local effect in the same cells) biological activities (on steroidogenesis and oocyte maturation) of inhibin/activin A and B will be assessed using in vitro ovarian follicle cultures, to test the hypothesis that the various forms of the gonadal peptides may have distinct physiological roles in the ovary. The proposed research will furnish critically needed information about the molecular dynamics and actions of the inhibin/activin in the ovary. Understanding the physiology of inhibins and activins and the interplay of major endocrine and paracrine mechanisms involved in the ovary is essential to decipher the process of gonadal differentiation in both normal and disease conditions, and may ultimately help in the diagnosis and treatment of reproductive dysfunction in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GRAMMATICAL /INTELLIGIBILITY INTERVENTION--DOWN SYNDROME Principal Investigator & Institution: Camarata, Stephen M. Professor of Hearing and Speech Sciences; Psychology & Human Development; Vanderbilt University 3319 West End Ave. Nashville, TN 372036917 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2004 Summary: (provided by applicant): Children with Down syndrome often display speech-intelligibility and grammatical deficits beyond what would be predicted based upon general cognitive levels. The purpose of the proposed study is two-fold. First, recast intervention techniques that have proven effective in other populations with speech-intelligibility and grammatical deficits will be piloted in children with Down syndrome. Second, mismatched negativity (MMN) and N1 will be measured using ERP
Studies 49
techniques and oral motor functioning as potential predictors of growth during intervention. A total of 12 children will be included in a multiple baseline, multiple probe design during the two year project. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACTS OF PARENTING ADOLESCENTS & ADULTS WITH AUTISM Principal Investigator & Institution: Seltzer, Marsha M. Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 01-FEB-1990; Project End 31-AUG-2005 Summary: This application seeks five years of support to continue the investigators' dual site research involving the impacts of life long parenting for adolescent and adult sons or daughters with mental retardation (MR). The focus of the work shifts in this application to a new population, as a sample of 400 families of adolescents and adults with autism will be studied. The proposed investigation will address four central issues: (1) the manifestation of symptoms of autism among adolescents and adults (both crosssectionally and longitudinally, (2) the effects of the behavioral, communicative, and social functioning of persons with autism on parental well-being (again cross-sectionally and longitudinally), (3) the antecedents and consequences of placement of the person with autism, and (4) the impact of differential diagnostic groups on family well-being. The fourth aim, families of persons with autism will be compared with two previously collected samples of families: one with a son or daughter with Down syndrome, and one with a son or daughter with schizophrenia. These samples, and the data relating to them, are available from previous or ongoing funded work by the current investigative group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LANGUAGE DEVELOPMENT IN DOWN SYNDROME CHILDREN Principal Investigator & Institution: Chapman, Robin S. Professor; Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 01-JUL-1987; Project End 31-DEC-2003 Summary: Children and adolescents with Down syndrome (DS) are reported, variously, to have language skills above (vocabulary comprehension) and below (expressive syntax) their nonverbal mental age; cross-sectional evidence suggests that the deficits increase with age. The goals of the present work are to determine, through longitudinal study, whether the gaps between the cognitive level of children with DS and their expressive and receptive language levels widen with age and to identify acquisition processes associated with variation in language skill with DS children. This competing continuation proposal extends the period of longitudinal study of 5 DS children and adolescents aged 5 to 21 years from two to six years and the number of DS observation points from two to four. It permits a definitive longitudinal test of the cumulative deficit hypothesis and, in doing so, permits an empirical test for an elaborated theory of language production development (Child Talk) that would not be possible in normally developing children, whose cognitive and language skills do not ordinarily diverge widely. Computer analyses of the free speech transcripts will permit a detailed longitudinal description of changes in the syntax, semantics, and pragmatics of spoken language in children with DS over the six year period. Hierarchical linear modeling will be used to evaluate between-s predictors of rates of growth in the language variables. In
50 Down Syndrome
addition, new studies of DS children's ability to narrate and recall novel events, to "fast map" novel word meaning from event and story contexts, and to benefit from prior discourse use of words and sentence structure in utterance formulation will be conducted, elaborating the experimental investigations of narration, vocabulary acquisition, and prior discourse priming on the basis of outcomes in the current grant period. Experimental tasks evaluating comprehension strategies will be added. Performance on all tasks will be compared to three groups of normally developing children statistically matched for 1) nonverbal mental age and SES; 2) language comprehension and SES; and.3) language production and SES. Within the DS group, experimental task performance will be analyzed for variation as a function of cognitive, comprehension, and production skills in a test of the Child Talk model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LINGUISTIC COMMUNICATION AND MENTAL RETARDATION Principal Investigator & Institution: Abbeduto, Leonard J. Professor; Waisman Ctr/Mr & Human Devlmt; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001; Project Start 01-SEP-1987; Project End 30-JUN-2003 Summary: This project will investigate the development of discourse in adolescents who have mental retardation due to Down syndrome (DS) or fragile X syndrome (FXS). Each syndrome is characterized by impairments in the domains of behavioral functioning that support discourse development (e.g., cognition, receptive language) and, thus, individuals with either syndrome are likely to find discourse to be especially challenging. There are also differences in the behavioral phenotypes of DS and FXS, which may lead to different profiles of discourse problems. There are few data on the discourse skills of individuals with DS or FXS and fewer data still on discourse problems that may be specific to one syndrome or the other. The need for such data is especially acute during the adolescent years. During adolescence, preparation begins for adult roles that demand expertise in discourse. This project will examine discourse in adolescents with DS and adolescents with FXS from a model in which discourse is seen to emerge from the collorative activity of people working toward a common goal. This project has three specific aims. This first is to determine (a) whether discourse development is more severely disrupted in these adolescents than expected from their levels of functioning in domains that support discourse development (i.e., cognition, linguistic ability) and (b) whether it is disrupted differently in the two syndromes. The second aim is to (a) identify the ways in which developments of nonverbal cognition, language, social cognition, speech, and hearing contribute to the ability of these adolescents to collaborate effectively and (b) determine whether these domains make different contributions to discourse for DS and FXS. The third aim is to determine what syndrome-specific impairments (i.e. psychopathology and auditory memory problems) contribute to discourse collaboration. Five studies will address these aims. In each, participants will engage in a referential task that is designed to highlight differences between the syndromes. Comparisons with younger, typically developing children will determine the extent to which discourse development is disrupted in each syndrome. Measures will be taken of domains in which there are syndrome-shared impairments. Hierarchial multiple regression will be used to examine the contributions of these domains to the discourse collaboration of the DS and FXS groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LONGITUDINAL LANGUAGE Principal Investigator & Institution: Hart, Betty; University of Kansas Lawrence Lawrence, KS 66045 Timing: Fiscal Year 2001 Summary: The proposed research will examine the contribution of fewer declarative sentences and less frequent conversation to delays in expressive language among children with Down syndrome. Data from more than 10 years of longitudinal observations of communicative development in children with retardation being reared at home will be compare to data from 21/2 years of methodologically-identical observations of typically-developing children learning to talk. Each declarative sentence will be located in each child's data and coded for initiator, turns, shared topic, different and mutual vocabulary, and parent behaviors that may be facilitate learning to converse. The results of the two studies will be the basis for proposing interventions to remediate the deficit in MLU (mean length of utterance) that leads the language skills of children with Down syndrome to lag behind measures of their cognitive functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MECHANISMS OF LEUKEMOGENESIS IN DOWN SYNDROME Principal Investigator & Institution: Crispino, John D. Ben May Institute; University of Chicago 5801 S Ellis Ave Chicago, IL 60637 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: (provided by applicant): Children with Down syndrome (DS) have a 10-20 fold increased risk of developing leukemia, in particular acute megakaryoblastic leukemia (AMKL). While the genetic lesions that promote leukemia in Down syndrome have been largely undefined, we recently demonstrated that leukemic cells from every DS-AMKL patient examined harbor mutations in the essential hematopoietic transcription factor gene GATA1. In every instance, the mutation involved a small insertion or deletion in GATA1 that resulted in a frame-shift and the introduction of a premature stop codon within the sequences encoding the N-terminal activation domain of GATA-1. These mutations prevent the synthesis of the 50-kD full length GATA-1, but not of a 40-kD isoform initiated further downstream, termed GATA-1s. In this application, we propose to study the mechanism of leukemogenesis in patients with GATA1 mutations. Furthermore, we will seek to identify the cooperating factors that are likely contributed by trisomy 21 in Down syndrome AMKL. Specifically, we plan: 1) To determine the incidence and distribution of GATA1 mutations in a greater number of DS-AMKL samples as well as in DNA from patients with DS pre-leukemia, named Transient Myeloproliferative Disorder; 2) To assess whether loss of GATA-1 in conjunction with the mouse equivalent of trisomy 21 can promote leukemogenesis in mice, and further, whether overexpression of GATA-1s can promote immortalization of GATA-1-deficient megakaryocyte progenitors; and 3) To develop a mouse model of DSAMKL by creating mice that will conditionally express only the 40-kD isoform of GATA-1 and breeding them to mice with the murine equivalent of DS. Separately, we will also cross these novel GATA1 mutant mice into the BXH-2 strain of mice to identify genes that cooperate with the GATA1 mutations in leukemia. These studies will likely increase our understanding of how GATA1 mutations contribute to the initiation or progression of leukemia in Down syndrome and may also lead to the identification of novel leukemia disease genes on chromosome 21. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEMORY AND COGNITION IN AGING ADULTS WITH DOWN SYNDROME Principal Investigator & Institution: Devenny, Darlynne A.; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, NY 10314 Timing: Fiscal Year 2001; Project Start 15-JUN-1998; Project End 31-MAY-2003 Summary: Adults with Down syndrome (DS) experience changes in functioning associated with normal aging precociously, and they are at higher risk for developing Alzheimer's disease than their peers with other forms of mental retardation (MR). The first aim of the proposed project is to characterize specific changes in memory and cognitive processing that occur during normal aging and to identify individual differences in vulnerability to early onset of age-associated changes in adults with DS. This project will focus on the study of working and episodic memory, two systems known to be sensitive to aging processes. Each of the components of a model of working memory (central executive function, visuospatial sketchpad, phonlogical loop; Baddeley, 1986) will be tested with multiple converging measures. The second aim is to distinguish the patterns of change in performance on tests of memory and cognition that are associated with normal aging from changes associated with early dementia of the Alzheimer type. The third aim is to describe the natural history of dementia in adults with MR. Individual performance on tests of memory and cognition will be related to mental status and caregiver informant-based scales of adaptive behavior and dementia. Because the test battery spans a broad range of cognitive domains and difficulty, it will be possible to describe the course of decline from early onset through to advanced stages of dementia. By the end of the proposed study those tests that are most sensitive to early declines in functioning will have been identified and their utility as clinical instruments verified with longitudinal measures. By delineating the changes in specific memory and cognitive processes related to individual differences in normal and abnormal aging in adults with DS, this work will contribute to understanding vulnerability to age-related changes, in general. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODELING DYNAMIC RESOURCES TO SOLVE MOVEMENT PROBLEMS Principal Investigator & Institution: Ulrich, Beverly D. Kinesiology; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, MI 481091274 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The long-term goal of the work proposed here is to understand the production and change over time in patterns of motor behavior. The studies are informed by a dynamic systems perspective and expand the use of mathematical models that address coordination issues by focusing on the availability of dynamic resources from which humans select control strategies for solving movement problems. Recently such a model has been developed but limited in its validation to normal children and those with cerebral palsy (CP). This proposal addresses the generalizability of this modeling approach by focusing on a population with unique dynamic resources, Down syndrome (DS). It extends previous work by studying behavior across the lifespan in a population whose control problems are poorly understood. Focus is on walking because it emerges relatively early in life, is well practiced over time, complex, changes over the lifespan, is an important functional skill, yet has received limited directed attention by the scientific community. Specific aim #1 is to examine the capacity of the model to explain gait pattern differences in
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preadolescent children with DS and typically developing (TD) children as well as their ability to adapt to perturbations. Preadolescence is a time when performance on this task may be expected to be optimal. Comparison will be made between gait kinematics and the model's predicted dynamic gait strategies (i.e., relative stiffness and forcing functions. Specific aim #2 is to extend the application of this model across developmental levels, including new walkers and older walkers. At these levels optimality constraints may be quite different; they represent different levels of practice, as well as differences in the biomechanical and physiological constraints, within the same population. In particular, new walkers will be tested in a longitudinal study design in order to map the emergence of dynamic strategies within participants. Specific aim #3 is to concurrently validate the effectiveness of the model. This will include comparing the model's method for estimating stiffness and forcing to measures developed by other researchers, examining neuromuscular correlates of the model's estimates for stiffness and forcing, and determining if non-linear components in the model are required to minimize the error and maximize generalizability of the model. These studies have wide-ranging implications for a.) understanding the emergence of control strategies, b.) understanding general processes of change, and c.) impacting on clinical practice, especially physical and occupational therapy and orthopaedic medicine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODELING PHARMACOLOGICAL TREATMENTS IN THE TS65DN MOUSE Principal Investigator & Institution: Moran, Timothy H. Professor; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: The development of mouse models of Down Syndrome, with appropriate gene expression to mimic what takes place with a trisomy of human chromosome 21, provides test systems for potential therapeutic interventions aimed at improving cognitive performance. As detailed under Dr. Davisson's Project, the Ts65Dn mouse containing homologs to the majority of the genes on human chromosome 21. This segmental trisomy model has a number of distinct advantages over previous models, not the least of which is survival to adulthood. We and others have demonstrative a cognitive phenotype in the Ts65Dn mouse which has clear similarities to that seen in Down Syndrome. Ts65Dn mice demonstrate performance deficits in tests of learning and memory against a background of relatively intact motor and sensory abilities. Both acetylcholine and glutamate play important roles in learning and memory and are involved in neural organization during development. Alterations of cholinergic and glutamatergic activity in DS have been identified. The proposed experiments will 1) provide a more complete characterization of the development of cholinergic and glutamatergic systems in Ts65Dn mice. This characterization will provide a necessary background for proposed experiments aimed at, 2) assessing whether strategies aimed at blocking cholinergic degradation with the acetyl cholinesterase at, 2) assessing whether strategies aimed at blocking cholinergic degradation with the acetyl cholinesterase inhibitor donepezil or producing a development increase in cholinergic function with prenatal choline can improve performance in the Ts65Dn mouse, 3) assessing whether developmental treatment with piracetan alone, or piracetam combined with prenatal choline administration, improves performance in the Ts65Dn, and 4) assessing wheth4r developmental treatment with the neuroprotective agent acetyl-L-carnitine prevents cholinergic degeneration and results in improved cognitive
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performance in the Ts65Dn mouse. In these studies, we will assess performance in the Morris water maze and a cued and contextual conditioning paradigm. We will also monitor activity over the 24 hour cycle and in elevated plus maze paradigm. Behavioral assessments will be followed up by appropriate neurobiological analyses to determine whether the neurochemical systems impacted by these treatments respond similar in Ts65Dn and control mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MODULATION OF GLUTAMATE SYNAPSES IN NEONATAL CORTEX Principal Investigator & Institution: Friedlander, Michael J. Professor and Chair; Neurobiology; University of Alabama at Birmingham Uab Station Birmingham, AL 35294 Timing: Fiscal Year 2001; Project Start 14-JUN-2000; Project End 31-MAY-2005 Summary: Altered structural integrity of cortical synapses has been demonstrated in a variety of forms of mental retardation, including those attributable to chromosomal abnormalities (e.g., Down Syndrome, Fragile X, Angelman Syndrome, Praeder-Willi Syndrome, William's Syndrome), prenatal exposure to teratogens (e.g., ethanol) and severe neonatal seizures. Most of these structural defects are at synapses located on dendritic spines, sites of glutamatergic input, and they can occur in humans and animal models. The efficiency, distribution, and structure of these glutamatergic cortical synapses undergo substantial modulation by experience, neural activity, and other neurotransmitters such as serotonin during normal development. (Interference with normal glutamatergic synaptic transmission can lead to seizures, neurotoxicity, and development of abnormal cortical architecture). This program project is a multi-faceted inquiry into (1) the initial molecular assembly of the cortical glutamate synapse (Project I); (2) its capacity for transferring behaviorally relevant signals during development (Project II); and (3) its modulating during postnatal development by (i) two neighboring cell types-subcortical white matter neurons and astrocytes, (ii) the modulators, serotonin (5-HT) and nitric oxide, and (iii) the 5-HT and glutamate neurotransmitter transporters (Projects III, IV, and V). A Developmental Neurobiology Imaging Core (Core B) and an Administration/Project Development Core (Core A) Neurobiology Imaging Core (Core B) and an Administration/Project Development Core (Core A) will provide critical services and will promote synergy among projects. By learning the molecular components of these synapses, their functional properties in a physiological context, and the mechanisms of their modification by intrinsic gating pathway in the normal neonate, this project will provide a substantial new basis for understanding the sensitivity of developing glutamate synapses to the convergent processes that compromise synaptic structure and function in MR. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR BASIS FOR HYPOPLASTIC HEART SYNDROMES Principal Investigator & Institution: Olson, Eric N. Professor; Molecular Biology; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Congenital heart defects account for the largest number of birth defects in humans. Many heart defects can be attributed to abnormalities in specific steps in cardiac development, particularly in the formation and function of the ventricular chambers and in the neural crest-derived components of the heart. While the
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embryologic events involved in heart development have been carefully documented, little is known of the underlying mechanisms and molecules that control cardiac myogenesis and morphogenesis. The overall goal of this project is to elucidate the molecular mechanisms involved in specification and development of the ventricular chambers and the cardiac neural crest and to identify the genes responsible for defects in these cardiac compartments in three human chambers and the cardiac neural crest and to identify the genes responsible for defects in these cardiac compartments in three human syndromes associated with congenital heart disease: hypoplastic left heart syndrome, Down syndrome, and DiGeorge syndrome. Recently, the Olson lab found that two novel bHLH transcription factors, referred to as dHAND and eHAND, are expressed in specific subsets of ventricular precursor cells and in the cardiac neural crest and that mouse mutants lacking dHAND fail to form a right ventricle specification and cardiac neural crest and that mouse mutants lacking dHAND fail to form a right ventricle or cardiac neural crest derivatives. The discovery of these molecules provides a molecular entry point into the mechanisms for ventricular specification and cardiac neural crest development and establishes a conceptual framework for the overall SCOR. The SCOR contains four interwoven projects and three cores that encompass basic molecular strategies to understand cardiac development and clinical studies to identify the gens responsible for congenital heart diseases in which the ventricular and neural crest components of the heart are affected. The projects are as follows. 1) E. Olson will define the roles of the HAND family of cardiac basic helix-loop-helix (bHLH) transcription factors in normal and abnormal cardiac development. 2) D. Srivastava will define the downstream target genes regulated by dHAND in the developing heart, with particular attention to a recently discovered gene that is dHAND-dependent and is localized to the minimal chromosomal deletion in DiGeorge syndrome. 3) K. Chien will clone and characterize the gene responsible for hypoplastic left heart syndrome. 4) Korenberg will identify the gene(s) responsible for heart defects in Down syndrome. The possibility that one of the candidate genes, which encodes a novel cell adhesion molecule, called DS-CAM, is a transcriptional target for MEF2 will also be addressed. Each of these projects is interrelated through the creation of novel strains of mouse mutants in which key cardiogenic regulatory genes can be inactivated in a temporaland compartment-specific manner within the developing heart. These studies will provide an in-depth understanding of the basic molecular pathways that regulate heart development and the ways in which these pathways can be disrupted in congenital heart diseases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR DIVERSITY AND FUNCTION OF THE RECEPTOR DSCAM Principal Investigator & Institution: Schmucker, Dietmar; Dana-Farber Cancer Institute 44 Binney St Boston, MA 02115 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-APR-2007 Summary: (provided by applicant): We have recently identified the Drosophila receptor Dscam and shown that it is essential for the formation of proper connectivity in the fly nervous system. Dscam is a member of the immunoglobulin superfamily and is highly related to the human protein "Down syndrome cell adhesion molecule" (DSCAM). The Drosophila Dscam gene is extraordinarily complex and can generate some 38,000protein isoforms through alternative splicing. The overall goal of our studies is to test the hypothesis that alternative splice isoforms of the Dscam receptor constitute a molecular recognition code for synaptic specificity. We will use genetic and molecular
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approaches to functionally test the importance of neuronal receptor diversity. We propose that the extraordinary molecular diversity of Dscam provides a paradigmatic and genetically accessible case for systematically dissecting the mechanism by which neuronal receptors contribute to synaptic specificity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETIC EPIDEMIOLOGY OF THREE CARDIAC DEFECTS Principal Investigator & Institution: Lauer, Ronald M.; University of Iowa Iowa City, IA 52242 Timing: Fiscal Year 2001 Summary: (Adapted from the Applicant's Abstract) Congenital heart defects (CHDs) are thought to result from genetic and environmental factors that disturb cardiac embryogenesis. Because families with multiple members affected with atrial septal defects (ASDs) and atrioventricular canal defects (AVCDs) have been described, and the paramembranous ventricular septum is in part completed by the formation of the atrioventricular cushions, this project describes a genetic-epidemiologic study of ASDs, paramembranous ventricular septal defects (VSDs), and AVCDs. Three groups of subjects, each with surgically- or echocardiographically-confirmed diagnoses of ASDs, VSDs or AVCDs have been identified for study at the University of Iowa Hospitals and Clinics, and at Wolfson Children's Hospital in Jacksonville, Florida. A fourth group of older subjects with ASDs and their progeny will be studied at Iowa because of the reported high recurrence of heart disease in the offspring of subjects with ASDs. The strategy proposed calls upon the molecular genetic capacities available at the University of Iowa to carry out genome-wide searches for genetic loci involved in these defects. Several candidate regions have been identified for ASDs, VSDs and AVCDs. In addition, three well-recognized syndromes provide additional candidate regions - Down syndrome, Holt-Oram syndrome and 8p-syndrome. Parent-affected child trios will be genotyped for closely-spaced markers within these regions and linkage disequilibrium analysis will be used to narrow or exclude these candidate intervals. A genome-wide association study of the trios will employ a parsimonious technique in which DNA from cases with the same CHD phenotype will be pooled, and compared to the pooled DNA from their parents. Loci will be identified where the allele frequency distributions in the affected children and their parents are significantly different. When such loci are identified, a finer localization of the chromosomal area will be undertaken using a highdensity set of short tandem repeat polymorphic markers that spans each of the candidate intervals. This study has the potential to identify new candidate loci which are risk factors for the development of congenital heart defects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR MECHANISM OF THE MITOTIC CHECKPOINT Principal Investigator & Institution: Schuyler, Scott C. Molecular and Cellular Biology; Harvard University Holyoke Center 727 Cambridge, MA 02138 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2005 Summary: (provided by applicant): The broad long-term objective is to understand the process of chromosome segregation during eukaryotic cell division. Inaccurate chromosome segregation leads to genetic instability. Down syndrome is the most frequent genetic defect in infants and cancer will kill one American in four. Both are conditions caused by genetic instability and it is possible that lesions in the spindle
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checkpoint cause meiotic chromosome loss in Down syndrome and chromosome loss and gain in many tumors. The primary focus within the proposal is the study of the molecular mechanism by which chromosomes signal to stop cell cycle progression in response to mitotic spindle damage in budding yeast. The first specific aim is to identify the components of the complex that inhibit Cdc20p-APC activity in response to spindle damage. The second specific aim is to identify the kinetochore sensor necessary for activating the checkpoint signal complex. To achieve these ends, yeast molecular genetics coupled with classical protein biochemistry shall be employed. When used in combination these methods have been shown to be powerful tools for exploring the molecular roles of protein complexes. The hope is that understanding the molecular mechanism of the spindle checkpoint in budding yeast will help us to understand its role in human disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODEL OF RETARDATION IN DOWNS SYNDROME Principal Investigator & Institution: Gladzicki, Zygmunt; Henry M. Jackson Fdn for the Adv Mil/Med Rockville, MD 20852 Timing: Fiscal Year 2001; Project Start 01-APR-2001; Project End 28-FEB-2004 Summary: (Provided by applicant): Down syndrome (DS) or trisomy 21 (Ts21) is caused by the presence of three copies of chromosome 21, and is the most frequent genetic cause of mental retardation. The Ts65Dn trisomic mouse has recently been developed and is trisomic only for the segment of murine chromosome 16 that is homologous to the segment of human chromosome 21 thought to contribute to mental retardation and vulnerability to Alzheimer disease in DS. This mouse demonstrates abnormal behavior and is impaired in various learning paradigms. We demonstrated that long-term potentiation (LTP) and long- term depression (LTD) decrease and increase respectively in the CAl region of the Ts65Dn mouse of Ts65Dn mouse hippocampus. The objective of this proposal is to find mechanisms that cause the abnormal LTP and LTD. Three specific aims are proposed to test that abnormal LTP and LTD are due to changes in signal transduction pathways mediated by protein kinase A (PKA) and/or protein kinase C (PKC) that would cause posttranslational changes in voltage-dependent Na+, Ca2+ channels and NMDA-, AMPA-glutamate receptors and cause changes in synaptic activity in the hippocampus. Aim#1: Determine PKA pathway activity in Ts65Dn hippocampus in relation to LTP and LTD paradigm. Determine expression of phosphorylated CREB. Aim #2:PKC activity in Ts65Dn hippocampus in relation to LTP and LTD paradigm. Determine expression pattern of PKC isoforms. Aim #3:Determine the expression and posttranslational modification of voltage dependent Na+, Ca2+ channels and NMDA -, AMPA- glutamate receptors using nucleated patch-clamp recording technique and binding studies. The impact of PKC isoforms will be tested in cell lines that permanently over express Na+ channel, Ca2+ channels, NMDA and AMPA receptors. Signal transduction impairments in genetic model of DS will determine important targets for treatment of mental retardation. In addition the outcome of this research will include further understanding of the role of PKA and PKC and voltage-dependent channels and NMDA- and AMPA-receptors in the mechanisms that are behind LTP and LTD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOUSE MODELS OF DOWN SYNDROME Principal Investigator & Institution: Roper, Randall J. Physiology; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218
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Timing: Fiscal Year 2003; Project Start 01-MAR-2003 Summary: (provided by applicant): Trisomy 21 is the most frequent human aneuploidy compatible with survival. It occurs in 1 out of 700 live births causing a constellation of effects known as Down syndrome (DS). Significant efforts to establish the genetic control of the many phenotypes of DS have been made using mouse models. HSA21 is homologous with regions on mouse chromosome 10 (MMU10), MMU16, and MMU17. Extensive investigations have been done with Ts65Dn, a mouse model with segmental trisomy at dosage imbalance for about half of the genes on human chromosome 21 (HSA21). Using Cre-lox chromosome engineering, new models of DS will be made for MMU10 regions of conserved synteny with HSA21 including about 50 homologous genes. Quantitative phenotypes for trisomic (Ts2Rhr) and monosomic (Ms2Rhr) mice will be compared to clinical data for human trisomy and segmental monosomy 21. Additionally, Ts2Rhr/Ts65Dn compound transgenic mice will be used to assess the contribution of the MMU10 region in DS phenotypes. The importance of MMU10 will be verified using analysis of variance (ANOVA) and regression with comparisons between the different DS mouse models. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOUSE MODELS OF DOWN SYNDROME: PHENOTYPIC MAPPING Principal Investigator & Institution: Epstein, Charles J. Professor of Pediatrics; Pediatrics; University of California San Francisco 500 Parnassus Ave San Francisco, CA 94122 Timing: Fiscal Year 2001; Project Start 01-MAR-1995; Project End 30-NOV-2002 Summary: The overall objective of this research program is to discover the mechanisms by which the presence of an extra copy of human chromosome 21 produces the phenotype of Down syndrome (DS). The approach we are using is based on the premise that it will be possible to relate specific components of the trisomic phenotype to the increased expression of genes or sets of genes present on chromosome 21. Our work on this problem has led to the development of several animal models for DS including the full trisomy 16 (Ts16) mouse and, very recently, the new partial trisomy 16 mice, Ts1Cje and Ms1Ts65, which are trisomic from below Sod1 to Mx and from above App to above Sod1, respectively. In addition, we have studied Ts65Dn, another partial trisomy 16 mouse which is trisomic for the region App to Mx. The abnormalities of the Ts1Cje and Ts65Dn, which more faithfully reproduce the genetic imbalance that results in DS than does Ts16, are principally restricted to the nervous system and affect learning and behavior, although Ts65Dn is also male sterile. Ts65Dn, with the larger degree of imbalance, is more abnormal (in spatial learning) than is Ts108Cje. Furthermore, Ts65Dn mice display atrophy of basal forebrain cholinergic neurons (BFCN) which can be reversed by nerve growth factor, but Ts108Cje animals have normal BFCN. To determine the regions of chromosome that are responsible for the learning deficits and neuronal atrophy in the partial trisomy mouse for DS, we shall first compare in detail the behavioral differences among Ts1Cje, Ts65Dn, and Ms1Ts65. We shall then use an approach to phenotypic mapping that is subtractive in nature. It is based on the analysis of the changes in phenotype that result from decreases in the size of or the removal of specific loci from the region of trisomy. We shall analyze the effects of deleting either App or Sod1 on the phenotype of Ts65Dn. Then, starting with Ts65Dn and Ts108Cje, we shall generate two series of partial Ts16 mice with progressive radiation- induced deletions of chromosome 16. The resulting progeny will be assessed with regard to which phenotypic features of partial Ts16 disappear as extra copies of particular regions of the chromosome are no longer present. Regions so identified can then be further
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analyzed to identify candidate genes, and the true role of these genes in producing the phenotypic changes of partial trisomy 16 can be established by transgenic and homologous recombination techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTICENTER NETWORK OF MATERNAL-FETAL MEDICINE UNITS Principal Investigator & Institution: Carpenter, Marshall W. Associate Professor; Women and Infants Hospital-Rhode Island 101 Dudley St Providence, RI 02905 Timing: Fiscal Year 2001; Project Start 03-APR-2001; Project End 31-MAR-2006 Summary: (provided by applicant): WIH and the Department of Obstetrics and Gynecology at Brown University School of Medicine have the capability to participate actively as a new member of the Cooperative Multicenter Maternal-Fetal Medicine Units Network. WIH operates one of the nation?s larger obstetrical services. All obstetric care is supported by insurance in Rhode Island. Consequently, the State?s ethnic and racial diversity is reflected among both private and clinic patients. Providing care to 74 percent of the State s patients, WIH s demographic and clinical statistics wholly reflect those of Rhode Island. During fiscal year 1999, 9023 deliveries were performed at WIH, 2099 among WIH Clinic and Maternal-Fetal Medicine patients. Of the total WIH deliveries, 174 had ruptured membranes before 35 weeks, 556 delivered prior to 35 weeks, 207 had multi-fetal pregnancies, 179 had gestational or chronic diabetes, 794 had hypertensive disorders in pregnancy, 539 had asthma or other respiratory disease and 163 had cardiac or vascular disease. The academic faculty and private practice community have had a consistently collaborative relationship providing access to the entire obstetrical population for cohort studies. Consequently, WIH is particularly suited for performance of clinical trials. The Maternal-Fetal Medicine Division is composed of six board-certified and one active candidate for the Maternal-Fetal Medicine boards, all of whom will support Network research protocols. The Division also employs two research nurses and a sonographer, all presently supported by NICHD funding, and three additional clinical nurses, all with extensive experience in cohort research. The Division has successfully enlisted patients (53-100 percent enlistment rates) in complex tocolysis trials and exercise, and metabolic and hemodynamic cohort studies with retention rates of 79-93 percent. The Division has maintained strong clinical and investigational relationships with local and regional private obstetricians, reflected in the proportions of private patients in Divisional cohort studies of 54-80 percent. The Division is presently engaged in three multicenter cohort studies funded by NICHD. It was selected by the Network in April 2000 to participate in the Beneficial Effects of Antenatal Magnesium (BEAM) Study to increase patient enlistment in this protocol and is presently beginning to enroll subjects. The Division has been funded as one of five North American sites in an international study of the maternal and perinatal impact of maternal glucose intolerance, the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) Study. The Division is also a participant in the First and Second Trimester Evaluation of Risk (FASTER) Study examining combined biochemical and sonographic first trimester screening for Down syndrome. WIH and the Maternal-Fetal Medicine Division will enlist subjects for all Network protocols and actively participate in proposing, planning and executing Network studies. Local infrastructure available for participation in multicenter clinical trials at WIH include (1) a large patient volume and highly involved full-time and voluntary obstetrical faculty; (2) robust clinical patient, laboratory, anatomic pathology, and pharmacy databases; (3) a strong history of collaboration between Maternal-Fetal Medicine and Neonatology
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Divisions; (4) decades-old perinatal tissue samples and anatomic pathology; and (5) a strong Departmental commitment to outcomes research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MULTICENTER VITAMIN E TRIAL-PERSONS WITH DOWN SYNDROME Principal Investigator & Institution: Dalton, Arthur J.; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, NY 10314 Timing: Fiscal Year 2001; Project Start 30-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted from the application) There is evidence from a multicenter clinical trial that vitamin E slows the rate of clinical deterioration in individuals with moderately severe Alzheimer s disease (AD). The AD Cooperative Study (ADCS) is now mounting a large study to test the effects of vitamin E in persons at the earliest stage of cognitive deterioration. Older individuals with Down syndrome (DS) are at very high risk for AD. Most individuals with DS develop functional decline and show neuropathological evidence of AD by the sixth decade. The applicants propose an international multicenter randomized double-blind study to determine whether vitamin E supplementation will slow the rate of cognitive/functional decline in individuals with DS. Subjects with DS who are at least 50 years of age will be randomized into two treatment groups: vitamin E 2000 IU plus a multivitamin per day or placebo plus multivitamin. The multivitamin contains vitamin E 15 IU. The treatment period will be three years with evaluation visits every six months. The primary outcome measure will be a three year change score on a cognitive/functional measure that was derived for this purpose from the DYSPRAXIA Scale for Adults with Down Syndrome. Secondary outcome measures will include additional cognitive tests as well as informant-based measures of function and behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NATURE AND DEVELOPMENT OF SPATIAL COGNITION IN AUTISM Principal Investigator & Institution: Ogline, Jamie S. Psychology; University of Denver Box 101562 Denver, CO 80208 Timing: Fiscal Year 2001; Project Start 01-JUN-2001 Summary: The overall goal of the proposed research is to examine the nature and development of spatial cognition in individuals with autism. Although previous research suggests that spatial cognition may be a strength in those with autism, research findings in this area are inconsistent and need further examination. For instance, central coherence theory claims that those with autism have difficulty attending to the gestalt and will focus more on the local parts of a spatial configuration. This theory is inconsistent with the possibility that individuals with autism may have a strength in the spatial domain because many spatial tasks require attention to both the global and local parts of configurations. Another inconsistency is evident between previous findings of executive deficits in autism and the findings that individuals with autism are not impaired on spatial tasks that may require executive processing, such as the WISC block design. The proposed study will attempt to resolve these inconsistencies and add to knowledge about spatial cognition in autism by testing low-functioning children with autism as compared to Down syndrome and normally developing mental age matched control groups using measures of spatial working memory, global/local processing, and a spatial task previously not examined in this population. Broadening knowledge about
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spatial cognition in this disorder will allow for a better understanding of development in this disorder and any potential strengths that may exist. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROBEHAVIORAL STUDIES OF LANGUAGE IMPAIRMENT Principal Investigator & Institution: Wulfeck, Beverly; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 16-SEP-1985; Project End 31-JUL-2006 Summary: A growing body of research is challenging the notion of specific language impairment. Our investigations of language-impaired children (LI) reveal limitations in language, but neurologic abnormalities and deficits in other cognitive domains have also been noted. Further insights require study of non-verbal cognition as well as language, and the neural substrates that subserve them. Because LI can extend into adulthood, we will include adolescents with LI in our studiers. The major aims of this project are: 1. Study basic language processing abilities across a wider age range (7- 16) and examine higher order language to determine how early LI impacts on later language use and literacy. 2. Test for associations and dissociations and differentiate knowledge from processing deficits. 3. Study attention, spatial localization, laterality, visual memory and mental rotation abilities and examine for selective sparing and/or impairment across non-verbal cognitive domains. 4. Test for patterns of association and dissociation between language and cognition. 5. Conduct fMRI and ERP studies of language using paradigms tightly yoked to behavioral measures to examine languagebrain mappings in LI children. 6. Conduct fMRI and ERP studies of spatial cognition and attention using paradigms tightly yoked to behavioral measures to examine for patterns of sparing and impairment in non-verbal cognition. 7. Conduct longitudinal studies of LI to examine developmental trajectories for evidence of differential catching up or continued impairment across language and cognitive domains. 8. Compare LI results to results from children with different etiologies including early focal brain injury (FL), Williams or Down Syndrome, and FL Variants (i.e. bilateral or late onset brain lesions) to further characterize the contrasting behavioral profiles noted in the last funding period and determine whether these are associated with alternative forms of brain organization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEUROGENESIS IN DISORDERS OF BRAIN DEVELOPMENT Principal Investigator & Institution: Krueger, Bruce K. Physiology; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001; Project Start 14-JUL-2000; Project End 30-APR-2004 Summary: (adapted from applicant's abstract): The cause of mental retardation in Down syndrome (DS) is not understood but is thought to result, at least in part, from defective brain development during the embryonic period when neurons of the cerebral cortex are being generated. The trisomy 16 (Ts16) mouse shares a common genetic defect with DS and may be useful for studying the mechanisms underlying abnormal embryonic development of the cerebral cortex. Prenatal generation of postmitotic neurons in the Ts16 mouse cortex is delayed and subplate neurons are born concurrently with cortical plate neurons rather than preceding them as in the normal cortex. These abnormalities in the timing of Ts16 neurogenesis may lead to defective connectivity in the mature brain; similar defects during the prenatal development of the human brain may contribute to mental retardation in DS. Proliferation of neuroprogenitor cells
62 Down Syndrome
(neuroblasts) and the decision of daughter cells to leave the cell cycle, which ultimately control the timing of neurogenesis, are regulated by neurotransmitters and growth factors such as glutamate and brain derived neurotrophic factor (BDNF). Ts16 neuroblasts fail to respond to glutamate and BDNF, raising the possibility that this signaling defect may underlie delayed neurogenesis in Ts16. The molecular basis for defects in the regulation of Ts16 neurogenesis will be studied in a) dissociated cell cultures of neuroblasts and b) organotypic slices from Ts16 and littermate euploid cortex. Both of these preparations enable not only the direct application of putative regulators of neurogenesis and of inhibitors of signaling pathways, but also direct measurement of proliferation, cell death and intracellular levels of Ca2+, a key modulator of proliferation, neuronal differentiation and migration. Experiments in organotypic slices will enable these processes to be analyzed in a structurally intact cortex and will allow the behavior of anatomically-distinct populations of neuroblasts and postmitotic neurons to be distinguished. The overall goals of this research project are to identify the signaling defects that lead to abnormal neurogenesis in the Ts16 mouse cerebral cortex and, at the same time, to determine the molecular signaling mechanisms underlying the control of neurogenesis in the normal brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPSYCHOLOGICAL BASIS OF THE BROAD AUTISM PHENOTYPE Principal Investigator & Institution: Piven, Joseph; Professor; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): For over 15 years our research team and others have taken Kanner?s original observations about personality features characteristic of some parents of autistic individuals and developed definitions of, and standardized measures for, a broader autism phenotype. The broad autism phenotype (BAP) is thought to represent the phenotypic expression of the genetic liability to autism in non-autistic relatives of autistic probands, and is defined by characteristics that are milder but qualitatively similar to the defining features of autism. This work has potential importance for 1) teasing apart the gene-behavior relationships in autism, 2) understanding brain-behavior relationships in autism and, 3) providing additional qualitative and quantitative information on the range and nature of the phenotypic expression of autism genes, which may augment our ability to find those genes. While autism and the BAP are defined by particular behavioral characteristics, they are clinically and etiologically heterogeneous, and are the end result of a range of underlying neuropsychological, neural and genetic mechanisms. In this project we propose to examine the relatives of autistic and Down syndrome probands on selected neuropsychological measures of social cognition, central coherence and executive function, three principal cognitive frameworks proposed as theories to explain the neuropsychological basis of autism. These neuropsychological characteristics will be examined in relationship to our clinically-based measures of the BAP, in order to both elucidate the neuropsychological basis of the BAP and to provide efficient, valid and reliable measures for future studies of the BAP. Autism and OS relatives will be compared in these three neuropsychological domains, to a unique sample of individuals with focal brain lesions in the amygdala, orbital-frontal cortex and right somatosensory cortex, drawn from a brain injury registry at the University of Iowa, to provide insights into the neural basis of the behavioral and neuropsychological characteristics of autism and the BAP. Finally, patterns of co-occurrence of these characteristics will be examined
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in individuals and families. This study will complement ongoing studies of the same neuropsychological characteristics in autistic probands. This project brings together a unique group of experienced researchers with complementary expertise in familygenetic (Piven) and neuropsychological studies of autism (Happe), and in the neural basis of social cognition (Adolphs), to study the neuropsychological basis of the broad autism phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROPSYCHOLOGY OF DOWN SYNDROME Principal Investigator & Institution: Pennington, Bruce F.; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001 Summary: In contrast to several other mental retardation syndromes, the neuropsychology of Down Syndrome is relatively unexplored. The proposed research will fills gap in existing knowledge by testing the functional status of three neural systems particularly at risk in DS: the prefrontal cortex, hippocampus, and cerebellum. We will examine these three neuropsychological domains in a cross-sectional study of two age cohorts of individuals with DS (n=36 each) compared to two control groups, 1) younger normally developing children matched on MA, and 2) CA and MA matched children with non-DS mental retardation. Our component will provide a target phenotype for our colleagues working with mouse models, which will help them isolate the specific genetic determinants of the neural bases of this form of mental retardation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NGF SIGNALING NEURODEGENERATION
IN
MODELS
OF
AGE
RELATED
Principal Investigator & Institution: Mobley, William C. Professor, and Chairman; Neurology & Neurological Scis; Stanford University Stanford, CA 94305 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 31-AUG-2003 Summary: The broad long-term goal is to elucidate the mechanisms responsible for the dysfunction and loss of neurons in degenerative neurological disorders. In Alzheimer's disease (AD) and Down syndrome (DS), age- related degeneration of basal forebrain cholinergic neurons (BFCNs) contributes significantly to dementia. Defining the molecular events leading to BFCN degeneration would significantly advance our understanding of pathogenesis. In studies on the Ts65Dn mouse, a genetic model for DS, we documented age-related degeneration of BFCNs. Nerve growth factor (NGF) is essential to the function of normal BFCNs and recent findings suggest that failed NGF signaling contributes to their degeneration of Ts65Dn. We will test the hypothesis: that a failure in NGF signaling is responsible for the degeneration (i.e. progressive dysfunction) of BFCNs in the Ts65Dn mouse. The proposed Specific Aims are: 1) To characterize the functional status of BFCNs and document age-related dysfunction of these neurons in Ts65Dn mice. Using unbiased stereology, biochemical and behavioral studies we will document the time of onset of BFCN dysfunction in Ts65Dn mice. 2) To determine if NGF signaling is defective in BFCNs in Ts65Dn and, if so, to determine whether the abnormality predate degeneration of BFCNs. Abnormal NGF retrograde transport will be used to document the existence of a signaling defect and biochemical studies will define its nature and time of onset. 3) To determine whether disrupting NGF signaling reproduces the cholinergic abnormalities seen in Ts65Dn. If the NGF signaling defect demonstrated in Aim 2 is sufficient to produce the degeneration of
64 Down Syndrome
BFCNs in Ts65Dn, animals defective for NGF signaling should show the same degenerative events. We will examine mice treated with NGF antibodies to sequester endogenous NGF, mice in which one copy of the NGF gene has been disrupted, and mice in which both copies of the gene for the NGF TrkA receptor has been knocked-out. 4) To define NGF actions on degenerating BFCNs in Ts65Dn. Current data suggest that NGF may be capable of reversing other aspects of BFCN degeneration. In this Aim, we will determine whether NGF reverses the degenerative phenotypes defined in Aim 1. 5) To determine whether BFCN degeneration is found in other genetic models of Ds and AD and, if so, whether failed NGF signaling is present. We will examine BFCNs in several models of AD. If BFCN atrophy is detected, we will determine whether there is an abnormality of NGF signaling. We will also examine Ts65Dn animals expressing either human Apo E3 or E4 to determine whether, as expected, BFCN degeneration is worse in ApoE4 expressing mice. Evidence that abnormal NGF signaling is responsible for BFCN degeneration in models of AD and DS will give important new insights into pathogenesis and may suggest novel approaches to prevent or reverse dementia in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NONDISJUNCTION AND PHENOTYPES IN DOWN SYNDROME Principal Investigator & Institution: Hassold, Terry J. Professor of Genetics; Johns Hopkins University 3400 N Charles St Baltimore, MD 21218 Timing: Fiscal Year 2001 Summary: Trisomy 21, the chromosome abnormality associated with over 95% of Down syndrome (DS), is the most important genetic cause of mental retardation, with an estimated incidence of 1/600 livebirths. Despite its high rate of occurrence and obvious clinical importance, we still know surprisingly little about the mechanism of origin of trisomy 21 or about factors which may predispose to non-disjunction of chromosome 21. In the proposed studies, we intend to combine cytogenetic, molecular and epidemiological approaches to address these questions. In one set of investigations we will focus on the genesis of trisomy 21, conducting studies to determine the effect of aberrant recombination and paternal non-disjunction, with particular emphasis on examining the association between maternal age and trisomy 21. In companion studies, we will investigates the hypothesis that specific environmental exposures may influence the frequency of trisomy 21, and confirm or refute preliminary observations that two such factors-smoking and oral contraceptive use-are risk factors for trisomy 21. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OBSESSIONS & COMPULSIONS: PRADER-WILLI & OTHER SYNDROMES Principal Investigator & Institution: Dykens, Elisabeth M. Associate Professor; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, CA 90024 Timing: Fiscal Year 2001; Project Start 01-AUG-1997; Project End 31-MAR-2003 Summary: (adapted from the applicant's abstract): Prader-Willi syndrome (PWS) has long been characterized by hyperphagia, food obsessions, and increased risks of obesity in affected individuals. Although less well-described, many people with PWS show obsessions and compulsions not related to food, as well as significant behavioral dysfunction. The proposed study will examine these obsessions, compulsions, and other maladaptive features, filling a long-standing behavioral research void in this complex
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developmental disorder. To this aim, the investigators propose to identify the onset, course, and phenomenology of obsessive-compulsive symptoms in PWS, and how these relate to children with obsessive-compulsive disorder (OCD). PWS is hypothesized to represent a specific clinical subtype of OCD, opening up possible roles for genomic imprinting or the PWS Critical Region in delineating these subtypes. It is hypothesized that compulsivity in PWS has an unusually early-onset, and that salient features of the PWS cognitive-behavioral phenotype may provide new clues into how compulsivity is expressed in young children. Early-onset compulsivity is also likely associated with aspects of hyperphagia and of normative development. The second aim is to identify possible mechanisms in PWS that mediate the expression of compulsivity. The proposed study hypothesizes that whole-blood serotonin will mediate symptom expression, and that subtle differences in symptoms may be seen across PWS subjects with paternallyderived deletions at 15q11-q13 versus those with maternal uniparental disomy of chromosome 15. Third, the investigators aim to determine the distinctiveness of compulsivity in PWS relative to children with Williams syndrome (WS), and Down syndrome (DS). WS is a particularly powerful contrast group as it is characterized by increased anxiety and obsessional thinking. The three aims will be addressed in two ways: 1) a longitudinal study of 60 children with PWS, WS, and DS aged 2 to 7 years who are tested twice, two years apart; and 2) a cross-sectional study of 35 children with PWS aged 10-14 years who are compared to subjects with WS, DS, and appropriately matched children with OCD. Findings will shed new light on treatment, on certain subtypes of OCD, and on the range and correlates of PWS' complex behavioral phenotype. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHOLOGICAL SIGNIFICANCE OF ENDOCYTIC PATHWAY Principal Investigator & Institution: Cataldo, Anne M.; Nathan S. Kline Institute for Psych Res Psychiatric Research Orangeburg, NY 10962 Timing: Fiscal Year 2001 Summary: The endocytic pathway )EP) is central to the function of amyloid precursor protein (APP), Abeta, apolipoprotein E and other molecules etiologically linked to Alzheimer's disease (AD) pathogenesis. Recently, we identified abnormalities of early endosomes (EE), implying strong EP activation, in control and hippocampal neurons before beta-amyloid deposition in sporadic AD (SAD) and Down Syndrome (DS). The overall objective of this project is to define the consequences of EP abnormalities for Abeta production, Abeta clearance, and cell survival in SAD and the influence of APOE genotype and vascular risk factors on these interrelationships. In well-characterized AD brains at the APOE epsilon allele accentuates the onset and magnitude of EE abnormalities (Aim 1). Based on preliminary data, we will investigate the localization and increased context of Abeta in EE from SAD and early DS brain using ICC and confocal microscopy on tissues and on purified EE fractions using immunoblot assays (Aim 1). Based on preliminary data, we will investigate the localization and increased content of Abeta in EE from SAD and early DS brain using ICC and confocal microscopy on tissues and on purified EE fractions using immunoblot assays (Aim 1) and immunoEM. Changes in the protease composition of EE will also be analyzed based on our earlier findings of increased lysosomal hydrolase expression and trafficking to EE in AD. In Aim 2, we will model the abnormalities seen in SAD and DS by appropriate genetic manipulations that upregulate endocytosis and direct hydrolyases preferentially to EE in transfected cells and transgenic mice to test predicted effects of these SAD mechanisms on Abeta biology and cell survival. In Aim 3, the evolution of these EPO
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abnormalities will be investigated in mice trisomic for a segment of the human homolog of chromosome 21 where we have seen EP disturbances, including Abeta accumulation in EE, which are similar to those in mice expressing human APOE alleles. In aim 4, neuron-vascular interrelationships suggested by the presence of EP and lysosomal system activation in cerebrovascular endothelia will be investigated by characterizing these abnormalities in SAD, inherited cerebral amyloid angiopathy (CAA), and animal and cultured human endothelial cell models of CAA and ischemia. This project will clarify the hypothesized role of EP abnormalities, the earliest known cellular response in SAD, in accelerating amyloidogenesis as well as generate novel models of SAD-relevant pathology and identify new targets for possible therapeutic intervention at stages of disease well before clinical onset. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PERCEPTUAL AND MOTOR BEHAVIOR IN DOWN SYNDROME Principal Investigator & Institution: Elliott, Digby; Mc Master University Hamilton L8s 4L8, Canada Hamilton, Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 30-JUN-2002 Summary: As well as general intellectual difficulties, children and adults with Down syndrome exhibit a number of specific information processing problems, some of which are associated with an atypical pattern of brain organization in these individuals. For example, compared to other children and adults of a similar mental age, persons with Down syndrome have difficulty performing sequential limb and oral movements on the basis of verbal direction. The position taken in this research program is that this problem is due to the functional dissociation of the cerebral areas responsible for speech perception and those responsible for movement organization. This research program has four interrelated objectives. The first is to develop a neurobehavioral index of cerebral organization in persons with Down syndrome that will reliably predict individual differences in verbal-motor performance. The protocol, which involves performing rapid limb and oral movements following the dichotic presentation of verbal stimuli, will be validated using the latest in brain-imaging technology. The second objective is to use the brain- imaging technology to extend the understanding of cerebral organization in persons with Down syndrome to visual-spatial function, visuallanguage function and visual and auditory attentional processes. The third objective involves studies to extend research on sequential oral and limb movements to movements involving the coordination of effectors with each other and with information from the environment. The final objective involves experiments conducted to determine if verbal-motor performance findings involving children and adults with Down syndrome generalize to perceptual-motor skill acquisition. Of interest is whether or not the neurobehavioral and neurophysiological indices of cerebral organization associated with the first two research objectives predict skill acquisition in different instructional and rehabilitation contexts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROBING CELLULAR FUNCTIONS OF THE MINIBRAIN KINASE Principal Investigator & Institution: Hwang, Yu-Wen; Institute for Basic Res in Dev Disabil Developmental Disabilities New York, NY 10314 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: The Minibrain (Mnb) gene is mapped to the Down syndrome critical region of human chromosome 21. Evidence suggests that an elevated Mnb gene dosage, as in
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trisomy 21, contributes to Down syndrome phenotypes. The Mnb encodes a dual specificity protein kinase whose cellular function has yet to be determined. Our preliminary results suggest that MnB kinase is involved in controlling the activity of dynamin-1, while its enzymatic activity is in turn regulated by rabaptin-5 and a novel cysteine-rich protein. Since both dynamin-1 and rabaptin-5 are part of endocytosis machinery, it also suggests that the Mnb kinase must play an essential role in regulating endocytic membrane trafficking. We plan to pursue the following specific aims in this study: 1. To establish the Mnb kinase as the enzyme responsible for regulating dynamin1 physiological activity through phosphorylation. 2. To determine the mechanisms of regulating the enzymatic activity of Mnb kinase by rabaptin-5 and the cysteine-rich protein. 3. To characterize the biochemical properties of dynamin-12 phosphorylated by Mnb kinase. 4. To study the effects of Mnb kinase over-expression on endocytic membrane trafficking. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROCESSING PREGNANCIES
OF
HCG
IN
NORMAL
AND
ABNORMAL
Principal Investigator & Institution: Cole, Laurence A. Obstetrics and Gynecology; University of New Mexico Albuquerque Controller's Office Albuquerque, NM 87131 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: Preliminary studies in our laboratory are consistent with a relationship between hyperglycosylation (additional antennae and fucose residues on N-linked oligosaccharides) and nicking or cleavage of hCG. Other preliminary studies indicate the structural instability and diminished biological activity of hyperglycosylated and of nicked hCG molecules, and how they may be the source of free beta-subunit in the circulation and beta-core fragment in urine samples. Papers have been published showing raised hCG levels, and raised proportions of free beta-subunit and beta-core fragment levels in serum or urine samples from patients with trophoblast disease, hyperemesis gravidarum, or Down syndrome pregnancies. It is our hypothesis these raised levels arise from the hyperglycosylation of hCG, through pathways involving nicking, ineffectual autocrine control of hCG production, and dissociation to nicked free beta-subunit, and degradation to beta-core fragment. Other pathways raise levels of hCG and lower the proportions of hyperglycosylated hCG in patients with preeclampsia. Four sets of experiments are proposed to test this hypothesis and investigate the clinical ramification of the observations in normal and abnormal pregnancies. Studies are proposed to confirm and compare the levels of hCG, free betasubunit and beta-core fragment in 1140 sets of parallel serum and urine samples from normal and abnormal pregnancies (Aim 1A); and to use the parallel serum and urine samples to investigate the clinical use of two new immunoassays that specifically measure hyperglycosylated hCG and nicked hCG, and their potential uses in screening for Down syndrome and preeclampsia (Aim 1B). Basic science studies are proposed to purify hCG from normal first, second and third trimester pregnancy urine samples, and preeclampsia, hyperemesis trophoblast disease and Down syndrome pregnancy urine samples (3 each) and compare the extents and sites of nicking, and the type, amounts and locations of hyperglycosylated N-linked oligosaccharides (Aim 2). Further studies are planned to investigate the hyperglycosylation- nicking relationship by comparing normal and hyperglycosylated hCG as substrates for nicking enzymes (Aim 3); and to examine the biological activities of the 21 purified normal and abnormal pregnancy molecules, and to determine their ability abilities to feedback through to the placenta and control hCG synthesis (Aim 4).
68 Down Syndrome
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF ARGININE-NITRIC OXIDE CYCLE IN BRAIN Principal Investigator & Institution: Jackson, Marian J.; University of Maryland Balt Prof School Baltimore, MD 21201 Timing: Fiscal Year 2001 Summary: Regulated synthesis of nitric oxide (NO) from arginine plays a key role in normal neural development, signalling, and response of the brain to trauma and infections. However, excessive NO production (as may result from trauma or inflammatory stress) can cause cell injury and/or death resulting in impaired brain function. Our data show that arginine synthesis is coordinately regulated with nitric oxide synthase (iNOS) induction in bacterial lipopolysaccharide-or S100B-treated astrocytes. Augmentation of argininosuccinate synthetase (AS), which catalyzes the ratelimiting step in arginine synthases, facilitates recycling of citrulline to support ongoing NO production under conditions of arginine depletion. We hypothesize that an arginine-nitric oxide cycle functions in neural tissue to insure that arginine availability does not limit NO synthesis. Several lines of evidence suggest that altered brain metabolism in response to these mediators may play a role in the development of mental retardation. Epidemiological studies have shown an association between intrauterine or perinatal infectious and development of mental retardation in some nongenetic causes of mental retardation. For patients with inborn efforts of metabolism, hyperammonemia during intercurrent infections is though to be causative in generating neural damage. S100B (which has been shown to induce neurotoxic levels of NO) maps to the Down syndrome region of chromosome 21. Its expression is elevated throughout development in Down Syndrome patients. In the proposed studies we will perturb brain cells with lipopolysaccharide (LPS, to mimic infection) or with S100B and we will determine the mechanisms which influence the capacity of brain cells to synthesize arginine under steady-state and stress conditions. We will evaluate the possible compartmentation of arginine and nitric oxide metabolism in cerebral cortex and cerebellum, two regions of the brain which differ in their content of nitrergic neurons. In addition, we will determine the effects of LPS-stimulated inflammatory stress on the flux of nitrogen metabolism through arginine versus glutamine synthesis. The molecular mechanism(s) by which LPS and S100B coordinately up-regulate argininosuccinate synthetase and inducible nitric oxide synthase in astrocytes will be determined using biochemical and molecular genetic techniques. We will examine AS enzyme kinetics, synthesis and gene expression. These studies will provide insight into alterations of brain nitrogen metabolism which occur in response to infection or trauma and will lay the groundwork for designing therapeutic strategies to limit their neurological consequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RESEARCH ON COGNITION AND BEHAVIOR IN DOWN SYNDROME Principal Investigator & Institution: Nadel, Lynn; Professor; National Down Syndrome Society 666 Broadway, 8Th Fl New York, NY 10012 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2004 Summary: (provided by applicant): The Research Conference on Cognition and Behavior in Down Syndrome will be held in the United States under the auspices of the National Down Syndrome Society (New York, NY) and the Down Syndrome Research
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Foundation (Vancouver, BC). The conference will be convened under the direction of the NDSS and DSRF Science Advisory Boards, in collaboration with a conference organizing committee. The meeting will review and document the current status of research on cognitive function and behavior in Down syndrome, including an overview of current neuroscientific research and the use of mouse models. It will also review current knowledge about applying research findings to early stimulation and education programs that aim to optimize the functioning and status of individuals with Down syndrome. Finally, it will explore the directions that future research on this genetic condition should take. Plenary sessions will focus on the link between Down syndromespecific and non-Down syndrome-specific research, the state of the art in research on cognition and behavior, motor skill development, functional MRI imaging, and dementia and memory across the lifespan. Paper presentations and working groups will address the current status of research in the areas of imaging, sleep and memory, mental health, mouse models, speech and language and positive behavioral support. Research priorities and potential areas of collaboration in these key areas will be determined by working groups and shared with the entire audience. There will also be a poster session for scientists to present work on specific related topics, as well as on more broad-based Down syndrome research. The conference will provide several opportunities for participants to interact with colleagues, synthesize and share knowledge, develop new collaborations and generate ideas about practical applications. The ultimate goal is for this conference to facilitate progress in research and practice on cognition and behavior in Down syndrome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RETT SYNDROME: DETERMINANTS OF OUTCOME AND BURDEN Principal Investigator & Institution: Leonard, Helen M.; University of Western Australia Crawley, Wa, 6009 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This population-based study will follow the current cohort of live (n=225) cases with Rett syndrome in Australia for a further five years. New cases ascertained during the study period will also be included. It will describe the natural history of Rett syndrome and assess its impact on resource utilization and the economic and social burden on families and community in comparison with Down syndrome and a normal comparison group. Baseline data on communication, mobility, symptoms and classification have been gathered on the cohort since 1993. In 2000 data were collected on functional ability in daily living, behavior, hand function, medical conditions, and use of health and education services. Mutation data, collected on 80 percent of cases will be continued. A questionnaire has been developed, piloted and will be used to collect data on function, health and well-being of the Rett syndrome subjects and family in 2002, 2004 and 2006. Data will be gathered for the Down syndrome comparison group in 2003. Participants will respond via paper-based or through secure on-line formats. Optical scanning or on-line data capture will be used for data entry. In 2003 and 2005 clinical assessments or clinical file review will provide EEG, ECG, blood parameters, bone densitometry and autonomic nervous system data. A video protocol developed in 2001 to record functional ability will be extended to include gross motor and oral motor function, hand apraxia, gait assessment and language function. Serial videos collected in 2003 and again in 2005 will enable us to monitor changes over time and the effect of therapy or surgery. Yearly telephone interviews to families will record anthropometric data, current medication usage and update previously collected family tree data. Every two years a validated questionnaire to identify epilepsy type will be
70 Down Syndrome
included. Resource data to determine the direct, indirect and opportunity costs associated with Rett syndrome will be compared with a normal and Down syndrome comparison group. Data analysis will use multiple regression models to examine effects of different variables on child and family level outcomes and discriminant analysis, recursive partitioning and machine learning to identify genotype/phenotype associations at the individual child level. Feedback to families on study progress will be given through the study Web site. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ROLE FOR FIBROBLAST GROWTH FACTOR IN ALZHEIMER'S DISEASE Principal Investigator & Institution: Barnea, Ayalla; University of Texas Sw Med Ctr/Dallas Dallas, TX 753909105 Timing: Fiscal Year 2001 Summary: Our long-term objective is to gain insight into the cellular and molecular mechanisms underlying the initiation and progression of neuronal death in the brain, particularly in brains of Alzheimer patients. The goal of this pilot study is to establish a culture study of fetal brain cells derived from "normal" human abortuses and from Down Syndrome (DS). These cultures will serve as models for the study of processes leading to neuronal death in Alzheimer disease. The rational for choosing the DS brain is based on the consistent findings that DS patients develop Alzheimer neuropathology at a much earlier age than "normal" aging people and on the hypothesis that processes leading to Alzheimer neuropathology at a much earlier age than "normal" aging people and on the hypothesis that processes leading to Alzheimer neuropathology are operative at an earlier age, possibly already even in the fetus. S.A.1. Establish a human model system for the study of the regulation of neuronal survival Aggregate cultures comprised of neurons and glial cells will be established from dissociated brain cells obtained from the cortex of "normal" human abortuses and of DS brains, using our previous experience with this culture system derived from rat fetal brains as a guideline. Two population of peptidergic neurons, neuropeptide Y (NPY) and somatostain (SRIF), will serve as model neurons. The morphological and functional differentiation of these neurons and the topographical arrangement of the cells will be defined. S.A.2. Test our "ping pong" hypothesis of basic fibroblast growth factor (bFGF) - Beta-amyloid interactions. Neurite sprouting has been implicated in the early stages of senile plaque formation in Alzheimer disease. Our working "ping pong" hypothesis is that bFGF stimulates expression of the gene encoding Beta-amyloid precursor protein (APP), a product(s) of which, in turn, stimulates more bFGF production. Thus, each round of bFGF - Beta-amyloid interaction results in greater extracellular levels of agents capable of promoting neurite sprouting, of which Beta-amyloid may be a substantial component. We will initiate this study by assessing the effect of bFGF on neurite sprouting and survival of NPY/SRIF neurons in our human model systems. These results will serve as the basis for a full-scale research proposal to elucidate the cellular and intracellular mechanisms underlying bFGF - Beta-amyloid interactions in processes leading to neuronal death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ROLE NEUROPATHOLOGY
OF
ETS-2
AND
SOD-1
IN
DOWN
SYNDROME
Principal Investigator & Institution: Busciglio, Jorge A. Assistant Professor; Pharmacology; University of Connecticut Sch of Med/Dnt Bb20, Mc 2806 Farmington, CT 060302806 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2004 Summary: Down's syndrome (DS) or trisomy 21 is the most frequent genetic cause of mental retardation. It occurs in about 1 in 800 to 1 in 1000 live births. Mental retardation and development of Alzheimer's disease (AD) by middle age are hallmarks of DS neuropathology. Previous studies demonstrated that DS neurons in culture exhibit elevated intracellular free radicals and lipid peroxidation leading to increased neuronal death. This increase in oxidative stress and neurodegeneration may contribute to mental retardation and the development of AD in DS patient. The goal of our research is to characterize the molecular mechanisms involved in neuronal oxidative stress and degeneration in DS. This project will study the role of Ets-2 and Cu/Zn superoxide dismutase (SOD-1) over- expression in DS neurodegeneration. The following hypotheses will be tested: 1. Over-expression of the transcription factor Ets-2 in DS neurons compromises neuronal viability by altering the expression of genes that control neuronal survival and death. More specifically, the possibility that Ets-2 down-regulates Bcl-2 and up-regulates Bax and p53 protein levels will be tested. 2. Increased activity of Cu/Zn superoxide dismutase (SOD- 1) may contribute to oxidative stress and DS neuronal degeneration. The research will focus on: 1) the functional analysis of Ets-2 and SOD-1 in DS and Ets-2 transgenic neurons in culture; and 2) the association of Ets- 2 and SOD-1 with neurodegenerative changes in the brains of DS and AD patients and Ets-2 transgenic mice. The specific aims are: 1: to determine the role of Ets-2 over-expression in DS neuronal degeneration in culture and in the brains of DS and AD patients. 2: To characterize the role of Ets-2 during normal neuronal development. 3: To determine the role of SOD-1 in DS neuronal degeneration. These experiments will provide valuable information towards understanding the molecular basis of neuronal dysfunction and death in DS and AD. In addition, the results of this investigation may identify new molecular targets for the design of neuroprotective therapies for the treatment of mental retardation and the prevention of AD in DS patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SISTER CHROMATID LINKAGE AND SEPARATION Principal Investigator & Institution: Murray, Andrew W. Professor; Molecular and Cellular Biology; Harvard University Holyoke Center 727 Cambridge, MA 02138 Timing: Fiscal Year 2001; Project Start 01-MAY-1997; Project End 31-MAY-2005 Summary: (APPLICANT'S ABSTRACT): Accurate chromosome segregation is essential for the faithful transmission of genetic information. The linkage between sister chromatids directs them to attach to opposite poles of the mitotic spindle, and the prompt dissolution of this linkage allows chromosomes to segregate to the poles at anaphase. Mitotic chromosome movements depend on kinetochores, which also act as signaling centers to delay anaphase until all the chromosomes have been correctly aligned on the spindle. This proposal describes experiments to investigate kinetochore assembly and function, the nature of the linkage between sister chromatids, and the mechanisms that regulate this linkage during the eukaryotic cell cycle. Frog egg extracts will be used to investigate how the Xenopus homolog of the conserved CENP-A, B, and C proteins contribute to the assembly and function of the kinetochore. Antibodies to
72 Down Syndrome
CENP-A will be used to enrich kinetochore-containing chromosome fragments, making it possible to screen large pools ol expressed cDNAs for novel kinetochore-binding proteins. Sister chromatid separation will be studied in budding yeast using green fluorescent protein (GFP) marked chromosomes. This technique will be used to, 1) investigate the length, DNA sequence, and topological features of chromosomes that are needed to establish and maintain sister chromatid linkage, 2) test the role of proximity in establishing the linkage between sisters, and 3) investigate the relationship between topological and cohesin-dependent mechanisms of sister linkage. DNA microarrays will be used to determine why topoisomerase II activity is required during anaphase to resolve sister chromatid linkage. These experiments will combine the genetic tractability of yeast and the complex in vitro reactions that are possible in frog extracts in an integrated approach to understanding mitotic chromosome behavior. This information will be directly relevant to understanding how aneuploidy is generated in Down syndrome and tumor progression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SOMATIC CELL GENETIC STUDIES OF DOWN SYNDROME Principal Investigator & Institution: Patterson, David; President and Senior Fellow; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001; Project Start 01-JAN-1993; Project End 31-DEC-2002 Summary: Affecting one in 700 live births, Down Syndrome is the major recognized genetic cause of mental retardation. It is, and expected to remain, a significant medical and social problem. While the neurological and behavioral phenotype of Down Syndrome and its genetic basis is complex, recent advances in technology, resources and knowledge mean that renal and effective progress in understanding Down Syndrome is now attainable. The immediate goal of this program project is the identification and characterization of the genes involved in the neurological, neurophysiological and behavioral phenotype of Down Syndrome. The long term goal is to apply this knowledge to the development of therapeutic interventions to ameliorate the cognitive deficits seen in Down Syndrome. The accomplishment of goals of this nature requires application of a broad spectrum of approaches, spanning molecular biology, mouse genetics and human behavior. Accordingly, this proposal will build upon the large body of information regarding Down Syndrome and human chromosome 21 compiled by this Program over the last fifteen years, and will extend its research focus in a clinically relevant direction. The specific aims of this program include: i)systematic identification and preliminary characterization of essentially all genes on chromosome 21 to determine best candidates for causation of the neurological and cognitive deficits of Down Syndrome; ii) construction and analysis of mouse models, both single gene transgenics and segmental trisomies, to test the roles of specific genes; iii) dissection of the cognitive deficits seen in individuals with Down Syndrome; iv) analysis of the behavior and physiology of relevant mouse mutants to refine understanding of the deficits seen in individuals with Down Syndrome and to define the limits of utility of mouse models; and v) design and testing in mice of new hypotheses and treatment approaches based on information obtained from the molecular, human behavior and mouse genetic data. Building on the past accomplishments and expertise of members of this program project and adding new directions and new areas of expertise makes attainment of these goals eminently feasible. Their success will add greatly to our understanding of neurological development in general and of mental retardation in Down syndrome in particular. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SPEECH OF YOUNG MALES WITH FRAGILE X SYNDROME Principal Investigator & Institution: Roberts, Joanne E. Senior Scientist and Professor; F.P. Graham Child Devel Ctr; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2003; Project Start 07-JUL-2003; Project End 30-APR-2008 Summary: (provided by applicant): Fragile X syndrome is the most common inherited cause of mental retardation, and unintelligible speech is a very common characteristics of young males with fragile X syndrome (FXS). It is unclear what aspects of speech (e.g., rate, prosody, oral structure/function, articulation, phonological processes) cause poor intelligibility. Furthermore, it has not been determined what is the role of motor speech/FMR1 protein (FMRP) levels, cognitive/linguistic factors, and the communicative context in affecting intelligibility of conversational speech of males with FXS. Identifying these factors is important because the ability to be understood is critical for effective communication, and poor speech intelligibility compromises all aspects of daily verbal interactions. The proposed study builds on a currently funded R0-3 pilot study Hearing and Speech of Young with Males with Fragile X Syndrome, funded by the RFA "Neurobiology and Genetics of Fragile X Syndrome" in April of 2001, which examined at one point in time the speech and hearing skills of young males with fragile X syndrome. The proposed research will expand this research by examining longitudinally over a five year period the factors that affect changes in the speech intelligibility of 8 to 12 year old males with FXS in comparison to developmental age matched males with Down syndrome (DS) and males who are typically developing (TD). It will identify if motor speech/FMRP levels, cognitive/linguistic factors, and the social demands of the communicative context affect speech intelligibility. The specific objectives of this study are to: a) compare the development of phonological, prosodic, and segmental factors in the speech of males with FXS, males with DS, and TD males; b) identify the phonological, prosodic, and segmental factors affecting the speech intelligibility in conversational speech of males with FXS and determine if similar patterns of association are observed among males with DS and TD males; and c) to identify the motor speech/FMRP, cognitive/linguistic, and communicative contextual factors associated with speech intelligibility in conversational speech among males with FXS, and determine if similar patterns of association are observed among males with DS and TD males. Sixty males with FXS between 8 and 12 years of age, 40 males with Down syndrome between 8 and 12 years of age and 40 typically developing males matched for nonverbal intelligence age will be followed for five years. Speech production in isolated words, imitated sentences, spontaneous conversational speech, and narratives will be examined for prosodic and segmental features, phonological processes, and speech intelligibility for the three groups. In addition, children's oral motor skills, phonological processing, and selective listening will be examined. Fragile X DNA testing and FMRP analysis from blood samples will be done only on males with FXS. Growth curve methods will be used to quantify patterns of change over time in the overall level and rate of speech development including speech intelligibility. Of particular interest will be longitudinal analyses of speech intelligibility designed to determine the degree to which motor speech/FMRP, cognitive/linguistic, and contextual factors predict speech intelligibility among males with FXS. Subsequent analyses will ask whether factors associated with intelligibility among males with FXS are also associated among males with DS and TD males. Findings will contribute to a better understanding of the factors that affect speech intelligibility in young males with FXS and provide an essential knowledge base for speech intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
74 Down Syndrome
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Project Title: STEM CELL GENES IN LEUKEMIA PATHOGENESIS Principal Investigator & Institution: Horwitz, Marshall S. Associate Professor; University of Washington Seattle, WA 98195 Timing: Fiscal Year 2001 Summary: Leukemia is a leading cause of cancer death and requires a significant expenditure of the national healthcare budget to treat. There is substantial evidence that hereditary factors contribute to leukemia predisposition and the frequently observed familial clustering and racial variations in risk. In many families, affected individuals have developed leukemias of differing type and subtype, suggesting a defect in a gene responsible for hematopoietic stem cell differentiation. A unusual of familial leukemia is that it is inherited with "anticipation" in the form of a declining age of onset with each passing generation, and we hypothesize that a defect in a mitotic clock might be responsible for this phenomenon. A locus for familial AML in association with inherited platelet defects has been mapped to chromosome 21q. Preliminary evidence suggests a second locus for familial AML on chromosome 16q in families that do not have a platelet defect. The specific aims are the following: 1) Clone the locus for familial leukemia on chromosome 21: A. Collect new individuals with the familial platelet disorder/AML syndrome, B. Narrow the critical region on chromosome 21q by studying Down syndrome patients, C. Positionally clone the chromosome 21q locus from leukemia families by mutational analysis of candidate genes from the critical region; 2) Confirm and clone a locus for familial AML on chromosome 16q: A. Use leukemia families to narrow the critical region, B. Use sporadic cases of AML and myelodysplasia to refine the critical region, C. Positionally clone the chromosome 16q AML gene; and c) Characterize the role of familial leukemia genes in hematopoietic stem cell differentiation and leukemia pathogenesis: A. Functionally characterize the genes for familial leukemia, B. Develop animal models, C. Search for common but low penetrance alleles among sporadic leukemia cases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: STUDIES ON CHILDREN WITH EARLY FOCAL BRAIN INJURY Principal Investigator & Institution: Bates, Elizabeth A. Professor; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, CA 92093 Timing: Fiscal Year 2001; Project Start 16-SEP-1985; Project End 31-JUL-2006 Summary: Over the past 15 years, we have made significant progress in the study lf language and affective development in children with congenital injuries to one side of the brain (FL). In each behavioral , we have covered evidence of initial deficits, and specific effects of lesion side and site, but these initial deficits are followed by substantial recovery and development, providing strong evidence for behavioral and neural plasticity in this population. Furthermore, we have shown that trajectories of deficit and recovery differ across domains. In language, lesion- symptom correlations exist in the first years of life, but they do not resemble the patterns observed in adults; by 5-7 years of age, specific effects of lesion side and site seem to have disappeared altogether. In spatial cognition, lesion-symptom correlations persist across childhood and adolescence, albeit in a mild form, and continue to resemble the correlations observed in adults. These results are compatible with a large literature on plasticity and reorganization in animals, supporting the view that brain development is a dynamic, responsive and selforganizing system. But they also offer a unique perspective on plasticity and brain organization in humans. We are now well-positioned to take a historic new steps, with convergent use of functional magnetic resonance imaging (fMRI), event-related brain
Studies 75
potentials(ERP), combined with analogous "on-line" (timed" behavioral studies of language, spatial cognition and spatial attention. These convergent methods will yield unprecedented information about the "alternative brain plans" that have emerged across the course of development in children with FL. E will also continue to chart language and cognitive development into adolescence, using benchmark "off-line" (untimed" measures of language (including aspects of discourse that re critical to success in school and work), visual-spatial cognition, memory and executive function. On all measures, results for children with FL will be compared systematically to findings for children in other populations, including Specific Language Impairment, Williams Syndrome, Down Syndrome, and new project studying other forms of FL. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STUDY ON A NOVEL ALZHEIMER APP REGULATORY FACTOR Principal Investigator & Institution: Quitschke, Wolfgang W. Psychiatry and Behavioral Scis; State University New York Stony Brook Stony Brook, NY 11794 Timing: Fiscal Year 2002; Project Start 01-JUL-1992; Project End 30-NOV-2006 Summary: (provided by the applicant): An important neuropathological manifestation of Alzheimer's disease is the presence of amyloid depositions in brains and leptomeninges of afflicted individuals. However, amyloid depositions are not unique to Alzheimer's disease. They also occur in Down syndrome and hereditary cerebral hemorrhage with amyloidosis of the Dutch type and to a lesser degree in the normal aging brain. A major component of the amyloid plaque is the amyloid f3-protein (AB). This peptide is derived from a larger protein termed the amyloid precursor protein (APP) through proteolytic processing. Several lines of genetic evidence indicate that the pathological manifestations of Alzheimer's disease are a direct consequence of the deposition of AB. In addition, increased or altered APP expression, such as in Down syndrome, may be an important factor in a multistep process leading to the formation of amyloid deposits. This suggests that the progression of the disease might be delayed or arrested by reducing or eliminating APP expression and it emphasizes the importance of elucidating the mechanism of APP gene regulation. A sequence element in the proximal promoter region was found to be essential for high levels of expression. This element binds the multivalent and multifunctional transcription factor CTCF, which acts as a transcriptional activator. The precise region within the CTCF protein that mediates transcriptional activation will be identified by deletion and mutation analysis. The coactivator(s) that interacts with CTCF will be identified. In addition, further essential factors that encompass the transcription complex of the APP promoter will be identified. These include the components of the transcriptional initiation complex and other as yet uncharacterized APP promoter binding factors. Finally, the nucleosomal organization of the APP promoter will be examined for a better understanding of APP gene regulation in vivo. One ultimate goal of this research is to control APP gene expression in vivo by altering the interaction of activating factors with the APP promoter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: SYNAPTIC PLASTICITY IN MOUSE MODELS FOR DOWN SYNDROME Principal Investigator & Institution: Costa, Alberto C.; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2001; Project Start 01-MAR-2000; Project End 28-FEB-2003
76 Down Syndrome
Summary: (adapted from applicant's abstract) Down syndrome is the most common genetically defined cause of mental retardation in human beings. There are about 250 thousand people with DS in the US and this number is likely to continue rising due to the current trend towards an increased life expectancy. In general, the cells of individuals with DS have one extra chromosome 21. This genetic condition affects the nervous system in many different ways besides producing different degrees of mental retardation. Individuals with DS have an increased incidence of seizure disorders and exhibit abnormalities of neuromuscular tone, audiovestibular function, ocular movements and visual acuity. They also develop a neuropathology indistinguishable from Alzheimer's disease after the third decade of life. Currently, Ts65Dn mice are the prime animal model for the mental deficit in DS. These mice are trisomic for a chromosomal segment homologous to a large portion of human chromosome 21. In behavioral tests, Ts65Dn mice display significant learning deficits. More recently, another partially trisomic mouse model for DS, called Ts1Cje, has been described. It has a trisomic segment only slightly shorter than the Ts65Dn segment and a comparatively milder learning deficit. The overall hypothesis is that the region of difference between the trisomic segments of these two mouse strains may contain genes responsible for a significant portion of the learning deficit seen in Ts65Dn mice, and possibly in persons with DS. The identification of such genes may provide targets for a rational pharmacotherapy for DS. This proposal has three specific aims: 1) Test the hypothesis that some forms of synaptic plasticity are selectively altered in aneuploid mouse models for DS; 2) Test the hypothesis that dendritic morphology is altered in mouse models for DS; 3) Test the hypothesis that three copies of specific single genes are necessary for the expression of part of the learning deficit seen in Ts65Dn mice by analyzing the phenotype of crosses between Ts65Dn and knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE BIOLOGY OF CHROMOSOME 21 GENES: R13 EXPERT WORKSHOP Principal Investigator & Institution: Gardiner, Katheleen; Senior Scientist; Eleanor Roosevelt Inst for Cancer Res 1899 Gaylord St Denver, CO 80206 Timing: Fiscal Year 2003; Project Start 18-SEP-2003; Project End 31-MAY-2004 Summary: [Provided by Applicant]: To create new research directions and opportunities for collaborations in the study of Down syndrome, there is a need to bring together two groups of investigators: (1) those studying human chromosome 21 and Down syndrome and its mouse models, and (2) those studying the biology and/or the molecular biology of specific genes that map to chromosome 21 or specific pathways or processes whose components map to chromosome 21. The first group includes experts on chromosome 21 who have been involved in the mapping, sequencing, and annotation of chromosome 21 and its homologous mouse genomic regions, the identification and expression analysis of chromosome 21 and its homologous mouse genes, the creation and analysis of mouse models of Down syndrome, both segmental trisomies and transgenics, and the definition of the human Down syndrome phenotype. Members of the second group not involved in Down syndrome research may not even be aware that their work can impact Down syndrome research. They are studying individual genes or family members such as transcription factors, transcription regulators, or ion channel genes that map to chromosome 21, or processes such as the ubiquitin proteasome pathway, RNA processing, tight junctions and cell adhesion, or the MAP kinase pathway, each of which has several component or modulating genes mapping to chromosome 21. This application requests funding to cover venue and travel expenses for a workshop to
Studies 77
bring together approximately 30 established chromosome 21/Down syndrome investigators with approximately 30 non-Down syndrome but chromosome 21 gene experts to discuss the biology of chromosome 21-encoded genes and the implications for their overexpression in the Down syndrome phenotype. The meeting will be held for three days in Washington, DC within a timeframe of five months after the availability of funding. It is anticipated that this workshop will generate new and testable theories for gene-phenotype correlations in Down syndrome, foster new collaborations, and introduce new researchers with novel expertise to the Down syndrome research field. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: THE DEVELOPMENT OF JOINT ATTENTION AFTER INFANCY Principal Investigator & Institution: Adamson, Lauren B. Professor; Psychology; Georgia State University University Plaza Atlanta, GA 30303 Timing: Fiscal Year 2002; Project Start 05-APR-1998; Project End 31-MAR-2007 Summary: (provided by applicant): The long-term goal of this project is to trace the developmental course of shared attention between young children and their social partners. Our central argument is that the scope and organization of shared attention is transformed repeatedly as children acquire new ways to coordinate actions and represent events Our current longitudinal research examines the transformation of joint attention that occurs as typically developing toddlers become increasingly competent symbol users, and it documents how this process is impacted by autism, a developmental disorder characterized by joint attention deficits. In this continuation application, we pursue three aims: to relate variations in the trajectory of joint attention development to individual differences in typically developing children's propensities to engage with people and with objects; to describe further atypical patterns of joint attention development that may reflect extreme variations in object and social orientation and in language acquisition; and to continue to trace joint attention development after infancy into the preschool years as new representational skills are mastered. We continue to observe 48 typically developing children and 24 children with autism who are currently enrolled in the project, and we recruit 48 new participants, half of whom have Down syndrome and half who are late talkers. Each child and mother is videotaped 8 times in a Communication Play. The first five visits occur during a one year interval so that we can trace the emergence of symbol-infused joint attention during interactions that focus on requesting, social interacting, shared referring, and discussing past and future. The last three visits occur at age 3-1/2, 4-1/2 and 5-1/2 and probe the emergence of language mediated joint attention during interactions that focus on internal states, narrating the past and future, and graphic symbols. The rate of language acquisition and interests in objects and social domains are also assessed. Videotapes will be transcribed and coded to document the child's attention to people, objects, and symbols; the child's symbolic actions; and the mother's attention-directing actions toward symbols. Growth curves will be examined to chart the course of joint attention as a function of language onset and child orientation to people and to objects. This systematic longitudinal study of developmental changes in shared attention will provide a fuller view of how children are introduced to symbols as they communicate with their caregivers and how symbols expand the scope and affect the organization of shared attention. This view should further the formulation of models of representational development from infancy through early childhood as well as inform understandings of developmental disorders such as autism, Down syndrome, and late speech onset. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE TEMPORAL COORDINATION IN INFANT SOCIAL ACTIONS Principal Investigator & Institution: Messinger, Daniel S. Psychology; University of Miami Box 016159 Miami, FL 33101 Timing: Fiscal Year 2001; Project Start 01-AUG-2000; Project End 31-JUL-2003 Summary: Before the onset of speech, an index of the developing communicative significance of infant social actions is their temporal coordination. One type of temporal coordination occurs when an action (e.g., a vocalization) both begins and ends during the course of another (e.g., a gaze at mother). This pattern of temporal embedding suggests the two actions are part of a single expressive event. The proposed project will use a new software simulation bootstrapping procedure to document embedding and other patterns in the temporal coordination of infant social actions. 50 infants will be observed longitudinally at 3, 6, and 9 months interacting with their mothers in a face-toface still- face procedure. Descriptive coding will be used to categorize infant vocalizations and facial expressions by affective tone. Direction of infant gaze will be coded as at mother's face/eyes or away. Patterns of reciprocal embedding are hypothesized for actions in all pairs of behavioral modalities. Infants are expected, for example, to begin and end facial expressions in the course of a gaze at mother's face; but they are also expected to begin and end gazes at mother in the course of a facial expression. Software incorporating a bootstrapping procedure simulates the temporal progression of infant actions independently within each modality, creating multiple simulated sessions with random levels of between modality coordination. It will indicate whether infants reciprocally embed social actions at greater than chance levels. Increases in temporal embedding are expected with age as infants become more competent communicators. Decreases in embedding are expected when infant's are frustrated by maternal non-responsiveness in the still face procedure. The relative strength of embedded patterns involving effectively positive and negative actions will be contrasted to shed light on their respective expressive clarity. In sum, a new approach will be used to determine whether embedded events occur at greater than chance levels 1) overall, 2) during interaction rather than a maternal still-face, 3) at different ages, and 4) among different effectively toned pairs of social actions. A long term objective of the project is to gather pilot data for future investigations of temporal coordination between infant and mother (e.g., turn-taking). This will open the way for exploration of coordination deficits stemming from infant communicative disorders such as autism and Down syndrome, as well as coordination deficits stemming from maternal risk factors such as depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TRANSGENIC MOUSE MODEL OF INCLUSION BODY MYOSITIS Principal Investigator & Institution: Laferla, Frank M. Assistant Psychobiology; University of California Irvine Campus Dr Irvine, CA 92697
Professor;
Timing: Fiscal Year 2001; Project Start 15-APR-1998; Project End 28-FEB-2002 Summary: The overall long-term objective of this FIRST proposal is to understand the molecular pathogenesis of inclusion body myositis (IBM), the most common muscle disease in personals over 50 years of age. Although the cause of this disease remains to be determined, surprisingly it has recently been observed that many of the biochemical features that occur in brains afflicted with Alzheimer's disease also occur in IBM. The Alzheimer's disease brain is characterized by diffuse and neuritic plaques, the hallmark structures of this insidious disease. The principal constituent of these plaques is a small peptide called beta-amyloid. Various histochemical and immunological reagents have
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been used to show that beta-amyloid deposits accumulate in affected muscle fibers in IBM. Consequently, IBM represents the first disease, other than those disorders related to Alzheimer's disease such as Down syndrome and vascular dementia, where pathological accumulation of the beta-amyloid peptide occurs outside the central nervous system. Notably, the accumulation of beta-amyloid appears to be a specific component of IBM since this peptide is not present in other muscle disorders. This finding is significant and suggests a pathophysiological role for beta-amyloid in this common, age- related myopathy. The observation that beta-amyloid accumulates in inclusion body myositis represents an important opportunity to study the role that this peptide plays in this muscular disorder. For this application, three specific aims are proposed: [1] to investigate the pathophysiological role of beta-amyloid accumulation in skeletal muscle tissue we will derive transgenic mice that selectively over-produce this peptide. The muscle creatine kinase promotor, which has been used by other investigators to direct expression to skeletal muscle of transgenic mice, will be used to specifically target transgenes to these tissues. These mice will allow us to test the hypothesis that beta-amyloid accumulation in muscle leads to pathological changes resembling IBM and provide insights into the pathophysiological role of this peptide in muscle. [2] Another transgenic mouse model will also be derived in which the betaamyloid pre-cursor protein, the molecule from which beta-amyloid is derived. will be over-produced in muscle; these mice will allow us to test the hypothesis that increased expression of the pre-cursor molecule leads to unmanageable levels of beta-amyloid. Not only would such animal models be useful for studying an age-related muscle disease like IBM, but they may also provide relevant insights into the pathophysiological role these proteins play in Alzheimer's disease as well. [3] Recent evidence from our laboratory suggests that herpes virus, which we found contains a viral protein with shared homology and activity to beta-amyloid, may act as a cofactor for AD. In view of the many parallels between AD and IBM and the prominent role that beta-amyloid plays in IBM, we will investigate in herpes virus may also act as a cofactor in the pathogenesis of IBM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRISOMY NONDISJUNCTION
21:
RISK
FACTORS
FOR
CHROMOSOME
Principal Investigator & Institution: Sherman, Stephanie L. Professor of Human Genetics; Genetics; Emory University 1784 North Decatur Road Atlanta, GA 30322 Timing: Fiscal Year 2001; Project Start 22-JUN-2000; Project End 31-MAY-2005 Summary: Although the chromosomal basis of Down syndrome (DS) has been known for over 30 years, there is still a surprising lack of knowledge about causes of nondisjunction leading to trisomy 21, or to any other human trisomy. Also, little is known about risk factors that predispose DS individuals to specific birth defects. Based on our ongoing studies, we have identified important correlates to nondisjunction. We have found strong evidence that altered recombination along the nondisjoined chromosome 21 is associated with increased risk for all types of meiotic errors. New data suggest that this altered recombination may be a cell- wide phenomenon. Our preliminary analyses of environmental factors suggest that smoking and oral contraceptive use around the time of conception may predispose to one specific type of nondisjunction error, implying that risk factors affect different stages of meiosis. The success of our current studies has resulted from the combined use of cytogenetic, molecular, and epidemiological methods to study DS not as a single entity, but as subgroups defined by the type of error. We propose to extend these studies to
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investigate: 1) the relationship of altered recombination and maternal age; 2) individual variation in cell- wide recombination as a risk factor for nondisjunction; 3) the role of recombination in paternal nondisjunction; and 4) environmental and maternal risk factors for nondisjunction and for DS-associated birth defects. These specific aims require a substantial increase in the study population. We have a unique opportunity to ascertain over 1350 cases of trisomy 21 from well- established birth defect surveillance systems using the infrastructure established by the National Birth Defects Prevention Study. Six of the study sites (AR, CA, GA, IA, NJ, NY) will contribute a populationbased sample of cases and controls. All sites are experienced in identifying, tracking, interviewing, and collecting biological samples from families with birth defects. The data resulting from this proposal will provide a valuable resource to uncover the etiology and consequences of nondisjunction of chromosome 21. These studies parallel those on other significant trisomies proposed by Dr. Terry Hassold in the companion IRPG application. Indeed, the questions and methodological approaches are nearly identical. By combining a large, population-based analysis of trisomy 21 with analyses of other autosomal and sex chromosome trisomies, we intend to characterize the genesis of the most common and clinically important human chromosome abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: VOCABULARY EXPANSION IN SEVERE MENTAL RETARDATION Principal Investigator & Institution: Wilkinson, Krista M. Eunice Kennedy Shriver Center; Univ of Massachusetts Med Sch Worcester Office of Research Funding Worcester, MA 01655 Timing: Fiscal Year 2001; Project Start 01-APR-1998; Project End 31-MAR-2003 Summary: In typically-developing children initially slow, one-at-a-time word learning is followed by an apparent explosion in their lexicon. One estimate suggests that children are learning up to nine new words a day. By contrast, for some individuals with severe mental retardation new words enter the lexicon only through slow and deliberate effort. Yet word learning is a foundational component of human development, necessary for advanced linguistic functions and contributing to complex representational skills (e.g., categorization). To the extent that a cognitive disability interferes with word learning, progress in these domains will be correspondingly limited. It is therefore essential to explore in detail the nature of lexical impairments in severe mental retardation. The existence of difficulties in lexical acquisition among individuals with severe mental retardation raises important questions. When rapid vocabulary expansion occurs, what linguistic cognitive processes support that learning? When it does not occur, what skills are deficient or absent? A phenomenon called fast mapping may be of greatest potential relevance for rapid vocabulary expansion. Fast mapping refers to a quick, initial partial understanding of a new word's meaning derived from the context of word use. Fast mapping has been argued to facilitate the vocabulary explosion. This proposed role has received empirical confirmation in typical youngsters and children with Down syndrome. Yet evidence from children with atypical cognition/language has recently challenged the universality of this relation. The Principal Investigator's studies have added to the preliminary evidence of selective deficits in fast mapping among individuals with severe mental retardation, William's syndrome, or specific language impairments. The deficits are most often observed when individuals attempt to apply the principle for the purpose of vocabulary expansion. These recent findings oblige a more systematic analysis of the precise role of the principle in learning outcomes in mental retardation. Is fast mapping at risk in individuals with severe mental retardation, potentially limiting their vocabulary expansion? This application proposes a five-year
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study of vocabulary expansion and delay, focusing specifically on rapid expansion of an extant, but limited, vocabulary. The proposed series of studies will implement methods developed by the Principal Investigator that will enable the systematic analysis of unresolved questions of lexical expansion in severe mental retardation. The project has four specific aims that will be addressed in the course of four studies: 1) To examine the relation of fast mapping, rapid vocabulary expansion, and nonverbal processes, in order to explore the nature of lexical expansion in severe mental retardation; 2) To explore the points of greatest vulnerability for learning through fast mapping by explicitly taxing participants' skills and observing the ways in which breakdowns occur; 3) To extend the analysis from the commonly examined object-word learning to the acquisition of actionrelated words, to determine whether processes of fast mapping are similar for the two types of form/class categories; 4) To examine the basis underlying children's apparent assumption that new words should and do map to unnamed objects, and whether this assumption is intact among individuals with severe mental retardation. 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 “Down syndrome” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Down syndrome in the PubMed Central database: •
Cerebral cortical astroglia from the trisomy 16 mouse, a model for Down syndrome, produce neuronal cholinergic deficits in cell culture. by Nelson PG, Fitzgerald S, Rapoport SI, Neale EA, Galdzicki Z, Dunlap V, Bowers L, v. Agoston D. 1997 Nov 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=25068
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Chromosomal Protein HMG-14 Gene Maps to the Down Syndrome Region of Human Chromosome 21 and Is Overexpressed in Mouse Trisomy 16. by Pash J, Popescu N, Matocha M, Rapoport S, Bustin M. 1990 May 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=53998
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Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome. by Holtzman DM, Santucci D, Kilbridge J, Chua-Couzens J, Fontana DJ, Daniels SE, Johnson RM, Chen K, Sun Y, Carlson E, Alleva E, Epstein CJ, Mobley WC. 1996 Nov 12; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=24093
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Down Syndrome Phenotypes: The Consequences of Chromosomal Imbalance. by Korenberg JR, Chen X, Schipper R, Sun Z, Gonsky R, Gerwehr S, Carpenter N, Daumer
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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C, Dignan P, Disteche C, Graham JM Jr, Hudgins L, McGillivray B, Miyazaki K, Ogasawara N, Park JP, Pagon R, Pueschel S, Sack G, Say B, Schuffenhauer S, Soukup S, Yamanaka T. 1994 May 24; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=43917 •
Down Syndrome-Critical Region Contains a Gene Homologous to Drosophila sim Expressed During Rat and Human Central Nervous System Development. by Dahmane N, Charron G, Lopes C, Yaspo M, Maunoury C, Decorte L, Sinet P, Bloch B, Delabar J. 1995 Sep 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=40950
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Quantitative analysis of DNA levels in maternal plasma in normal and Down syndrome pregnancies. by Hromadnikova I, Houbova B, Hridelova D, Voslarova S, Calda P, Nekolarova K, Kofer J, Stejskal D, Doucha J, Cinek O, Vavrirec J. 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116571
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Quantitative Analysis of Senile Plaques in Alzheimer Disease: Observation of LogNormal Size Distribution and Molecular Epidemiology of Differences Associated with Apolipoprotein E Genotype and Trisomy 21 (Down Syndrome). by Hyman BT, West HL, Rebeck GW, Buldyrev SV, Mantegna RN, Ukleja M, Havlin S, Stanley HE. 1995 Apr 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=42212
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The sequence of human chromosome 21 and implications for research into Down syndrome. by Gardiner K, Davisson M. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=138845
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Ts1Cje, a partial trisomy 16 mouse model for Down syndrome, exhibits learning and behavioral abnormalities. by Sago H, Carlson EJ, Smith DJ, Kilbridge J, Rubin EM, Mobley WC, Epstein CJ, Huang TT. 1998 May 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27649
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Unusual Association of Hypertrophic Cardiomyopathy with Complete Atrioventricular Canal Defect and Down Syndrome. by Eidem BW, Jones C, Cetta F. 2000; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101082
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. 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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To generate your own bibliography of studies dealing with Down syndrome, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Down syndrome” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Down syndrome (hyperlinks lead to article summaries): •
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study. Author(s): Prasher VP, Huxley A, Haque MS; Down syndrome Ageing Study Group. Source: International Journal of Geriatric Psychiatry. 2002 March; 17(3): 270-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11921156&dopt=Abstract
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A combination of physical examination and ECG detects the majority of hemodynamically significant heart defects in neonates with Down syndrome. Author(s): Shashi V, Berry MN, Covitz W. Source: American Journal of Medical Genetics. 2002 March 15; 108(3): 205-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891686&dopt=Abstract
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A dorsal root ganglia cell line derived from trisomy 16 fetal mice, a model for Down syndrome. Author(s): Allen DD, Cardenas AM, Arriagada C, Bennett LB, Garcia CJ, Caviedes R, Rapoport SI, Caviedes P. Source: Neuroreport. 2002 March 25; 13(4): 491-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11930168&dopt=Abstract
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A Down syndrome case with a karyotype of 46,XY,rec(21)dup(21q)inv(21)(p11q22) derived from paternal pericentric inversion of chromosome 21. Author(s): Ilgin Ruhi H, Tukun A, Karabulut H, Bayazit P, Bokesoy I. Source: Clinical Genetics. 2001 May; 59(5): 368-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359472&dopt=Abstract
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A Down syndrome patient treated by peritoneal dialysis. Author(s): Hausmann MJ, Landau D. Source: Nephron. 2002 October; 92(2): 484-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12218338&dopt=Abstract
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A histological and radiological investigation of the nasal bone in fetuses with Down syndrome. Author(s): Tuxen A, Keeling JW, Reintoft I, Fischer Hansen B, Nolting D, Kjaer I. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 July; 22(1): 22-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858297&dopt=Abstract
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A neolithic case of Down syndrome. Author(s): Diamandopoulos AA, Rakatsanis KG, Diamantopoulos N. Source: Journal of the History of the Neurosciences. 1997 April; 6(1): 86-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11619201&dopt=Abstract
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A new age for childhood diseases. Down syndrome. Author(s): Finesilver C. Source: Rn. 2002 November; 65(11): 43-8; Quiz 49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12465526&dopt=Abstract
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A new gene family including DSCR1 (Down Syndrome Candidate Region 1) and ZAKI-4: characterization from yeast to human and identification of DSCR1-like 2, a novel human member (DSCR1L2). Author(s): Strippoli P, Lenzi L, Petrini M, Carinci P, Zannotti M. Source: Genomics. 2000 March 15; 64(3): 252-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10756093&dopt=Abstract
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A novel gene, DSCR5, from the distal Down syndrome critical region on chromosome 21q22.2. Author(s): Togashi T, Choi DK, Taylor TD, Suzuki Y, Sugano S, Hattori M, Sakaki Y. Source: Dna Res. 2000 June 30; 7(3): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907851&dopt=Abstract
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A novel mutation in the endothelin B receptor gene in a patient with ShahWaardenburg syndrome and Down syndrome. Author(s): Boardman JP, Syrris P, Holder SE, Robertson NJ, Carter N, Lakhoo K. Source: Journal of Medical Genetics. 2001 September; 38(9): 646-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11565556&dopt=Abstract
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A paravertebral neoplasm in a child with Down syndrome. Author(s): Satge D, Rubie H, Sommelet D. Source: Pediatric Surgery International. 2001 September; 17(7): 588. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11666071&dopt=Abstract
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A protein encoded within the Down syndrome critical region is enriched in striated muscles and inhibits calcineurin signaling. Author(s): Rothermel B, Vega RB, Yang J, Wu H, Bassel-Duby R, Williams RS. Source: The Journal of Biological Chemistry. 2000 March 24; 275(12): 8719-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10722714&dopt=Abstract
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A t(1;22)(p13;q13) in four children with acute megakaryoblastic leukemia (M7), two with Down syndrome. Author(s): Trejo RM, Aguilera RP, Nieto S, Kofman S. Source: Cancer Genetics and Cytogenetics. 2000 July 15; 120(2): 160-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942809&dopt=Abstract
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A unique downregulation of h2-calponin gene expression in Down syndrome: a possible attenuation mechanism for fetal survival by methylation at the CpG island in the trisomic chromosome 21. Author(s): Kuromitsu J, Yamashita H, Kataoka H, Takahara T, Muramatsu M, Sekine T, Okamoto N, Furuichi Y, Hayashizaki Y. Source: Molecular and Cellular Biology. 1997 February; 17(2): 707-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9001224&dopt=Abstract
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Aberrant expression of centractin and capping proteins, integral constituents of the dynactin complex, in fetal down syndrome brain. Author(s): Gulesserian T, Kim SH, Fountoulakis M, Lubec G. Source: Biochemical and Biophysical Research Communications. 2002 February 15; 291(1): 62-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11829462&dopt=Abstract
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Aberrant expression of dihydropyrimidinase related proteins-2,-3 and -4 in fetal Down syndrome brain. Author(s): Weitzdoerfer R, Fountoulakis M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 95-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771764&dopt=Abstract
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Aberrant expression of signaling-related proteins 14-3-3 gamma and RACK1 in fetal Down syndrome brain (trisomy 21). Author(s): Peyril A, Weitzdoerfer R, Gulesserian T, Fountoulakis M, Lubec G. Source: Electrophoresis. 2002 January; 23(1): 152-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824616&dopt=Abstract
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Abnormal TGFbeta levels in the amniotic fluid of Down syndrome pregnancies. Author(s): Bromage SJ, Lang AK, Atkinson I, Searle RF. Source: American Journal of Reproductive Immunology (New York, N.Y. : 1989). 2000 October; 44(4): 205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076091&dopt=Abstract
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Absence of association of fetal MTHFR C677T polymorphism with prenatal Down syndrome pregnancies. Author(s): Yanamandra K, Bocchini JA Jr, Thurmon TF. Source: European Journal of Human Genetics : Ejhg. 2003 January; 11(1): 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12529699&dopt=Abstract
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Acanthosis nigricans: a new cutaneous sign in severe atopic dermatitis and Down syndrome. Author(s): Munoz-Perez MA, Camacho F. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2001 July; 15(4): 325-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730043&dopt=Abstract
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Acceptability of serum screening as an alternative to cytogenetic diagnosis of down syndrome among women 35 years or older in Hong Kong. Author(s): Lam YH, Tang MH, Lee CP, Sin SY, Tang R, Wong HS, Wong SF. Source: Prenatal Diagnosis. 2000 June; 20(6): 487-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10861714&dopt=Abstract
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Acceptance of screening and abortion for Down syndrome among Finnish midwives and public health nurses. Author(s): Jallinoja P, Santalahti P, Toiviainen H, Hemminki E. Source: Prenatal Diagnosis. 1999 November; 19(11): 1015-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589051&dopt=Abstract
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Accommodation and refractive error in children with Down syndrome: crosssectional and longitudinal studies. Author(s): Cregg M, Woodhouse JM, Pakeman VH, Saunders KJ, Gunter HL, Parker M, Fraser WI, Sastry P. Source: Investigative Ophthalmology & Visual Science. 2001 January; 42(1): 55-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11133848&dopt=Abstract
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Accuracy and cost-effectiveness of a new strategy to screen for celiac disease in children with Down syndrome. Author(s): Csizmadia CG, Mearin ML, Oren A, Kromhout A, Crusius JB, von Blomberg BM, Pena AS, Wiggers MN, Vandenbroucke JP. Source: The Journal of Pediatrics. 2000 December; 137(6): 756-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113830&dopt=Abstract
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Accuracy of expected risk of Down syndrome using the second-trimester triple test. Author(s): Meier C, Huang T, Wyatt PR, Summers AM. Source: Clinical Chemistry. 2002; 48(4): 653-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11901067&dopt=Abstract
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Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Author(s): Wechsler J, Greene M, McDevitt MA, Anastasi J, Karp JE, Le Beau MM, Crispino JD. Source: Nature Genetics. 2002 September; 32(1): 148-52. Epub 2002 August 12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172547&dopt=Abstract
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Acute megakaryoblastic leukemia in Down syndrome: orbital infiltration. Author(s): Olson JL, May MJ, Stork L, Kadan N, Bateman JB. Source: American Journal of Ophthalmology. 2000 July; 130(1): 128-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11004278&dopt=Abstract
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Acute plasmacytic interstitial nephritis in a child with Down syndrome. Author(s): Al-Hermi BE, Thorner PS, Arbus GS. Source: Pediatric Nephrology (Berlin, Germany). 1999 May; 13(4): 333-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454785&dopt=Abstract
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Adaptive behavior and cognitive function of adults with down syndrome: modeling change with age. Author(s): Hawkins BA, Eklund SJ, James DR, Foose AK. Source: Mental Retardation. 2003 February; 41(1): 7-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597720&dopt=Abstract
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Advances in antenatal screening for Down syndrome. Author(s): Wald NJ, Hackshaw AK. Source: Bailliere's Best Practice & Research. Clinical Obstetrics & Gynaecology. 2000 August; 14(4): 563-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10985931&dopt=Abstract
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Advances in prenatal screening for Down syndrome: II first trimester testing, integrated testing, and future directions. Author(s): Benn PA. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 2002 October; 324(1-2): 1-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12204419&dopt=Abstract
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Adverse effects of phenytoin given for late-onset seizures in adults with Down syndrome. Author(s): Tsiouris JA, Patti PJ, Tipu O, Raguthu S. Source: Neurology. 2002 September 10; 59(5): 779-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12221182&dopt=Abstract
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Allele varepsilon4 of apolipoprotein E gene is less frequent in Down syndrome patient of the Sicilian population and has no influence on the grade of mental retardation. Author(s): Anello G, Gueant J, Romano C, Barone C, Pettinato R, Pillot T, Rodriguez R, Romano A, Bosco P. Source: Neuroscience Letters. 2001 June 22; 306(1-2): 129-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403974&dopt=Abstract
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Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome. Author(s): Dierssen M, Vallina IF, Baamonde C, Garcia-Calatayud S, Lumbreras MA, Florez J. Source: Brain Research. 1997 February 28; 749(2): 238-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9138724&dopt=Abstract
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Altered gene expression in fetal Down syndrome brain as revealed by the gene hunting technique of subtractive hybridization. Author(s): Kitzmueller E, Labudova O, Rink H, Cairns N, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 99-124. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666671&dopt=Abstract
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Altered glutamate uptake in peripheral tissues from Down syndrome patients. Author(s): Begni B, Brighina L, Fumagalli L, Andreoni S, Castelli E, Francesconi C, Del Bo R, Bresolin N, Ferrarese C. Source: Neuroscience Letters. 2003 June 5; 343(2): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759167&dopt=Abstract
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Alu-splice cloning of human Intersectin (ITSN), a putative multivalent binding protein expressed in proliferating and differentiating neurons and overexpressed in Down syndrome. Author(s): Pucharcos C, Fuentes JJ, Casas C, de la Luna S, Alcantara S, Arbones ML, Soriano E, Estivill X, Pritchard M. Source: European Journal of Human Genetics : Ejhg. 1999 September; 7(6): 704-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10482960&dopt=Abstract
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Alzheimer's disease and down syndrome: from meiosis to dementia. Author(s): Petronis A. Source: Experimental Neurology. 1999 August; 158(2): 403-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10415146&dopt=Abstract
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Ambiguity of the external genitalia in an infant with Down syndrome: gender assignment and ethical implications. Author(s): Jospe N, Lane A, Greenlaw J, Sulkes SB. Source: Mental Retardation. 1999 June; 37(3): 232-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10473342&dopt=Abstract
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American Academy of Pediatrics: Health supervision for children with Down syndrome. Author(s): American Academy of Pediatrics. Committee on Genetics. Source: Pediatrics. 2001 February; 107(2): 442-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11158488&dopt=Abstract
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Amygdala and hippocampal volumes in children with Down syndrome: a highresolution MRI study. Author(s): Pinter JD, Brown WE, Eliez S, Schmitt JE, Capone GT, Reiss AL. Source: Neurology. 2001 April 10; 56(7): 972-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11294940&dopt=Abstract
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An angel with Down syndrome in a sixteenth century Flemish Nativity painting. Author(s): Levitas AS, Reid CS. Source: American Journal of Medical Genetics. 2003 February 1; 116A(4): 399-405. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522800&dopt=Abstract
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An association of congenital mid-tracheal stenosis with Down syndrome. Author(s): Weber TR, Fiore A. Source: Surgery. 2000 March; 127(3): 358-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10715996&dopt=Abstract
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An infant with Down syndrome and retinoblastoma. A possible non-fortuitous association. Author(s): Moll AC, Imhof SM, Bouter L, den Otter W, Koten JW. Source: Ophthalmic Genetics. 2002 June; 23(2): 135-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187432&dopt=Abstract
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An infant with Down syndrome and retinoblastoma. A possible non-fortuitous association. Author(s): Satge D, Gembara P, Sasco AJ, Francannet C, Desjardins L, Vekemans M, Demeocq F. Source: Ophthalmic Genetics. 2001 June; 22(2): 117-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449321&dopt=Abstract
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An overview and update regarding medical problems in Down syndrome. Author(s): Grech V. Source: Indian J Pediatr. 2001 September; 68(9): 863-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11669035&dopt=Abstract
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Analysis of ankle kinetics during walking in individuals with Down syndrome. Author(s): Cioni M, Cocilovo A, Rossi F, Paci D, Valle MS. Source: Am J Ment Retard. 2001 September; 106(5): 470-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11531465&dopt=Abstract
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Animal models of Down syndrome. Author(s): Kola I, Pritchard M. Source: Molecular Medicine Today. 1999 June; 5(6): 276-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10475712&dopt=Abstract
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Aniridia and Down syndrome. Author(s): Cela E, BenEzra D. Source: Journal of Pediatric Ophthalmology and Strabismus. 2000 November-December; 37(6): 369-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392414&dopt=Abstract
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Annotation of human chromosome 21 for relevance to Down syndrome: gene structure and expression analysis. Author(s): Gardiner K, Slavov D, Bechtel L, Davisson M. Source: Genomics. 2002 June; 79(6): 833-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036298&dopt=Abstract
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Antenatal Down syndrome screening in the United States in 2001: a survey of maternal-fetal medicine specialists. Author(s): Egan JF, Kaminsky LM, DeRoche ME, Barsoom MJ, Borgida AF, Benn PA. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 1230-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439510&dopt=Abstract
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Antioxidant proteins in fetal brain: superoxide dismutase-1 (SOD-1) protein is not overexpressed in fetal Down syndrome. Author(s): Gulesserian T, Engidawork E, Fountoulakis M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 71-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771762&dopt=Abstract
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Antioxidant system in Down syndrome: a possible role in cataractogenesis. Author(s): Cengiz M, Seven M, Suyugul N. Source: Genet Couns. 2002; 13(3): 339-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12416643&dopt=Abstract
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Antiphospholipid antibodies and Down syndrome: a case series. Author(s): Requena-Silla Y, Rosenfield CG, Miller LC. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2002 October; 24(7): 575-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12368700&dopt=Abstract
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Antiphospholipid antibodies and stroke in Down syndrome. Author(s): Gatenby P, Tucko R, Andrews C, O'Neil R. Source: Lupus. 2003; 12(1): 58-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587828&dopt=Abstract
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APOE genotype and gender effects on Alzheimer disease in 100 adults with Down syndrome. Author(s): Lai F, Kammann E, Rebeck GW, Anderson A, Chen Y, Nixon RA. Source: Neurology. 1999 July 22; 53(2): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430422&dopt=Abstract
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App gene dosage modulates endosomal abnormalities of Alzheimer's disease in a segmental trisomy 16 mouse model of down syndrome. Author(s): Cataldo AM, Petanceska S, Peterhoff CM, Terio NB, Epstein CJ, Villar A, Carlson EJ, Staufenbiel M, Nixon RA. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 July 30; 23(17): 6788-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890772&dopt=Abstract
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Appropriate biochemical parameters in first-trimester screening for Down syndrome. Author(s): Cuckle HS, van Lith JM. Source: Prenatal Diagnosis. 1999 June; 19(6): 505-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10416963&dopt=Abstract
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Are the strokes in moyamoya syndrome associated with Down syndrome due to protein C deficiency? Author(s): Gururaj A, Hardy D, Al-Gazali LI, Sztriha L, Roos A, Nork M. Source: Brain & Development. 2002 October; 24(7): 719-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12427521&dopt=Abstract
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Aspects of intracranial and spinal tumors in patients with Down syndrome and report of a rapidly progressing Grade 2 astrocytoma. Author(s): Satge D, Monteil P, Sasco AJ, Vital A, Ohgaki H, Geneix A, Malet P, Vekemans M, Rethore MO. Source: Cancer. 2001 April 15; 91(8): 1458-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301393&dopt=Abstract
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Assessment of the value of reporting partial screening results in prenatal screening for Down syndrome. Author(s): Hackshaw AK, Wald NJ. Source: Prenatal Diagnosis. 2001 September; 21(9): 737-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559909&dopt=Abstract
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Association between Down syndrome and portohepatic shunt. Author(s): Courtens W, Segers V, Johansson A, Avni FE. Source: American Journal of Medical Genetics. 2000 July 17; 93(2): 166-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10869124&dopt=Abstract
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Association between presenilin-1 polymorphism and maternal meiosis II errors in Down syndrome. Author(s): Petersen MB, Karadima G, Samaritaki M, Avramopoulos D, Vassilopoulos D, Mikkelsen M. Source: American Journal of Medical Genetics. 2000 August 28; 93(5): 366-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951459&dopt=Abstract
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Asynchrony of lexical and morphosyntactic development in children with Down Syndrome. Author(s): Vicari S, Caselli MC, Tonucci F. Source: Neuropsychologia. 2000; 38(5): 634-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10689040&dopt=Abstract
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Attenuated responses to sympathoexcitation in individuals with Down syndrome. Author(s): Fernhall B, Otterstetter M. Source: Journal of Applied Physiology (Bethesda, Md. : 1985). 2003 June; 94(6): 2158-65. Epub 2003 February 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576412&dopt=Abstract
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Atypical attachment in infancy and early childhood among children at developmental risk. III. Maternal sensitivity, child functional level, and attachment in Down syndrome. Author(s): Atkinson L, Chisholm VC, Scott B, Goldberg S, Vaughn BE, Blackwell J, Dickens S, Tam F. Source: Monographs of the Society for Research in Child Development. 1999; 64(3): 4566; Discussion 213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10597542&dopt=Abstract
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Atypical Down syndrome phenotype with severe developmental delay, hypertonia, and seizures in a child with translocation trisomy 21. Author(s): Keppler-Noreuil KM, Welch JL, Major HJ, Qiau Q, Jordan DK, Patil SR. Source: Developmental Medicine and Child Neurology. 2002 January; 44(1): 64-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11811653&dopt=Abstract
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Autistic disorders in Down syndrome: background factors and clinical correlates. Author(s): Rasmussen P, Borjesson O, Wentz E, Gillberg C. Source: Developmental Medicine and Child Neurology. 2001 November; 43(11): 750-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730149&dopt=Abstract
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BAC and PAC contigs covering 3.5 Mb of the Down syndrome congenital heart disease region between D21S55 and MX1 on chromosome 21. Author(s): Hubert RS, Mitchell S, Chen XN, Ekmekji K, Gadomski C, Sun Z, Noya D, Kim UJ, Chen C, Shizuya H, Simon M, de Jong PJ, Korenberg JR. Source: Genomics. 1997 April 15; 41(2): 218-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9143497&dopt=Abstract
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Bacterial contig map of the 21q11 region associated with Alzheimer's disease and abnormal myelopoiesis in Down syndrome. Author(s): Groet J, Ives JH, South AP, Baptista PR, Jones TA, Yaspo ML, Lehrach H, Potier MC, Van Broeckhoven C, Nizetic D. Source: Genome Research. 1998 April; 8(4): 385-98. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9548974&dopt=Abstract
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Basal body temperature curves and endocrine pattern of menstrual cycles in Down syndrome. Author(s): Cento RM, Ragusa L, Proto C, Alberti A, Romano C, Boemi G, Colabucci F, Lanzone A. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1996 April; 10(2): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8701788&dopt=Abstract
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Basal ganglia volume in adults with Down syndrome. Author(s): Aylward EH, Li Q, Habbak QR, Warren A, Pulsifer MB, Barta PE, Jerram M, Pearlson G. Source: Psychiatry Research. 1997 May 16; 74(2): 73-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9204510&dopt=Abstract
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Bedside estimation of Down syndrome risk during first-trimester ultrasound screening. Author(s): Herman A, Dreazen E, Herman AM, Batukan CE, Holzgreve W, Tercanli S. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2002 November; 20(5): 468-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423484&dopt=Abstract
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Behavior problems of children with Down syndrome and life events. Author(s): Coe DA, Matson JL, Russell DW, Slifer KJ, Capone GT, Baglio C, Stallings S. Source: Journal of Autism and Developmental Disorders. 1999 April; 29(2): 149-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10382135&dopt=Abstract
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Behavioral assessment of the Ts65Dn mouse, a model for Down syndrome: altered behavior in the elevated plus maze and open field. Author(s): Coussons-Read ME, Crnic LS. Source: Behavior Genetics. 1996 January; 26(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8852727&dopt=Abstract
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Behavioral capabilities and mortality risk in adults with and without Down syndrome. Author(s): Strauss D, Zigman WB. Source: Am J Ment Retard. 1996 November; 101(3): 269-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8933901&dopt=Abstract
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Behavioral phenotype of individuals with Down syndrome. Author(s): Chapman RS, Hesketh LJ. Source: Mental Retardation and Developmental Disabilities Research Reviews. 2000; 6(2): 84-95. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10899801&dopt=Abstract
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Beta-amyloid deposition and neurofibrillary tangle association with caspase activation in Down syndrome. Author(s): Head E, Lott IT, Cribbs DH, Cotman CW, Rohn TT. Source: Neuroscience Letters. 2002 September 13; 330(1): 99-103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213643&dopt=Abstract
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Beta-Amyloid peptide and amyloid precursor proteins in olfactory mucosa of patients with Alzheimer's disease, Parkinson's disease, and Down syndrome. Author(s): Crino PB, Martin JA, Hill WD, Greenberg B, Lee VM, Trojanowski JQ. Source: The Annals of Otology, Rhinology, and Laryngology. 1995 August; 104(8): 65561. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7639477&dopt=Abstract
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Beta-amyloid precursor protein, ETS-2 and collagen alpha 1 (VI) chain precursor, encoded on chromosome 21, are not overexpressed in fetal Down syndrome: further evidence against gene dosage effect. Author(s): Engidawork E, Baiic N, Fountoulakis M, Dierssen M, Greber-Platzer S, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 335-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771756&dopt=Abstract
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beta-Thalassemia major associated with Down syndrome. Author(s): Keser I, Canatan D, Guzeloglu-Kayisli O, Cosan R, Luleci G. Source: Annales De Genetique. 2001 April-June; 44(2): 57-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11563365&dopt=Abstract
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Between pregnancy biological variability of first trimester markers of Down syndrome and the implications for screening in subsequent pregnancies: an issue revisited. Author(s): Spencer K. Source: Prenatal Diagnosis. 2002 October; 22(10): 874-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378568&dopt=Abstract
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Between pregnancy biological variability of first trimester markers of Down syndrome: implications for screening in subsequent pregnancies. Author(s): Spencer K. Source: Prenatal Diagnosis. 2001 June; 21(6): 445-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11438946&dopt=Abstract
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Between-pregnancy biological variability of maternal serum alpha-fetoprotein and free beta hCG: implications for Down syndrome screening in subsequent pregnancies. Author(s): Spencer K. Source: Prenatal Diagnosis. 1997 January; 17(1): 39-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9021827&dopt=Abstract
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Biochemical screening for Down syndrome in pregnancies following renal transplantation. Author(s): Karidas CN, Michailidis GD, Spencer K, Economides DL. Source: Prenatal Diagnosis. 2002 March; 22(3): 226-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920899&dopt=Abstract
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Biochemical screening for Down syndrome in renal failure. Author(s): Lam CM, Wong SF, Chow KM. Source: American Journal of Obstetrics and Gynecology. 2003 February; 188(2): 597; Author Reply 597. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12592277&dopt=Abstract
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Biochemical screening for Down syndrome. Author(s): Cuckle H. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2000 September; 92(1): 97-101. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10986441&dopt=Abstract
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Biochemical screening for Down syndrome: patients' perception of risk. Author(s): O'Connell MP, Holding S, Morgan RJ, Lindow SW. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2000 March; 68(3): 215-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699191&dopt=Abstract
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Biochemical screening tests for Down syndrome. Author(s): Coetzee E, Viljoen D. Source: South African Medical Journal. Suid-Afrikaanse Tydskrif Vir Geneeskunde. 1995 February; 85(2): 72-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7541163&dopt=Abstract
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Biomarkers of oxidative stress are significantly elevated in Down syndrome. Author(s): Jovanovic SV, Clements D, MacLeod K. Source: Free Radical Biology & Medicine. 1998 December; 25(9): 1044-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9870557&dopt=Abstract
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Biometric measurements of the eyes in teenagers and young adults with Down syndrome. Author(s): Haugen OH, Hovding G, Eide GE. Source: Acta Ophthalmologica Scandinavica. 2001 December; 79(6): 616-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11782229&dopt=Abstract
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Birth prevalence of Down syndrome in Singapore from 1993 to 1998. Author(s): Lai FM, Woo BH, Tan KH, Huang J, Lee ST, Yan TB, Tan BH, Chew SK, Yeo GS. Source: Singapore Med J. 2002 February; 43(2): 070-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11993893&dopt=Abstract
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Bone mineral density and muscle strength in young men with mental retardation (with and without Down syndrome). Author(s): Angelopoulou N, Matziari C, Tsimaras V, Sakadamis A, Souftas V, Mandroukas K. Source: Calcified Tissue International. 2000 March; 66(3): 176-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666490&dopt=Abstract
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Brachycephaly is ineffective for detection of Down syndrome in early midtrimester fetuses. Author(s): Borrell A, Costa D, Martinez JM, Puerto B, Carrio A, Ojuel J, Fortuny A. Source: Early Human Development. 1997 January 3; 47(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9118829&dopt=Abstract
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Brain and eye pathology in an infant with Down syndrome and tuberous sclerosis. Author(s): Jay V. Source: Pediatric Neurology. 1996 July; 15(1): 57-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8858702&dopt=Abstract
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Brain cognition and metabolism in Down syndrome adults in association with development of dementia. Author(s): Dani A, Pietrini P, Furey ML, McIntosh AR, Grady CL, Horwitz B, Freo U, Alexander GE, Schapiro MB. Source: Neuroreport. 1996 November 25; 7(18): 2933-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9116213&dopt=Abstract
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Brain vasopressin levels in Down syndrome and Alzheimer's disease. Author(s): Labudova O, Fang-Kircher S, Cairns N, Moenkemann H, Yeghiazaryan K, Lubec G. Source: Brain Research. 1998 September 21; 806(1): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9739107&dopt=Abstract
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Brief report: affective expression in children with autism or Down syndrome. Author(s): Bieberich AA, Morgan SB. Source: Journal of Autism and Developmental Disorders. 1998 August; 28(4): 333-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9711490&dopt=Abstract
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Brief report: gaze behavior and theory of mind abilities in individuals with autism, down syndrome, and mental retardation of unknown etiology. Author(s): Yirmiya N, Pilowsky T, Solomonica-Levi D, Shulman C. Source: Journal of Autism and Developmental Disorders. 1999 August; 29(4): 333-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10478733&dopt=Abstract
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Brief report: Neuroblastoma in Down syndrome. Author(s): Trebo M, Klaassen R, Weitzman S. Source: Medical and Pediatric Oncology. 1999 August; 33(2): 125. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10398190&dopt=Abstract
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Bucodental health condition in patients with Down syndrome of Cordoba City, Argentina. Author(s): Cornejo LS, Zak GA, Dorronsoro de Cattoni ST, Calamari SE, Azcurra AI, Battellino LJ. Source: Acta Odontol Latinoam. 1996; 9(2): 65-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885251&dopt=Abstract
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Can amnio-polymerase chain reaction alone replace conventional cytogenetic study for women with positive biochemical screening for fetal Down syndrome? Author(s): Leung WC, Lau ET, Lao TT, Tang MH. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 1): 856-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738140&dopt=Abstract
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Can Down syndrome cause persistent non-reactive non-stress test? Author(s): Malhotra B, Deka D. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 March; 72(3): 261-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11226448&dopt=Abstract
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Can we suspect fetal down syndrome by heart evaluation during the second half of pregnancy? Author(s): Respondek-Liberska M, Nowicki G, Krason A, Kaczmarek P, Kociszewska I, Danuta B. Source: Fetal Diagnosis and Therapy. 1999 May-June; 14(3): 143-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364664&dopt=Abstract
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Caring for people with Down syndrome in A&E. Author(s): Houghton BM. Source: Emergency Nurse : the Journal of the Rcn Accident and Emergency Nursing Association. 2001 May; 9(2): 24-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11935619&dopt=Abstract
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Case report: clinical utility of ultrasound nasal bone determination in the prenatal diagnosis of Down syndrome. Author(s): Ferriman E, Cuckle H. Source: Prenatal Diagnosis. 2003 May; 23(5): 433-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749045&dopt=Abstract
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Cases of exceptional language in mental retardation and Down syndrome: explanatory perspectives. Author(s): Rondal JA. Source: Downs Syndr Res Pract. 1998; 5(1): 1-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890855&dopt=Abstract
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Celiac disease and Down syndrome. Author(s): Walker-Smith JA. Source: The Journal of Pediatrics. 2000 December; 137(6): 743-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11113826&dopt=Abstract
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Celiac disease in relation to immunologic serum markers, trace elements, and HLADR and DQ antigens in Swedish children with Down syndrome. Author(s): Hansson T, Anneren G, Sjoberg O, Klareskog L, Dannaeus A. Source: Journal of Pediatric Gastroenterology and Nutrition. 1999 September; 29(3): 28692. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10467993&dopt=Abstract
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Centre-specific ultrasound nuchal translucency medians needed for Down syndrome screening. Author(s): Logghe H, Cuckle H, Sehmi I. Source: Prenatal Diagnosis. 2003 May; 23(5): 389-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749036&dopt=Abstract
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Cerebellar volume in adults with Down syndrome. Author(s): Aylward EH, Habbak R, Warren AC, Pulsifer MB, Barta PE, Jerram M, Pearlson GD. Source: Archives of Neurology. 1997 February; 54(2): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9041863&dopt=Abstract
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Cerebral specialization and verbal-motor integration in adults with and without Down syndrome. Author(s): Welsh TN, Elliott D, Simon DA. Source: Brain and Language. 2003 February; 84(2): 152-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590909&dopt=Abstract
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Cerebral specialization for speech production in persons with Down syndrome. Author(s): Heath M, Elliott D. Source: Brain and Language. 1999 September; 69(2): 193-211. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10447990&dopt=Abstract
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Cervical myelopathy in an adult due to atlantoaxial subluxation associated with Down syndrome: a case study. Author(s): Masuda K, Iwasaki M, Seichi A, Kitagawa T, Nakajima S, Kawaguchi H, Ohnishi I, Nakamura K. Source: Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association. 2003; 8(2): 227-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665962&dopt=Abstract
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c-fos expression in brains of patients with Down syndrome. Author(s): Greber-Platzer S, Balcz B, Cairns N, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 75-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666669&dopt=Abstract
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Changes of periodontal status in patients with Down syndrome during a 7-year period. Author(s): Agholme MB, Dahllof G, Modeer T. Source: European Journal of Oral Sciences. 1999 April; 107(2): 82-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10232455&dopt=Abstract
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Changes of voltage-dependent anion-selective channel proteins VDAC1 and VDAC2 brain levels in patients with Alzheimer's disease and Down syndrome. Author(s): Yoo BC, Fountoulakis M, Cairns N, Lubec G. Source: Electrophoresis. 2001 January; 22(1): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197169&dopt=Abstract
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Characteristic developmental expression of amyloid beta40, 42 and 43 in patients with Down syndrome. Author(s): Hirayama A, Horikoshi Y, Maeda M, Ito M, Takashima S. Source: Brain & Development. 2003 April; 25(3): 180-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12689696&dopt=Abstract
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Characteristic ocular findings in Asian children with Down syndrome. Author(s): Kim JH, Hwang JM, Kim HJ, Yu YS. Source: Eye (London, England). 2002 November; 16(6): 710-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439664&dopt=Abstract
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Characteristics and qualities of the play dates of children with Down syndrome: emerging or true friendships? Author(s): Freeman SF, Kasari C. Source: Am J Ment Retard. 2002 January; 107(1): 16-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11806747&dopt=Abstract
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Characterization of social behaviors and oxytocinergic neurons in the S-100 beta overexpressing mouse model of Down Syndrome. Author(s): Borella A, Sumangali R, Ko J, Whitaker-Azmitia PM. Source: Behavioural Brain Research. 2003 May 15; 141(2): 229-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742260&dopt=Abstract
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Clinical and cardiorespiratory assessment in children with Down syndrome without congenital heart disease. Author(s): Pastore E, Marino B, Calzolari A, Digilio MC, Giannotti A, Turchetta A. Source: Archives of Pediatrics & Adolescent Medicine. 2000 April; 154(4): 408-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10768682&dopt=Abstract
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Clinical and cytogenetic characterisation of a patient with Down syndrome resulting from a 21q22.1-->qter duplication. Author(s): Nadal M, Vigo CG, Melaragno MI, Andrade JA, Alonso LG, Brunoni D, Pritchard M, Estivill X. Source: Journal of Medical Genetics. 2001 January; 38(1): 73-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11334012&dopt=Abstract
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Coeliac disease and Down syndrome: associations not due to genetic linkage on chromosome 21. Author(s): Morris MA, Yiannakou JY, King AL, Brett PM, Biagi F, Vaughan R, Curtis D, Ciclitira PJ. Source: Scandinavian Journal of Gastroenterology. 2000 February; 35(2): 177-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10720116&dopt=Abstract
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Cognitive decline in Down syndrome. Author(s): Margallo-Lana ML, Ballard C, Morris C, Kay D, Tyrer S, Moore B. Source: Archives of Neurology. 2003 July; 60(7): 1024; Author Reply 1024. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873865&dopt=Abstract
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Cognitive decline in Down syndrome: a validity/reliability study of the test for severe impairment. Author(s): Cosgrave MP, McCarron M, Anderson M, Tyrrell J, Gill M, Lawlor BA. Source: Am J Ment Retard. 1998 September; 103(2): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9779286&dopt=Abstract
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Cognitive deterioration in adults with Down syndrome: effects on the individual, caregivers, and service use. Author(s): Oliver C, Crayton L, Holland A, Hall S. Source: Am J Ment Retard. 2000 November; 105(6): 455-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958199&dopt=Abstract
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Cognitive status in Down syndrome individuals with sleep disordered breathing deficits (SDB). Author(s): Andreou G, Galanopoulou C, Gourgoulianis K, Karapetsas A, Molyvdas P. Source: Brain and Cognition. 2002 October; 50(1): 145-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372360&dopt=Abstract
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Collagenoma in Down syndrome. Author(s): Togawa Y, Nohira G, Shinkai H, Utani A. Source: The British Journal of Dermatology. 2003 March; 148(3): 596-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12653762&dopt=Abstract
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Combined first-trimester versus second-trimester serum screening for Down syndrome: a cost analysis. Author(s): Cusick W, Buchanan P, Hallahan TW, Krantz DA, Larsen JW Jr, Macri JN. Source: American Journal of Obstetrics and Gynecology. 2003 March; 188(3): 745-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12634651&dopt=Abstract
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Combined second-trimester biochemical and ultrasound screening for Down syndrome. Author(s): Benn PA, Kaminsky LM, Ying J, Borgida AF, Egan JF. Source: Obstetrics and Gynecology. 2002 December; 100(6): 1168-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12468159&dopt=Abstract
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Combined ultrasound biometry, serum markers and age for Down syndrome risk estimation. Author(s): Bahado-Singh RO, Oz AU, Gomez K, Hunter D, Copel J, Baumgarten A, Mahoney MJ. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2000 March; 15(3): 199-204. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10846774&dopt=Abstract
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Comorbidity of autistic spectrum disorders in children with Down syndrome. Author(s): Kent L, Evans J, Paul M, Sharp M. Source: Developmental Medicine and Child Neurology. 1999 March; 41(3): 153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210247&dopt=Abstract
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Comparative genomic sequence analysis of the human chromosome 21 Down syndrome critical region. Author(s): Toyoda A, Noguchi H, Taylor TD, Ito T, Pletcher MT, Sakaki Y, Reeves RH, Hattori M. Source: Genome Research. 2002 September; 12(9): 1323-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213769&dopt=Abstract
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Comparative survival advantage of males with Down syndrome. Author(s): Glasson EJ, Sullivan SG, Hussain R, Petterson BA, Montgomery PD, Bittles AH. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2003 March-April; 15(2): 192-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12621607&dopt=Abstract
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Comparison of different therapy approaches in children with Down syndrome. Author(s): Uyanik M, Bumin G, Kayihan H. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2003 February; 45(1): 68-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654073&dopt=Abstract
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Comparison of models of maternal age-specific risk for Down syndrome live births. Author(s): Morris JK, Wald NJ, Mutton DE, Alberman E. Source: Prenatal Diagnosis. 2003 March; 23(3): 252-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12627430&dopt=Abstract
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Comparison of urinary hyperglycosylated human chorionic gonadotropin concentration with the serum triple screen for Down syndrome detection in high-risk pregnancies. Author(s): Bahado-Singh RO, Oz U, Shahabi S, Mahoney MJ, Baumgarten A, Cole LA. Source: American Journal of Obstetrics and Gynecology. 2000 November; 183(5): 1114-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084551&dopt=Abstract
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Complement association with neurons and beta-amyloid deposition in the brains of aged individuals with Down Syndrome. Author(s): Head E, Azizeh BY, Lott IT, Tenner AJ, Cotman CW, Cribbs DH. Source: Neurobiology of Disease. 2001 April; 8(2): 252-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300721&dopt=Abstract
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Complete atrioventricular septal defect, Down syndrome, and surgical outcome: risk factors. Author(s): Al-Hay AA, MacNeill SJ, Yacoub M, Shore DF, Shinebourne EA. Source: The Annals of Thoracic Surgery. 2003 February; 75(2): 412-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12607648&dopt=Abstract
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Compromise ultrasound dating policy in maternal serum screening for Down syndrome. Author(s): Rahim RR, Cuckle HS, Sehmi IK, Jones RG. Source: Prenatal Diagnosis. 2002 December; 22(13): 1181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478629&dopt=Abstract
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Compulsive-like behavior in individuals with Down syndrome: its relation to mental age level, adaptive and maladaptive behavior. Author(s): Evans DW, Gray FL. Source: Child Development. 2000 March-April; 71(2): 288-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10834464&dopt=Abstract
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Condensed chromatin surface and NORs surface enhancement in mitogen-stimulated lymphocytes of Down syndrome patients. Author(s): Demirtas H, Imamoglu N, Donmez H, Cucer N, Yilmaz A, Candemir Z. Source: Annales De Genetique. 2001 April-June; 44(2): 77-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522245&dopt=Abstract
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Congenital leukaemia in Down Syndrome--a case report. Author(s): Aier M, Zadeng T, Basu D, Biswal N, Nalini P. Source: Indian J Pathol Microbiol. 2002 July; 45(3): 355-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12785186&dopt=Abstract
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Continuity and change in the social competence of children with autism, Down syndrome, and developmental delays. Author(s): Sigman M, Ruskin E, Arbeile S, Corona R, Dissanayake C, Espinosa M, Kim N, Lopez A, Zierhut C. Source: Monographs of the Society for Research in Child Development. 1999; 64(1): 1114. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10412222&dopt=Abstract
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Co-occurrence of Down syndrome and Treacher-Collins syndrome. Author(s): Sonoda T, Sawada K, Kouno K, Takagi J, Ikeda T, Sameshima H, Ikenoue T. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 August; 44(4): 440-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139573&dopt=Abstract
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Coping with a child with Down syndrome: the experiences of mothers in Hong Kong. Author(s): Lam LW, Mackenzie AE. Source: Qualitative Health Research. 2002 February; 12(2): 223-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11837372&dopt=Abstract
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Coronary cameral fistula occurring in a case of Down syndrome. Author(s): Hunter V, Levin SE, Govendrageloo K. Source: Cardiovasc J S Afr. 2001 June-July; 12(3): 166-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11533739&dopt=Abstract
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Correlation between abnormal cardiac physical examination and echocardiographic findings in neonates with Down syndrome. Author(s): McElhinney DB, Straka M, Goldmuntz E, Zackai EH. Source: American Journal of Medical Genetics. 2002 December 1; 113(3): 238-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439890&dopt=Abstract
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Correlations of glutathione peroxidase activity with memory impairment in adults with Down syndrome. Author(s): Brugge K, Nichols S, Saitoh T, Trauner D. Source: Biological Psychiatry. 1999 December 15; 46(12): 1682-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10624550&dopt=Abstract
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Cortical laminar necrosis in a patient with moyamoya disease associated with Down syndrome: MR imaging findings. Author(s): Takeda K, Takahashi S, Higano S, Kurihara N, Haginoya K, Shirane R, Sakamoto K. Source: Radiat Med. 1997 January-February; 15(1): 59-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9134587&dopt=Abstract
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Cost analysis of Down syndrome screening in advanced maternal age. Author(s): Hartnett J, Borgida AF, Benn PA, Feldman DM, DeRoche ME, Egan JF. Source: J Matern Fetal Neonatal Med. 2003 February;13(2):80-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12735407&dopt=Abstract
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Cost-benefit analysis of prenatal diagnosis for Down syndrome using the British or the American approach. Author(s): Vintzileos AM, Ananth CV, Smulian JC, Day-Salvatore DL, Beazoglou T, Knuppel RA. Source: Obstetrics and Gynecology. 2000 April; 95(4): 577-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10725493&dopt=Abstract
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Cost-benefit analysis of prenatal diagnosis for Down syndrome using the British or the American approach. Author(s): Walker M, Pandya P. Source: Obstetrics and Gynecology. 2000 September; 96(3): 481. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11001699&dopt=Abstract
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Cost-effectiveness of estimating gestational age by ultrasonography in Down syndrome screening. Author(s): Benn PA, Rodis JF, Beazoglou T. Source: Obstetrics and Gynecology. 1999 July; 94(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389713&dopt=Abstract
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Counting and cardinal understanding in children with Down syndrome and typically developing children. Author(s): Nye J, Fluck M, Buckley S. Source: Downs Syndr Res Pract. 2001 October; 7(2): 68-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721532&dopt=Abstract
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Craniofacial maturity and perceived personality in children with Down syndrome. Author(s): Fidler DJ, Hodapp RM. Source: Am J Ment Retard. 1999 September; 104(5): 410-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10541412&dopt=Abstract
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Critical appraisal of the use of nuchal fold thickness measurements for the prediction of Down syndrome. Author(s): Locatelli A, Piccoli MG, Vergani P, Mariani E, Ghidini A, Mariani S, Pezzullo JC. Source: American Journal of Obstetrics and Gynecology. 2000 January; 182(1 Pt 1): 192-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10649178&dopt=Abstract
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Croatian population data for arylsulfatase a pseudodeficiency-associated mutations in healthy subjects, and in patients with Alzheimer-type dementia and Down syndrome. Author(s): Bognar SK, Furac I, Kubat M, Cosovic C, Demarin V. Source: Archives of Medical Research. 2002 September-October; 33(5): 473-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12459318&dopt=Abstract
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Crohn's disease in a child with Down syndrome. Author(s): Yamamoto M, Abo W, Hori T, Nakada T, Tachibana N, Hatada Y, Kaimori M. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2002 October; 44(5): 537-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12225558&dopt=Abstract
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Cryptic duplication of 21q in an individual with a clinical diagnosis of Down syndrome. Author(s): Forster-Gibson CJ, Davies J, MacKenzie JJ, Harrison K. Source: Clinical Genetics. 2001 June; 59(6): 438-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453976&dopt=Abstract
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Cutaneous aspects of Down syndrome. Author(s): Dourmishev A, Miteva L, Mitev V, Pramatarov K, Schwartz RA. Source: Cutis; Cutaneous Medicine for the Practitioner. 2000 December; 66(6): 420-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11138359&dopt=Abstract
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Cut-off criteria for second-trimester nuchal skinfold thickness for prenatal detection of Down syndrome in a Thai population. Author(s): Tannirandorn Y, Manotaya S, Uerpairojkit B, Tanawattanacharoen S, Charoenvidhya D, Phaosavasdi S. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 May; 65(2): 137-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10405057&dopt=Abstract
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Cystathionine-beta-synthase cDNA transfection alters the sensitivity and metabolism of 1-beta-D-arabinofuranosylcytosine in CCRF-CEM leukemia cells in vitro and in vivo: a model of leukemia in Down syndrome. Author(s): Taub JW, Huang X, Ge Y, Dutcher JA, Stout ML, Mohammad RM, Ravindranath Y, Matherly LH. Source: Cancer Research. 2000 November 15; 60(22): 6421-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11103808&dopt=Abstract
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Cytogenetic and molecular study of 32 Down syndrome families: potential leukaemia predisposing role of the most proximal segment of chromosome 21q. Author(s): Cavani S, Perfumo C, Argusti A, Pierluigi M, Perroni L, Schmiegelow K, Petersen MB, Cotter FE, Strigini P, Dagna-Bricarelli F, Nizetic D. Source: British Journal of Haematology. 1998 October; 103(1): 213-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9792310&dopt=Abstract
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Cytogenetic studies of 1001 Down syndrome cases from Andhra Pradesh, India. Author(s): Jyothy A, Kumar KS, Rao GN, Rao VB, Swarna M, Devi BU, Sujatha M, Kumari CK, Reddy PP. Source: The Indian Journal of Medical Research. 2000 April; 111: 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10935320&dopt=Abstract
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Cytomegalovirus infection in children with Down syndrome in a day-care center in Brazil. Author(s): do Canto CL, Granato CF, Garcez E, Villas Boas LS, Fink MC, Estevam MP, Pannuti CS. Source: Revista Do Instituto De Medicina Tropical De Sao Paulo. 2000 July-August; 42(4): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10968879&dopt=Abstract
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Decreased alpha-endosulfine, an endogenous regulator of ATP-sensitive potassium channels, in brains from adult Down syndrome patients. Author(s): Kim SH, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771735&dopt=Abstract
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Decreased brain histamine-releasing factor protein in patients with Down syndrome and Alzheimer's disease. Author(s): Kim SH, Cairns N, Fountoulakisc M, Lubec G. Source: Neuroscience Letters. 2001 March 2; 300(1): 41-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172935&dopt=Abstract
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Decreased brain levels of 2',3'-cyclic nucleotide-3'-phosphodiesterase in Down syndrome and Alzheimer's disease. Author(s): Vlkolinsky R, Cairns N, Fountoulakis M, Lubec G. Source: Neurobiology of Aging. 2001 July-August; 22(4): 547-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11445254&dopt=Abstract
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Decreased central corneal thickness in children with Down syndrome. Author(s): Evereklioglu C, Yilmaz K, Bekir NA. Source: Journal of Pediatric Ophthalmology and Strabismus. 2002 September-October; 39(5): 274-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12353899&dopt=Abstract
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Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer's disease and Down syndrome. Author(s): Kim SH, Vlkolinsky R, Cairns N, Lubec G. Source: Cellular and Molecular Life Sciences : Cmls. 2000 November; 57(12): 1810-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130185&dopt=Abstract
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Decreased protein levels of complex I 30-kDa subunit in fetal Down syndrome brains. Author(s): Kim SH, Fountoulakis M, Dierssen M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 109-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771736&dopt=Abstract
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Deficiency of the vestibular spine in atrioventricular septal defects in human fetuses with down syndrome. Author(s): Blom NA, Ottenkamp J, Wenink AG, Gittenberger-de Groot AC. Source: The American Journal of Cardiology. 2003 January 15; 91(2): 180-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12521631&dopt=Abstract
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Deficient brain snRNP70K in patients with Down syndrome. Author(s): Seidl R, Labudova O, Krapfenbauer K, Henriksson EW, Craft J, TurhaniSchatzmann D, Achsel T, Bidmon B, Pruijn GJ, Cairns N, Lubec G. Source: Electrophoresis. 2001 January; 22(1): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11197177&dopt=Abstract
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Delay of gratification in young adults with Down syndrome. Author(s): Cuskelly M, Einam M, Jobling A. Source: Downs Syndr Res Pract. 2001 October; 7(2): 60-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721531&dopt=Abstract
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Dental care access among individuals with Down syndrome in France. Author(s): Allison PJ, Hennequin M, Faulks D. Source: Spec Care Dentist. 2000 January-February; 20(1): 28-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11203873&dopt=Abstract
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Depression and dementia in aging adults with Down syndrome: a case study approach. Author(s): Sung H, Hawkins BA, Eklund SJ, Kim KA, Foose A, May ME, Rogers NB. Source: Mental Retardation. 1997 February; 35(1): 27-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9046784&dopt=Abstract
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Descriptive information about Down syndrome: a content analysis of serum screening leaflets. Author(s): Bryant LD, Murray J, Green JM, Hewison J, Sehmi I, Ellis A. Source: Prenatal Diagnosis. 2001 December; 21(12): 1057-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746164&dopt=Abstract
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Detection and false-positive rates of maternal serum markers for Down syndrome screening according to maternal age in women over 35 years of age. A study of the agreement of eight dedicated software packages. Author(s): Muller F, Thalabard JC, Ngo S, Dommergues M. Source: Prenatal Diagnosis. 2002 May; 22(5): 350-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001184&dopt=Abstract
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Detection of maternal serum hCG glycoform variants in the second trimester of pregnancies affected by Down syndrome using a lectin immunoassay. Author(s): Talbot JA, Spencer K, Abushoufa RA. Source: Prenatal Diagnosis. 2003 January; 23(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12533803&dopt=Abstract
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Determinants of parental decisions after the prenatal diagnosis of down syndrome: bringing in context. Author(s): Britt DW, Risinger ST, Miller V, Mans MK, Krivchenia EL, Evans MI. Source: American Journal of Medical Genetics. 2000 August 28; 93(5): 410-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951466&dopt=Abstract
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Development of refractive error and strabismus in children with Down syndrome. Author(s): Cregg M, Woodhouse JM, Stewart RE, Pakeman VH, Bromham NR, Gunter HL, Trojanowska L, Parker M, Fraser WI. Source: Investigative Ophthalmology & Visual Science. 2003 March; 44(3): 1023-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601024&dopt=Abstract
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Developmental disabilities and understanding the needs of patients with mental retardation and Down syndrome. Author(s): Surabian SR. Source: J Calif Dent Assoc. 2001 June; 29(6): 415-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11484297&dopt=Abstract
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Developmental instability of the cerebellum and its relevance to Down syndrome. Author(s): Shapiro BL. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 11-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771737&dopt=Abstract
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Diagnosis and therapy for airway obstruction in children with Down syndrome. Author(s): Mitchell RB, Call E, Kelly J. Source: Archives of Otolaryngology--Head & Neck Surgery. 2003 June; 129(6): 642-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12810469&dopt=Abstract
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Diagnosis of fetal acrania during the first trimester nuchal translucency screening for Down syndrome. Author(s): Cheng CC, Lee FK, Lin HW, Shih JC, Tsai MS. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 February; 80(2): 139-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566186&dopt=Abstract
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Diagnostic performance of intracardiac echogenic foci for Down syndrome: a metaanalysis. Author(s): Sotiriadis A, Makrydimas G, Ioannidis JP. Source: Obstetrics and Gynecology. 2003 May; 101(5 Pt 1): 1009-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12738165&dopt=Abstract
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Differences between GABA levels in Alzheimer's disease and Down syndrome with Alzheimer-like neuropathology. Author(s): Seidl R, Cairns N, Singewald N, Kaehler ST, Lubec G. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2001 February; 363(2): 13945. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218066&dopt=Abstract
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Differences in cardiovascular disease risk between nondiabetic adults with mental retardation with and without Down syndrome. Author(s): Draheim CC, McCubbin JA, Williams DP. Source: Am J Ment Retard. 2002 May; 107(3): 201-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966333&dopt=Abstract
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Differential display reveals downregulation of the phospholipid transfer protein (PLTP) at the mRNA level in brains of patients with Down syndrome. Author(s): Krapfenbauer K, Yoo BC, Kim SH, Cairns N, Lubec G. Source: Life Sciences. 2001 March 23; 68(18): 2169-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11324722&dopt=Abstract
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Differential expression of molecular chaperones in brain of patients with Down syndrome. Author(s): Yoo BC, Vlkolinsky R, Engidawork E, Cairns N, Fountoulakis M, Lubec G. Source: Electrophoresis. 2001 April; 22(6): 1233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358150&dopt=Abstract
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Differential gene expression studies to explore the molecular pathophysiology of Down syndrome. Author(s): Antonarakis SE, Lyle R, Chrast R, Scott HS. Source: Brain Research. Brain Research Reviews. 2001 October; 36(2-3): 265-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11690624&dopt=Abstract
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Diffuse hepatic fibrosis with transient myeloproliferative disorders in Down syndrome. Author(s): Hongeng S, Pakakasama S, Hathirat P, Phuapradid P, Worapongpaiboon S. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2000 November-December; 22(6): 543-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11132225&dopt=Abstract
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Distinctive multidrug sensitivity and outcome of acute erythroblastic and megakaryoblastic leukemia in children with Down syndrome. Author(s): Yamada S, Hongo T, Okada S, Watanabe C, Fujii Y, Hori H, Yazaki M, Hanada R, Horikoshi Y. Source: International Journal of Hematology. 2001 December; 74(4): 428-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11794699&dopt=Abstract
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Do children with Down syndrome have difficulty with argument structure? Author(s): Grela BG. Source: Journal of Communication Disorders. 2003 July-August; 36(4): 263-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837586&dopt=Abstract
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Does a 'notched' nuchal translucency indicate Down syndrome fetuses or other adverse pregnancy outcome? Author(s): Maymon R, Dreazen E, Buckovsky I, Weinraub Z, Herman A. Source: Prenatal Diagnosis. 2001 May; 21(5): 403-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11360284&dopt=Abstract
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Donepezil for the treatment of language deficits in adults with Down syndrome: a preliminary 24-week open trial. Author(s): Heller JH, Spiridigliozzi GA, Sullivan JA, Doraiswamy PM, Krishnan RR, Kishnani PS. Source: American Journal of Medical Genetics. 2003 January 15; 116A(2): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494428&dopt=Abstract
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Donepezil use in the treatment of dementia associated with Down syndrome. Author(s): Cipriani G, Bianchetti A, Trabucchi M. Source: Archives of Neurology. 2003 February; 60(2): 292; Author Reply 292. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580720&dopt=Abstract
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Double-positive maternal serum screening results for down syndrome and open neural tube defects: An indicator for fetal structural or chromosomal abnormalities and adverse obstetric outcomes. Author(s): Chitayat D, Farrell SA, Huang T, Meier C, Wyatt PR, Summers AM. Source: American Journal of Obstetrics and Gynecology. 2002 September; 187(3): 758-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12237660&dopt=Abstract
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Down syndrome and Alzheimer's disease: a link between development and aging. Author(s): Lott IT, Head E. Source: Mental Retardation and Developmental Disabilities Research Reviews. 2001; 7(3): 172-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11553933&dopt=Abstract
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Down syndrome and cell-free fetal DNA in archived maternal serum. Author(s): Lee T, LeShane ES, Messerlian GM, Canick JA, Farina A, Heber WW, Bianchi DW. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 121721. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439507&dopt=Abstract
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Down syndrome and Crohn's disease: an extremely rare association. Author(s): Persic M, Dessardo S, Subat-Dezulovic M, Ahel V, Rozmanic V. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 October; 43(5): 519-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737719&dopt=Abstract
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Down syndrome and folic acid update. Author(s): Hine RJ, James SJ. Source: Journal of the American Dietetic Association. 2000 September; 100(9): 1004. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11019341&dopt=Abstract
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Down syndrome and the phonological loop: the evidence for, and importance of, a specific verbal short-term memory deficit. Author(s): Jarrold C, Baddeley AD, Phillips C. Source: Downs Syndr Res Pract. 1999 September; 6(2): 61-75. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11276981&dopt=Abstract
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Down syndrome before Down: a postscript. Author(s): Berg JM. Source: American Journal of Medical Genetics. 2003 January 1; 116A(1): 97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12476461&dopt=Abstract
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Down syndrome before Down: a retrospect. Author(s): Berg JM, Korossy M. Source: American Journal of Medical Genetics. 2001 August 1; 102(2): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477617&dopt=Abstract
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Down syndrome cell adhesion molecule is conserved in mouse and highly expressed in the adult mouse brain. Author(s): Barlow GM, Micales B, Lyons GE, Korenberg JR. Source: Cytogenetics and Cell Genetics. 2001; 94(3-4): 155-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11856873&dopt=Abstract
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Down syndrome clinic in a semi-rural setting. Author(s): Lovell CM, Saul RA. Source: American Journal of Medical Genetics. 1999 June 25; 89(2): 91-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559763&dopt=Abstract
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Down syndrome congenital heart disease: a narrowed region and a candidate gene. Author(s): Barlow GM, Chen XN, Shi ZY, Lyons GE, Kurnit DM, Celle L, Spinner NB, Zackai E, Pettenati MJ, Van Riper AJ, Vekemans MJ, Mjaatvedt CH, Korenberg JR. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2001 March-April; 3(2): 91-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11280955&dopt=Abstract
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Down syndrome fetal loss rate in early pregnancy. Author(s): Morris J, Wald N. Source: Prenatal Diagnosis. 2000 August; 20(8): 685-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951486&dopt=Abstract
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Down syndrome in Israel. Author(s): Merrick J. Source: Downs Syndr Res Pract. 2001 July; 6(3): 128-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501215&dopt=Abstract
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Down syndrome livebirth rate in the eastern part of Switzerland between 1980 and 1996 stays constant in spite of growing numbers of prenatally diagnosed and subsequently terminated cases. Author(s): Mutter M, Binkert F, Schinzel A. Source: Prenatal Diagnosis. 2002 September; 22(9): 835-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224083&dopt=Abstract
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Down syndrome maternal serum marker screening after 18 weeks' gestation. Author(s): Muller F, Dreux S, Oury JF, Luton D, Uzan S, Uzan M, Levardon M, Dommergues M. Source: Prenatal Diagnosis. 2002 November; 22(11): 1001-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424764&dopt=Abstract
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Down syndrome phonology: developmental patterns and intervention strategies. Author(s): Stoel-Gammon C. Source: Downs Syndr Res Pract. 2001 October; 7(3): 93-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721538&dopt=Abstract
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Down syndrome risk estimation after normal genetic sonography. Author(s): Vintzileos AM, Guzman ER, Smulian JC, Yeo L, Scorza WE, Knuppel RA. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 1226-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439509&dopt=Abstract
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Down syndrome with transient myeloid leukemia and urological abnormality. Author(s): Shah AA, Mehta AA, Desai M, Shah AV. Source: Indian Pediatrics. 2003 February; 40(2): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626832&dopt=Abstract
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Down syndrome: a study of chromosomal mosaicism. Author(s): Modi D, Berde P, Bhartiya D. Source: Reproductive Biomedicine Online. 2003 June; 6(4): 499-503. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831601&dopt=Abstract
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Down syndrome: advances in molecular biology and the neurosciences. Author(s): Capone GT. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 2001 February; 22(1): 40-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11265922&dopt=Abstract
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Down syndrome: identification and surgical management of obstructive sleep apnea. Author(s): Lefaivre JF, Cohen SR, Burstein FD, Simms C, Scott PH, Montgomery GL, Graham L, Kattos AV. Source: Plastic and Reconstructive Surgery. 1997 March; 99(3): 629-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9047180&dopt=Abstract
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Down syndrome: perinatal complications and counseling experiences in 216 patients. Author(s): Spahis JK, Wilson GN. Source: American Journal of Medical Genetics. 1999 June 25; 89(2): 96-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559764&dopt=Abstract
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Down syndrome: possible predisposition to retinoblastoma. Author(s): Brichard B, Vermylen C, De Potter P, Casteels I. Source: Medical and Pediatric Oncology. 2003 July; 41(1): 73-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764751&dopt=Abstract
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Down syndrome: prenatal risk assessment and diagnosis. Author(s): Newberger DS. Source: American Family Physician. 2000 August 15; 62(4): 825-32, 837-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969860&dopt=Abstract
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Down syndrome: progress in research. Author(s): Roizen NJ. Source: Mental Retardation and Developmental Disabilities Research Reviews. 2001; 7(1): 38-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241881&dopt=Abstract
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Down syndrome: still a social stigma. Author(s): Jain R, Thomasma DC, Ragas R. Source: American Journal of Perinatology. 2002 February; 19(2): 99-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11938484&dopt=Abstract
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Drebrin, a dendritic spine protein, is manifold decreased in brains of patients with Alzheimer's disease and Down syndrome. Author(s): Shim KS, Lubec G. Source: Neuroscience Letters. 2002 May 24; 324(3): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12009525&dopt=Abstract
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Ear, nose and throat disorders in children with Down syndrome. Author(s): Akyol MU. Source: The Laryngoscope. 2003 June; 113(6): 1089-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12782832&dopt=Abstract
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Ear, nose and throat disorders in children with Down syndrome. Author(s): Mitchell RB, Call E, Kelly J. Source: The Laryngoscope. 2003 February; 113(2): 259-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12567079&dopt=Abstract
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Earlier onset of Alzheimer's disease in men with Down syndrome. Author(s): Schupf N, Kapell D, Nightingale B, Rodriguez A, Tycko B, Mayeux R. Source: Neurology. 1998 April; 50(4): 991-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9566384&dopt=Abstract
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Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: a regional quantitative analysis. Author(s): Leverenz JB, Raskind MA. Source: Experimental Neurology. 1998 April; 150(2): 296-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9527899&dopt=Abstract
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Early conjectures that Down syndrome is caused by chromosomal nondisjunction. Author(s): Carter KC. Source: Bulletin of the History of Medicine. 2002 Fall; 76(3): 528-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12486916&dopt=Abstract
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Early genetic sonogram for Down syndrome detection. Author(s): Bahado-Singh RO, Mendilcioglu I, Rowther M, Choi SJ, Oz U, Yousefi NF, Mahoney MJ. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 1235-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439511&dopt=Abstract
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Early menarche in Japanese Down syndrome. Author(s): Takano T, Takaki H, Kawano H, Nonaka K. Source: Pediatrics. 1999 April; 103(4 Pt 1): 854-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10206857&dopt=Abstract
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Early transvaginal measurement of cephalic index for the detection of down syndrome fetuses. Author(s): Rosati P, Guariglia L. Source: Fetal Diagnosis and Therapy. 1999 January-February; 14(1): 38-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10072649&dopt=Abstract
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Early transvaginal measurement of transcerebellar diameter in Down syndrome. Author(s): Guariglia L, Rosati P. Source: Fetal Diagnosis and Therapy. 1998 September-October; 13(5): 287-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9813421&dopt=Abstract
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Early-onset Moyamoya syndrome in a patient with Down syndrome: case report and review of the literature. Author(s): Dai AI, Shaikh ZA, Cohen ME. Source: Journal of Child Neurology. 2000 October; 15(10): 696-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063086&dopt=Abstract
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Eating habits of young children with Down syndrome in The Netherlands: adequate nutrient intakes but delayed introduction of solid food. Author(s): Hopman E, Csizmadia CG, Bastiani WF, Engels QM, de Graaf EA, le Cessie S, Mearin ML. Source: Journal of the American Dietetic Association. 1998 July; 98(7): 790-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9664921&dopt=Abstract
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Echocardiographic evaluation of left ventricular systolic function in the Down syndrome. Author(s): Russo MG, Pacileo G, Marino B, Pisacane C, Calabro P, Ammirati A, Calabro R. Source: The American Journal of Cardiology. 1998 May 15; 81(10): 1215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9604950&dopt=Abstract
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Effect of Down syndrome on the dimensions of dental crowns and tissues. Author(s): Bell E, Townsend G, Wilson D, Kieser J, Hughes T. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 September-October; 13(5): 690-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11505477&dopt=Abstract
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Effect of fetal gender on first trimester markers and on Down syndrome screening. Author(s): Yaron Y, Wolman I, Kupferminc MJ, Ochshorn Y, Many A, Orr-Urtreger A. Source: Prenatal Diagnosis. 2001 December; 21(12): 1027-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11746159&dopt=Abstract
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Effect of maternal smoking and coffee consumption on the risk of having a recognized Down syndrome pregnancy. Author(s): Torfs CP, Christianson RE. Source: American Journal of Epidemiology. 2000 December 15; 152(12): 1185-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130625&dopt=Abstract
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Effect of menopause on cognitive performance in women with Down syndrome. Author(s): Patel BN, Seltzer GB, Wu HS, Schupf N. Source: Neuroreport. 2001 August 28; 12(12): 2659-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522943&dopt=Abstract
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Effect of study design on the association between nuchal translucency measurement and Down syndrome. Author(s): Mol BW, Lijmer JG, van der Meulen J, Pajkrt E, Bilardo CM, Bossuyt PM. Source: Obstetrics and Gynecology. 1999 November; 94(5 Pt 2): 864-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10546775&dopt=Abstract
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Effects of a treadmill walking program on muscle strength and balance in elderly people with Down syndrome. Author(s): Carmeli E, Kessel S, Coleman R, Ayalon M. Source: The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 2002 February; 57(2): M106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11818429&dopt=Abstract
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Effects of an aerobic rowing training regimen in young adults with Down syndrome. Author(s): Varela AM, Sardinha LB, Pitetti KH. Source: Am J Ment Retard. 2001 March; 106(2): 135-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11321604&dopt=Abstract
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Effects of maintaining and redirecting infant attention on the production of referential communication in infants with and without Down syndrome. Author(s): Legerstee M, Varghese J, van Beek Y. Source: Journal of Child Language. 2002 February; 29(1): 23-48. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11968884&dopt=Abstract
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Efficacy of screening for fetal Down syndrome in the United States from 1974 to 1997. Author(s): Egan JF, Benn P, Borgida AF, Rodis JF, Campbell WA, Vintzileos AM. Source: Obstetrics and Gynecology. 2000 December; 96(6): 979-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11084189&dopt=Abstract
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Elevated expression of beta-site amyloid precursor protein cleaving enzyme 2 in brains of patients with Down syndrome. Author(s): Motonaga K, Itoh M, Becker LE, Goto Y, Takashima S. Source: Neuroscience Letters. 2002 June 21; 326(1): 64-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12052539&dopt=Abstract
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Elevated maternal age-specific rates of Down syndrome liveborn offspring of women of Mexican and Central American origin in California. Author(s): Hook EB, Carothers AD, Hecht CA. Source: Prenatal Diagnosis. 1999 March; 19(3): 245-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210123&dopt=Abstract
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Elevated plasma amyloid beta-peptide 1-42 and onset of dementia in adults with Down syndrome. Author(s): Schupf N, Patel B, Silverman W, Zigman WB, Zhong N, Tycko B, Mehta PD, Mayeux R. Source: Neuroscience Letters. 2001 April 6; 301(3): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11257432&dopt=Abstract
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Elevated second-trimester maternal serum inhibin A levels in Asian pregnancies with fetal down syndrome and other chromosomal abnormalities. Author(s): Hsu JJ, Chiang CH, Hsieh CC, Hsieh TT. Source: Fetal Diagnosis and Therapy. 2003 March-April; 18(2): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12576745&dopt=Abstract
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Emotion recognition by children with Down syndrome. Author(s): Kasari C, Freeman SF, Hughes MA. Source: Am J Ment Retard. 2001 January; 106(1): 59-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11246714&dopt=Abstract
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Empathy and response to distress in children with Down syndrome. Author(s): Kasari C, Freeman SF, Bass W. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2003 March; 44(3): 424-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635971&dopt=Abstract
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Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. Author(s): Cataldo AM, Peterhoff CM, Troncoso JC, Gomez-Isla T, Hyman BT, Nixon RA. Source: American Journal of Pathology. 2000 July; 157(1): 277-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10880397&dopt=Abstract
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Endogenous hydrogen sulfide overproduction in Down syndrome. Author(s): Kamoun P, Belardinelli MC, Chabli A, Lallouchi K, Chadefaux-Vekemans B. Source: American Journal of Medical Genetics. 2003 January 30; 116A(3): 310-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503113&dopt=Abstract
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Energy expenditure in neonates with Down syndrome. Author(s): Bauer J, Teufel U, Doege C, Hans-Juergen G, Beedgen B, Linderkamp O. Source: The Journal of Pediatrics. 2003 August; 143(2): 264-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12970644&dopt=Abstract
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Enhanced levels of prostaglandin E2, leukotriene B4, and matrix metalloproteinase-9 in gingival crevicular fluid from patients with Down syndrome. Author(s): Tsilingaridis G, Yucel-Lindberg T, Modeer T. Source: Acta Odontologica Scandinavica. 2003 June; 61(3): 154-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868689&dopt=Abstract
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Enhancement of lipopolysaccharide-stimulated cyclooxygenase-2 mRNA expression and prostaglandin E2 production in gingival fibroblasts from individuals with Down syndrome. Author(s): Otsuka Y, Ito M, Yamaguchi M, Saito S, Uesu K, Kasai K, Abiko Y, Mega J. Source: Mechanisms of Ageing and Development. 2002 March 31; 123(6): 663-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11850029&dopt=Abstract
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Enhancement of plasminogen activator activity stimulated by LPS in gingival fibroblasts of individuals with Down syndrome. Author(s): Otsuka Y, Ito M, Yamaguchi M, Uesu K, Uehara S, Kasai K, Abiko Y, Mega J. Source: J Oral Sci. 2001 September; 43(3): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11732741&dopt=Abstract
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Epidemiologic study of Down syndrome in a racially diverse California population, 1989-1991. Author(s): Bishop J, Huether CA, Torfs C, Lorey F, Deddens J. Source: American Journal of Epidemiology. 1997 January 15; 145(2): 134-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9006310&dopt=Abstract
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Epidemiology of Down syndrome (Trisomy 21), Hawaii, 1986-97. Author(s): Forrester MB, Merz RD. Source: Teratology. 2002 May; 65(5): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967919&dopt=Abstract
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Estimates for the sensitivity and false-positive rates for second trimester serum screening for Down syndrome and trisomy 18 with adjustment for crossidentification and double-positive results. Author(s): Benn PA, Ying J, Beazoglou T, Egan JF. Source: Prenatal Diagnosis. 2001 January; 21(1): 46-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180240&dopt=Abstract
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Estimating the spontaneous loss of Down syndrome fetuses between the times of chorionic villus sampling, amniocentesis and livebirth. Author(s): Bray IC, Wright DE. Source: Prenatal Diagnosis. 1998 October; 18(10): 1045-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9826896&dopt=Abstract
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Estimation of risk in second trimester serum screening for Down syndrome among women who have already had first trimester screening. Author(s): Hackshaw A, Wald N. Source: Prenatal Diagnosis. 2002 November; 22(11): 1051-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424775&dopt=Abstract
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Ethnic differences in the impact of advanced maternal age on birth prevalence of Down syndrome. Author(s): Khoshnood B, Pryde P, Wall S, Singh J, Mittendorf R, Lee KS. Source: American Journal of Public Health. 2000 November; 90(11): 1778-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11076250&dopt=Abstract
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ETS2 overexpression in transgenic models and in Down syndrome predisposes to apoptosis via the p53 pathway. Author(s): Wolvetang EJ, Wilson TJ, Sanij E, Busciglio J, Hatzistavrou T, Seth A, Hertzog PJ, Kola I. Source: Human Molecular Genetics. 2003 February 1; 12(3): 247-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12554679&dopt=Abstract
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Evaluating motor function in children with Down syndrome: validity of the GMFM. Author(s): Russell D, Palisano R, Walter S, Rosenbaum P, Gemus M, Gowland C, Galuppi B, Lane M. Source: Developmental Medicine and Child Neurology. 1998 October; 40(10): 693-701. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9851239&dopt=Abstract
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Evaluation of cell-free fetal DNA as a second-trimester maternal serum marker of Down syndrome pregnancy. Author(s): Farina A, LeShane ES, Lambert-Messerlian GM, Canick JA, Lee T, Neveux LM, Palomaki GE, Bianchi DW. Source: Clinical Chemistry. 2003 February; 49(2): 239-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560345&dopt=Abstract
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Evaluation of coeliac disease serological markers in Down syndrome patients. Author(s): Rumbo M, Chirdo FG, Ben R, Saldungaray I, Villalobos R. Source: Dig Liver Dis. 2002 February; 34(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926554&dopt=Abstract
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Evaluation of fetal femur length to detect Down syndrome in a Thai population. Author(s): Tannirandorn Y, Manotaya S, Uerpairojkit B, Tanawattanacharoen S, Wacharaprechanont T, Charoenvidhya D. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 May; 73(2): 117-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336730&dopt=Abstract
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Evaluation of the Abbott system in maternal serum screening for Down syndrome: the AxSym analyzer, AFP and hCG reagents and Maciel Prenatal Interpretive Software. Author(s): Muller F, Ngo S, Aegerter P, Le Bourdelles S, Taguel V, Rebiffe M, Faina S, Giraudet P. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1998 September 14; 277(1): 65-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9776046&dopt=Abstract
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Event-related brain potentials during an extended visual recognition memory task depict delayed development of cerebral inhibitory processes among 6-month-old infants with Down syndrome. Author(s): Karrer JH, Karrer R, Bloom D, Chaney L, Davis R. Source: International Journal of Psychophysiology : Official Journal of the International Organization of Psychophysiology. 1998 July; 29(2): 167-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9664227&dopt=Abstract
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Evidence against increased oxidative DNA-damage in Down syndrome. Author(s): Seidl R, Greber S, Schuller E, Bernert G, Cairns N, Lubec G. Source: Neuroscience Letters. 1997 October 17; 235(3): 137-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9406888&dopt=Abstract
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Evidence for apoptosis in the fetal Down syndrome brain. Author(s): Seidl R, Bidmon B, Bajo M, Yoo PC, Cairns N, LaCasse EC, Lubec G. Source: Journal of Child Neurology. 2001 June; 16(6): 438-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417611&dopt=Abstract
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Evidence for increased mitochondrial superoxide production in Down syndrome. Author(s): Capone G, Kim P, Jovanovich S, Payne L, Freund L, Welch K, Miller E, Trush M. Source: Life Sciences. 2002 May 3; 70(24): 2885-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12269400&dopt=Abstract
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Evidence for the relation of herpes simplex virus type 1 to Down syndrome and Alzheimer's disease. Author(s): Cheon MS, Bajo M, Gulesserian T, Cairns N, Lubec G. Source: Electrophoresis. 2001 February; 22(3): 445-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11258753&dopt=Abstract
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Excessive expression of synaptojanin in brains with Down syndrome. Author(s): Arai Y, Ijuin T, Takenawa T, Becker LE, Takashima S. Source: Brain & Development. 2002 March; 24(2): 67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11891094&dopt=Abstract
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Excitatory amino acids and monoamines in parahippocampal gyrus and frontal cortical pole of adults with Down syndrome. Author(s): Risser D, Lubec G, Cairns N, Herrera-Marschitz M. Source: Life Sciences. 1997; 60(15): 1231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9096240&dopt=Abstract
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Expected, prenatally discovered, and born cases of Down syndrome in Denmark during the period 1980-1998. Author(s): Larsen SO, Hansen J, Pedersen BN. Source: Prenatal Diagnosis. 2001 August; 21(8): 630-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11536260&dopt=Abstract
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Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. Author(s): Taub JW, Huang X, Matherly LH, Stout ML, Buck SA, Massey GV, Becton DL, Chang MN, Weinstein HJ, Ravindranath Y. Source: Blood. 1999 August 15; 94(4): 1393-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10438727&dopt=Abstract
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Expression of DNA excision-repair-cross-complementing proteins p80 and p89 in brain of patients with Down Syndrome and Alzheimer's disease. Author(s): Hermon M, Cairns N, Egly JM, Fery A, Labudova O, Lubec G. Source: Neuroscience Letters. 1998 July 17; 251(1): 45-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9714461&dopt=Abstract
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Expression of the dihydropyrimidinase related protein 2 (DRP-2) in Down syndrome and Alzheimer's disease brain is downregulated at the mRNA and dysregulated at the protein level. Author(s): Lubec G, Nonaka M, Krapfenbauer K, Gratzer M, Cairns N, Fountoulakis M. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 161-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666674&dopt=Abstract
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Expression of the mitochondrial ATPase6 gene and Tfam in Down syndrome. Author(s): Lee SH, Lee S, Jun HS, Jeong HJ, Cha WT, Cho YS, Kim JH, Ku SY, Cha KY. Source: Molecules and Cells. 2003 April 30; 15(2): 181-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803480&dopt=Abstract
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Expression of the transcription factor ETS2 in brain of patients with Down syndrome-evidence against the overexpression-gene dosage hypothesis. Author(s): Greber-Platzer S, Schatzmann-Turhani D, Cairns N, Balcz B, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 269-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666682&dopt=Abstract
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Expression patterns and subcellular localization of the Down syndrome candidate protein MNB/DYRK1A suggest a role in late neuronal differentiation. Author(s): Hammerle B, Carnicero A, Elizalde C, Ceron J, Martinez S, Tejedor FJ. Source: The European Journal of Neuroscience. 2003 June; 17(11): 2277-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12814361&dopt=Abstract
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Expressive vocabulary ability of toddlers with Williams syndrome or Down syndrome: a comparison. Author(s): Mervis CB, Robinson BF. Source: Developmental Neuropsychology. 2000; 17(1): 111-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10916578&dopt=Abstract
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Familial Down syndrome: evidence supporting cytoplasmic inheritance. Author(s): Arbuzova S, Cuckle H, Mueller R, Sehmi I. Source: Clinical Genetics. 2001 December; 60(6): 456-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11846739&dopt=Abstract
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Familial MCA/MR syndrome due to inherited submicroscopic translocation t(18;21)(q22.1q21.3) with breakpoint at the Down syndrome critical region. Author(s): Horn D, Neitzel H, Tonnies H, Kalscheuer V, Kunze J, Hinkel GK, Bartsch O. Source: American Journal of Medical Genetics. 2003 March 15; 117A(3): 236-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12599186&dopt=Abstract
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Family influences on adaptive development in young children with Down syndrome. Author(s): Hauser-Cram P, Warfield ME, Shonkoff JP, Krauss MW, Upshur CC, Sayer A. Source: Child Development. 1999 July-August; 70(4): 979-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10446730&dopt=Abstract
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Femoral anteversion osteotomy for the treatment of hip dislocation in Down syndrome: long-term evolution. Author(s): Beguiristain JL, Barriga A, Gent RA. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2001 April; 10(2): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11360785&dopt=Abstract
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Femur/foot length ratio for detection of Down syndrome: results of a multicenter prospective study. The Association Francaise pour le Depistage et la Prevention des Handicaps de l'Enfant Study Group. Author(s): Grandjean H, Sarramon MF. Source: American Journal of Obstetrics and Gynecology. 1995 July; 173(1): 16-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7631674&dopt=Abstract
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Fetal breasts in normal and Down syndrome fetuses. Author(s): Petrikovsky BM, Schneider EP, Klein VR, Wyse LJ, Lesser M. Source: Journal of Clinical Ultrasound : Jcu. 1996 November-December; 24(9): 507-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8906482&dopt=Abstract
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Fetal cells in maternal blood as a second non-invasive step for fetal Down syndrome screening. Author(s): Farina A, Bianchi DW. Source: Prenatal Diagnosis. 1998 September; 18(9): 983-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9793988&dopt=Abstract
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Fetal cervico-mediastinal cystic hygroma associated with maternal serum screening positive for Down syndrome. Author(s): Chen CP, Sheu JC, Wang W, Lin SP, Chang TY, Tzen CY. Source: Prenatal Diagnosis. 2002 February; 22(2): 166. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11857633&dopt=Abstract
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Fetal Down syndrome screening: a cost effectiveness analysis of alternative screening programs. Author(s): Cusick W, Vintzileos AM. Source: The Journal of Maternal-Fetal Medicine. 1999 November-December; 8(6): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10582856&dopt=Abstract
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Fetal heart rate and nuchal translucency in detecting chromosomal abnormalities other than Down syndrome. Author(s): Martinez JM, Echevarria M, Borrell A, Puerto B, Ojuel J, Fortuny A. Source: Obstetrics and Gynecology. 1998 July; 92(1): 68-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9649096&dopt=Abstract
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Fetal life in Down syndrome starts with normal neuronal density but impaired dendritic spines and synaptosomal structure. Author(s): Weitzdoerfer R, Dierssen M, Fountoulakis M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 59-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771761&dopt=Abstract
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Fetal loss in Down syndrome pregnancies. Author(s): Snijders R. Source: Prenatal Diagnosis. 1999 December; 19(12): 1180. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10590443&dopt=Abstract
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Fetal loss in Down syndrome pregnancies. Author(s): Morris JK, Wald NJ, Watt HC. Source: Prenatal Diagnosis. 1999 February; 19(2): 142-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215072&dopt=Abstract
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Fetal nose bone length: a marker for Down syndrome in the second trimester. Author(s): Bromley B, Lieberman E, Shipp TD, Benacerraf BR. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2002 December; 21(12): 1387-94. Erratum In: J Ultrasound Med. 2003 February; 22(2): 162. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494981&dopt=Abstract
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Fetal nucleated red blood cell counts in peripheral blood of mothers bearing Down syndrome fetus. Author(s): Parano E, Falcidia E, Grillo A, Takabayashi H, Trifiletti RR, Pavone P. Source: Neuropediatrics. 2001 June; 32(3): 147-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11521211&dopt=Abstract
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Fetal transcerebellar diameter in Down syndrome. Author(s): Rotmensch S, Goldstein I, Liberati M, Shalev J, Ben-Rafael Z, Copel JA. Source: Obstetrics and Gynecology. 1997 April; 89(4): 534-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9083308&dopt=Abstract
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FGFR3 gene mutation (Gly380Arg) with achondroplasia and i(21q) Down syndrome: phenotype-genotype correlation. Author(s): Chen H, Mu X, Sonoda T, Kim KC, Dailey K, Martinez J, Tuck-Muller C, Wertelecki W. Source: Southern Medical Journal. 2000 June; 93(6): 622-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881785&dopt=Abstract
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Finger coordination in persons with Down syndrome: atypical patterns of coordination and the effects of practice. Author(s): Latash ML, Kang N, Patterson D. Source: Experimental Brain Research. Experimentelle Hirnforschung. Experimentation Cerebrale. 2002 October; 146(3): 345-55. Epub 2002 August 17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12232691&dopt=Abstract
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First information and support provided to parents of children with Down syndrome in Sweden: clinical goals and parental experiences. Author(s): Hedov G, Wikblad K, Anneren G. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(12): 1344-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578293&dopt=Abstract
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First trimester biochemical screening for Down syndrome: free beta hCG versus intact hCG. Author(s): Hallahan T, Krantz D, Orlandi F, Rossi C, Curcio P, Macri S, Larsen J, Buchanan P, Macri J. Source: Prenatal Diagnosis. 2000 October; 20(10): 785-9; Discussion 790-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11038453&dopt=Abstract
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First trimester Down Syndrome screening by nuchal translucency in a Thai population. Author(s): Panburana P, Ajjimakorn S, Tungkajiwangoon P. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2001 December; 75(3): 311-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11728495&dopt=Abstract
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First trimester Down syndrome screening markers in triploidy: a case report. Author(s): Campbell J, Cuckle H, Sehmi I, Jones R. Source: Prenatal Diagnosis. 1999 November; 19(11): 1086-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589071&dopt=Abstract
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First trimester screening for Down syndrome and assisted reproduction: no basis for concern. Author(s): Wojdemann KR, Larsen SO, Shalmi A, Sundberg K, Christiansen M, Tabor A. Source: Prenatal Diagnosis. 2001 July; 21(7): 563-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494292&dopt=Abstract
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First trimester spontaneous resolution of megacystis in a Down syndrome fetus. Author(s): Maymon R, Schneider D, Reish O, Herman A. Source: Prenatal Diagnosis. 2001 September; 21(9): 790-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559917&dopt=Abstract
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First trimester ultrasound with nuchal translucency measurement for Down syndrome risk estimation using software developed by the Fetal Medicine Foundation, United Kingdom--the first 2000 examinations in Newcastle, New South Wales, Australia. Author(s): O'Callaghan SP, Giles WB, Raymond SP, McDougall V, Morris K, Boyd J. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2000 August; 40(3): 292-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11065036&dopt=Abstract
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First-trimester biochemical markers for Down syndrome. Author(s): Casals E, Aibar C, Martinez JM, Borrell A, Soler A, Ojuel J, Ballesta AM, Fortuny A. Source: Prenatal Diagnosis. 1999 January; 19(1): 8-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10073898&dopt=Abstract
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First-trimester biochemical screening for Down syndrome with the use of PAPP-A, AFP, and beta-hCG. Author(s): Casals E, Fortuny A, Grudzinskas JG, Suzuki Y, Teisner B, Comas C, Sanllehy C, Ojuel J, Borrell A, Soler A, Ballesta AM. Source: Prenatal Diagnosis. 1996 May; 16(5): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8843997&dopt=Abstract
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First-trimester biochemical screening for Down syndrome. Author(s): Yaron Y, Mashiach R. Source: Clin Perinatol. 2001 June; 28(2): 321-31, Viii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499055&dopt=Abstract
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First-trimester Down syndrome screening using dried blood biochemistry and nuchal translucency. Author(s): Krantz DA, Hallahan TW, Orlandi F, Buchanan P, Larsen JW Jr, Macri JN. Source: Obstetrics and Gynecology. 2000 August; 96(2): 207-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10908764&dopt=Abstract
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First-trimester Down syndrome screening. Author(s): Macri JN, Orlandi F. Source: American Journal of Obstetrics and Gynecology. 2000 December; 183(6): 1591-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11120540&dopt=Abstract
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First-trimester Down syndrome screening: free beta-human chorionic gonadotropin and pregnancy-associated plasma protein A. Author(s): Krantz DA, Larsen JW, Buchanan PD, Macri JN. Source: American Journal of Obstetrics and Gynecology. 1996 February; 174(2): 612-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8623793&dopt=Abstract
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First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies. Author(s): Weinans MJ, Pratt JJ, de Wolf BT, Mantingh A. Source: Prenatal Diagnosis. 2001 September; 21(9): 723-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559906&dopt=Abstract
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First-trimester screening for Down syndrome using nuchal translucency measurement with free beta-hCG and PAPP-A between 10 and 13 weeks of pregnancy--the combined test. Author(s): De Biasio P, Siccardi M, Volpe G, Famularo L, Santi F, Canini S. Source: Prenatal Diagnosis. 1999 April; 19(4): 360-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327142&dopt=Abstract
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Fluorescence in situ hybridization of chorionic interphase cells for prenatal screening of Down syndrome. Author(s): Toth A, Tardy EP, Hajdu K, Batorfi J, Doszpod J, Egyed J, Gati I. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 2001 January; 94(1): 46-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11134825&dopt=Abstract
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Folate and homocysteine metabolism and gene polymorphisms in the etiology of Down syndrome. Author(s): Rosenblatt DS. Source: The American Journal of Clinical Nutrition. 1999 October; 70(4): 429-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500007&dopt=Abstract
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Free beta-hCG subunit versus intact hCG in Down syndrome screening. Author(s): Wenstrom KD, Owen J, Chu DC, Boots L. Source: Obstetrics and Gynecology. 1997 September; 90(3): 370-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9277646&dopt=Abstract
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Frequency of cardiovascular and gastrointestinal malformations, leukemia and hypothyroidism in children with Down syndrome in Trabzon, Turkey. Author(s): Aynaci FM, Orhan F, Celep F, Karaguzel A. Source: Turk J Pediatr. 1998 January-March; 40(1): 103-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9673536&dopt=Abstract
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Frequency of celiac disease in individuals with Down syndrome in the United States. Author(s): Mackey J, Treem WR, Worley G, Boney A, Hart P, Kishnani PS. Source: Clinical Pediatrics. 2001 May; 40(5): 249-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11388673&dopt=Abstract
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Functional genomics of Down syndrome: a multidisciplinary approach. Author(s): Dierssen M, Marti E, Pucharcos C, Fotaki V, Altafaj X, Casas K, Solans A, Arbones ML, Fillat C, Estivill X. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 131-48. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771739&dopt=Abstract
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Functional genomics of the Down syndrome. Author(s): Nizetic D. Source: Croatian Medical Journal. 2001 August; 42(4): 421-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11471193&dopt=Abstract
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Functional screening of 2 Mb of human chromosome 21q22.2 in transgenic mice implicates minibrain in learning defects associated with Down syndrome. Author(s): Smith DJ, Stevens ME, Sudanagunta SP, Bronson RT, Makhinson M, Watabe AM, O'Dell TJ, Fung J, Weier HU, Cheng JF, Rubin EM. Source: Nature Genetics. 1997 May; 16(1): 28-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9140392&dopt=Abstract
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Functional status of school-aged children with Down syndrome. Author(s): Leonard S, Msall M, Bower C, Tremont M, Leonard H. Source: Journal of Paediatrics and Child Health. 2002 April; 38(2): 160-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030998&dopt=Abstract
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GATA1 mutations in transient leukemia and acute megakaryoblastic leukemia of Down syndrome. Author(s): Hitzler JK, Cheung J, Li Y, Scherer SW, Zipursky A. Source: Blood. 2003 June 1; 101(11): 4301-4. Epub 2003 February 13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12586620&dopt=Abstract
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Gender differences in coping strategies of parents of children with Down syndrome. Author(s): Sullivan A. Source: Downs Syndr Res Pract. 2002 September; 8(2): 67-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407971&dopt=Abstract
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Gender impact on first trimester markers in Down syndrome screening. Author(s): Larsen SO, Wojdemann KR, Shalmi AC, Sundberg K, Christiansen M, Tabor A. Source: Prenatal Diagnosis. 2002 December; 22(13): 1207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478634&dopt=Abstract
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Gene expression in fetal Down syndrome brain as revealed by subtractive hybridization. Author(s): Labudova O, Kitzmueller E, Rink H, Cairns N, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 125-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666672&dopt=Abstract
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Gene expression relevant to Down syndrome: problems and approaches. Author(s): Tassone F, Lucas R, Slavov D, Kavsan V, Crnic L, Gardiner K. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 179-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666675&dopt=Abstract
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Gene identification in 1.6-Mb region of the Down syndrome region on chromosome 21. Author(s): Ohira M, Seki N, Nagase T, Suzuki E, Nomura N, Ohara O, Hattori M, Sakaki Y, Eki T, Murakami Y, Saito T, Ichikawa H, Ohki M. Source: Genome Research. 1997 January; 7(1): 47-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9037601&dopt=Abstract
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Gene polymorphism and folate metabolism: a maternal risk factor for Down syndrome. Author(s): Sheth JJ, Sheth FJ. Source: Indian Pediatrics. 2003 February; 40(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12626825&dopt=Abstract
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Genetic dissection of region associated with behavioral abnormalities in mouse models for Down syndrome. Author(s): Sago H, Carlson EJ, Smith DJ, Rubin EM, Crnic LS, Huang TT, Epstein CJ. Source: Pediatric Research. 2000 November; 48(5): 606-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11044479&dopt=Abstract
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Genetic predisposition to ventricular septal defect in Down syndrome. Author(s): Digilio MC, Marino B. Source: Human Genetics. 2001 October; 109(4): 463. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11702228&dopt=Abstract
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Genomic instability in Down syndrome and Fanconi anemia assessed by micronucleus analysis and single-cell gel electrophoresis. Author(s): Maluf SW, Erdtmann B. Source: Cancer Genetics and Cytogenetics. 2001 January 1; 124(1): 71-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165325&dopt=Abstract
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Genomic organization, alternative splicing, and expression patterns of the DSCR1 (Down syndrome candidate region 1) gene. Author(s): Fuentes JJ, Pritchard MA, Estivill X. Source: Genomics. 1997 September 15; 44(3): 358-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9325060&dopt=Abstract
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Germinoma in cerebral hemisphere associated with Down syndrome. Author(s): Nakashima T, Nishimura Y, Sakai N, Yamada H, Hara A. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1997 October; 13(10): 563-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9403208&dopt=Abstract
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Gestures and words in early development of children with Down syndrome. Author(s): Caselli MC, Vicari S, Longobardi E, Lami L, Pizzoli C, Stella G. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 1998 October; 41(5): 1125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9771634&dopt=Abstract
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Getting in and staying there: children with Down syndrome in mainstream schools. Author(s): Cuckle P. Source: Downs Syndr Res Pract. 1999 September; 6(2): 95-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11276984&dopt=Abstract
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Glial-neurotrophic mechanisms in Down syndrome. Author(s): Nelson PG, McCune SK, Ades AM, Nelson KB. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 85-94. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771763&dopt=Abstract
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Glomerulonephritis in children with Down syndrome. Author(s): Birk PE, Burke BA, Vernier RL. Source: Pediatric Nephrology (Berlin, Germany). 1996 August; 10(4): 549. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8865268&dopt=Abstract
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Glutathione metabolism and antioxidant enzymes in children with Down syndrome. Author(s): Pastore A, Tozzi G, Gaeta LM, Giannotti A, Bertini E, Federici G, Digilio MC, Piemonte F. Source: The Journal of Pediatrics. 2003 May; 142(5): 583-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12756395&dopt=Abstract
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Gonadal function in young women with Down syndrome. Author(s): Angelopoulou N, Souftas V, Sakadamis A, Matziari C, Papameletiou V, Mandroukas K. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 1999 October; 67(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10576235&dopt=Abstract
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Gross motor function of children with down syndrome: creation of motor growth curves. Author(s): Palisano RJ, Walter SD, Russell DJ, Rosenbaum PL, Gemus M, Galuppi BE, Cunningham L. Source: Archives of Physical Medicine and Rehabilitation. 2001 April; 82(4): 494-500. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11295010&dopt=Abstract
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Growth and pubertal development in Down syndrome. Author(s): Arnell H, Gustafsson J, Ivarsson SA, Anneren G. Source: Acta Paediatrica (Oslo, Norway : 1992). 1996 September; 85(9): 1102-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8888926&dopt=Abstract
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Growth curves of children with Down syndrome. Author(s): Toledo C, Alembik Y, Aguirre Jaime A, Stoll C. Source: Annales De Genetique. 1999; 42(2): 81-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10434121&dopt=Abstract
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Growth hormone administration normalizes the ovarian responsiveness to folliclestimulating-hormone in the early stages of the follicular maturation in women with Down syndrome. Author(s): Cento RM, Ragusa L, Proto C, Alberti A, Fiore G, Soranna L, Colabucci F, Lanzone A. Source: J Endocrinol Invest. 1998 June; 21(6): 342-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9699124&dopt=Abstract
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Growth hormone therapy in young children with Down syndrome and a clinical comparison of Down and Prader-Willi syndromes. Author(s): Anneren G, Tuvemo T, Gustafsson J. Source: Growth Hormone & Igf Research : Official Journal of the Growth Hormone Research Society and the International Igf Research Society. 2000 April; 10 Suppl B: S8791. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10984260&dopt=Abstract
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Guidelines for optimal medical care of persons with Down syndrome. International League of Societies for Persons with Mental Handicap (ILSMH). Author(s): Pueschel SM, Anneren G, Durlach R, Flores J, Sustrova M, Verma IC. Source: Acta Paediatrica (Oslo, Norway : 1992). 1995 July; 84(7): 823-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7549308&dopt=Abstract
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hCG and the free beta-subunit as screening tests for Down syndrome. Author(s): Knight GJ, Palomaki GE, Neveux LM, Fodor KK, Haddow JE. Source: Prenatal Diagnosis. 1998 March; 18(3): 235-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556040&dopt=Abstract
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Health care concerns and guidelines for adults with Down syndrome. Author(s): van Allen MI, Fung J, Jurenka SB. Source: American Journal of Medical Genetics. 1999 June 25; 89(2): 100-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10559765&dopt=Abstract
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Health maintenance throughout the life span for individuals with Down syndrome. Author(s): Bosch JJ. Source: Journal of the American Academy of Nurse Practitioners. 2003 January; 15(1): 517. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12613408&dopt=Abstract
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Health supervision for children with Down syndrome. Author(s): Marino B, Digilio MC, Di Donato R. Source: Pediatrics. 2001 December; 108(6): 1384; Author Reply 1385. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757553&dopt=Abstract
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Health supervision for children with Down syndrome. Author(s): Feingold M, Geggel RL. Source: Pediatrics. 2001 December; 108(6): 1384; Author Reply 1385. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731668&dopt=Abstract
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Hearing loss in children with Down syndrome. Author(s): Shott SR, Joseph A, Heithaus D. Source: International Journal of Pediatric Otorhinolaryngology. 2001 December 1; 61(3): 199-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11700189&dopt=Abstract
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Heat stable and urea resistant alkaline phosphatase in maternal neutrophils from normal and Down syndrome pregnancies. Author(s): Peleg L, Ries L, Getslev V, Lusky A, Chaki R, Lipitz S, Barkai G. Source: Prenatal Diagnosis. 1999 March; 19(3): 224-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210120&dopt=Abstract
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Heat-shock protein 70 levels in brain of patients with Down syndrome and Alzheimer's disease. Author(s): Yoo BC, Seidl R, Cairns N, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 315-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666686&dopt=Abstract
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Hematological studies in children with Down syndrome. Author(s): David O, Fiorucci GC, Tosi MT, Altare F, Valori A, Saracco P, Asinardi P, Ramenghi U, Gabutti V. Source: Pediatric Hematology and Oncology. 1996 May-June; 13(3): 271-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8735344&dopt=Abstract
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Hematopoietic deficiencies and core binding factor expression in murine Ts16, an animal model for Down syndrome. Author(s): Gjertson C, Sturm KS, Berger CN. Source: Clinical Immunology (Orlando, Fla.). 1999 April; 91(1): 50-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10219254&dopt=Abstract
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Hemophagocytosis and granulomas in the bone marrow of a child with Down syndrome. Author(s): Sakhalkar VS, Rao SP, Gottessman SR, Miller ST. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 December; 23(9): 623-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11902310&dopt=Abstract
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Hepatitis B and C infection in children with Down syndrome. Author(s): Piccione M, De Curtis M, La Vecchia ML, Novissimo A, Vajro P. Source: European Journal of Pediatrics. 1997 May; 156(5): 420-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9177993&dopt=Abstract
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Heterotrisomy, a significant contributing factor to ventricular septal defect associated with Down syndrome? Author(s): Baptista MJ, Fairbrother UL, Howard CM, Farrer MJ, Davies GE, Trikka D, Maratou K, Redington A, Greve G, Njolstad PR, Kessling AM. Source: Human Genetics. 2000 November; 107(5): 476-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11140945&dopt=Abstract
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High expression of platelet-derived growth factor and transforming growth factorbeta 1 in blast cells from patients with Down Syndrome suffering from transient myeloproliferative disorder and organ fibrosis. Author(s): Hattori H, Matsuzaki A, Suminoe A, Ihara K, Nakayama H, Hara T. Source: British Journal of Haematology. 2001 November; 115(2): 472-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11703351&dopt=Abstract
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High frequency of celiac disease in Down syndrome. Author(s): George EK, Mearin ML, Bouquet J, von Blomberg BM, Stapel SO, van Elburg RM, de Graaf EA. Source: The Journal of Pediatrics. 1996 April; 128(4): 555-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8618192&dopt=Abstract
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High frequency of the 844ins68 cystathionine-beta-synthase gene variant in Down syndrome children with acute myeloid leukemia. Author(s): Ge Y, Jensen T, James SJ, Becton DL, Massey GV, Weinstein HJ, Ravindranath Y, Matherly LH, Taub JW. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 November; 16(11): 2339-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399985&dopt=Abstract
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High immunocontent of S100 beta protein in amniotic fluid of pregnancies with Down syndrome. Author(s): Portela LC, Tort AB, Neto EC, Kessler RG, Penchaszadeh V, Souza DO, Goncalves CA, Giugliani R. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2000 November; 16(6): 590-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11220205&dopt=Abstract
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High levels of maternal serum human chorionic gonadotropin in Down syndrome pregnancies: the possible role of a transcription factor on chromosome 21. Author(s): Goshen R, Gonik B, Ariel I, Weiss Y, de-Groot N, Hochberg A. Source: Fetal Diagnosis and Therapy. 1999 March-April; 14(2): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10085509&dopt=Abstract
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High maternal serum free beta-hCG levels in Down syndrome pregnancies: a preliminary report. Author(s): Hsu JJ, Ou YC, Chen KC, Hsieh TT, Soong YK. Source: Changgeng Yi Xue Za Zhi. 1996 March; 19(1): 36-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8935373&dopt=Abstract
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High resolution physical mapping and identification of transcribed sequences in the Down syndrome region-2. Author(s): Vidal-Taboada JM, Bergonon S, Sanchez M, Lopez-Acedo C, Groet J, Nizetic D, Egeo A, Scartezzini P, Katsanis N, Fisher EM, Delabar JM, Oliva R. Source: Biochemical and Biophysical Research Communications. 1998 February 13; 243(2): 572-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9480850&dopt=Abstract
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High serum endostatin levels in Down syndrome: implications for improved treatment and prevention of solid tumours. Author(s): Zorick TS, Mustacchi Z, Bando SY, Zatz M, Moreira-Filho CA, Olsen B, Passos-Bueno MR. Source: European Journal of Human Genetics : Ejhg. 2001 November; 9(11): 811-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11781696&dopt=Abstract
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Highly polymorphic sequence at D21S1448 mapping close to D21S55, within the Down syndrome critical region. Author(s): Hernandez D, Pannett AA, Tybulewicz V, Fisher EM. Source: Human Genetics. 1995 June; 95(6): 721-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7789964&dopt=Abstract
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High-resolution physical map and identification of potentially regulatory sequences of the human SH3BGR located in the Down syndrome chromosomal region. Author(s): Vidal-Taboada JM, Bergonon S, Scartezzini P, Egeo A, Nizetic D, Oliva R. Source: Biochemical and Biophysical Research Communications. 1997 December 18; 241(2): 321-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9425270&dopt=Abstract
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Hodgkin's disease in association with Down syndrome: a case report. Author(s): Kusumakumary P, Jyothirmayi R, Chellam VG, Krishnan NM. Source: Pediatric Hematology and Oncology. 1996 September-October; 13(5): 469-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10897820&dopt=Abstract
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Homocysteine metabolism in children with Down syndrome: in vitro modulation. Author(s): Pogribna M, Melnyk S, Pogribny I, Chango A, Yi P, James SJ. Source: American Journal of Human Genetics. 2001 July; 69(1): 88-95. Epub 2001 June 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11391481&dopt=Abstract
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Horizontal-plane arm movements with direction reversals performed by normal individuals and individuals with down syndrome. Author(s): Almeida GL, Corcos DM, Hasan Z. Source: Journal of Neurophysiology. 2000 October; 84(4): 1949-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11024088&dopt=Abstract
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How accurate is a second-trimester prenatal ultrasound in the diagnosis of Down syndrome? Author(s): Smalley C. Source: The Journal of Family Practice. 2001 June; 50(6): 490. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401731&dopt=Abstract
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How frequent is coeliac disease in Down syndrome? Author(s): Sanchez-Albisua I, Storm W, Wascher I, Stern M. Source: European Journal of Pediatrics. 2002 December; 161(12): 683-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12536992&dopt=Abstract
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How women deal with the results of serum screening for Down syndrome in the second trimester of pregnancy. Author(s): Weinans MJ, Huijssoon AM, Tymstra T, Gerrits MC, Beekhuis JR, Mantingh A. Source: Prenatal Diagnosis. 2000 September; 20(9): 705-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11015697&dopt=Abstract
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Human brain cytosolic histamine-N-methyltransferase is decreased in Down syndrome and increased in Pick's disease. Author(s): Kim SH, Krapfenbauer K, Cheon MS, Fountoulakis M, Cairns NJ, Lubec G. Source: Neuroscience Letters. 2002 March 22; 321(3): 169-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11880199&dopt=Abstract
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Human brain nascent polypeptide-associated complex alpha subunit is decreased in patients with Alzheimer' s disease and Down syndrome. Author(s): Kim SH, Shim KS, Lubec G. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2002 July; 50(4): 293-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109594&dopt=Abstract
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Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer's disease and Down syndrome. Author(s): Kim SH, Fountoulakis M, Cairns NJ, Lubec G. Source: Biochemical and Biophysical Research Communications. 2002 August 30; 296(4): 970-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200143&dopt=Abstract
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Human minibrain homologue (MNBH/DYRK1): characterization, alternative splicing, differential tissue expression, and overexpression in Down syndrome. Author(s): Guimera J, Casas C, Estivill X, Pritchard M. Source: Genomics. 1999 May 1; 57(3): 407-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10329007&dopt=Abstract
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Hydrops fetalis and neonatal leukemia in Down syndrome. Author(s): Zipursky A, Rose T, Skidmore M, Thorner P, Doyle J. Source: Pediatric Hematology and Oncology. 1996 January-February; 13(1): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8718505&dopt=Abstract
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Hypercalcaemia, hypercalciuria and nephrocalcinosis in Down syndrome. Author(s): Proesmans W. Source: Pediatric Nephrology (Berlin, Germany). 1996 August; 10(4): 543-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8865263&dopt=Abstract
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Hypercalcemia, hypercalciuria, medullar nephrocalcinosis, and renal insufficiency in a toddler with Down syndrome. Author(s): Andreoli SP, Revkees S, Bull M. Source: Pediatric Nephrology (Berlin, Germany). 1995 October; 9(5): 673. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8580039&dopt=Abstract
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Hyperechogenic fetal bowel and Down syndrome. Results of a French collaborative study based on 680 prospective cases. Author(s): Simon-Bouy B, Muller F; French Collaborative Group. Source: Prenatal Diagnosis. 2002 March; 22(3): 189-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920891&dopt=Abstract
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Hyperglycosylated hCG, a potential alternative to hCG in Down syndrome screening. Author(s): Cole LA, Omrani A, Cermik D, Singh RO, Mahoney MJ. Source: Prenatal Diagnosis. 1998 September; 18(9): 926-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9793975&dopt=Abstract
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Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: A new basis for gestational Down syndrome screening. Author(s): Cole LA, Shahabi S, Oz UA, Bahado-Singh RO, Mahoney MJ. Source: Clinical Chemistry. 1999 December; 45(12): 2109-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10585342&dopt=Abstract
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Identification and cloning of a novel cDNA belonging to tetratricopeptide repeat gene family from Down syndrome-critical region 21q22.2. Author(s): Tsukahara F, Hattori M, Muraki T, Sakaki Y. Source: Journal of Biochemistry. 1996 October; 120(4): 820-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8947847&dopt=Abstract
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Identification of a novel human gene containing the tetratricopeptide repeat domain from the Down syndrome region of chromosome 21. Author(s): Ohira M, Ootsuyama A, Suzuki E, Ichikawa H, Seki N, Nagase T, Nomura N, Ohki M. Source: Dna Res. 1996 February 29; 3(1): 9-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8724848&dopt=Abstract
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IGF-I levels in prepubertal and pubertal children with Down syndrome. Author(s): Ragusa L, Valetto MR, Proto C, Alberti A, Romano C, Rossodivita A, Corneli G, Baffoni C, Lanfranco F, Aimaretti G, Colabucci F, Ghigo E. Source: Minerva Endocrinol. 1998 June; 23(2): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9844353&dopt=Abstract
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Iliac angle as a marker for Down syndrome in second-trimester fetuses: CT measurement. Author(s): Zook PD, Winter TC 3rd, Nyberg DA. Source: Radiology. 1999 May; 211(2): 447-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10228527&dopt=Abstract
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Imitation of pretend play acts by children with autism and Down syndrome. Author(s): Libby S, Powell S, Messer D, Jordan R. Source: Journal of Autism and Developmental Disorders. 1997 August; 27(4): 365-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9261664&dopt=Abstract
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Impact of prenatal diagnosis on revised livebirth prevalence estimates of Down syndrome in the Lothian region of Scotland, 1978-1992. Author(s): Huether CA, Haroldson K, Ellis PM, Ramsay CN. Source: Genetic Epidemiology. 1996; 13(4): 367-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8894639&dopt=Abstract
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Impact of prenatal diagnosis on the prevalence of live births with Down syndrome in the eastern half of Switzerland 1980-1996. Author(s): Binkert F, Mutter M, Schinzel A. Source: Swiss Medical Weekly : Official Journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology. 2002 August 24; 132(33-34): 478-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12458448&dopt=Abstract
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Impact of prenatal screening on the birth status of fetuses with Down syndrome at an urban hospital, 1972-1994. Author(s): Caruso TM, Westgate MN, Holmes LB. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 1998 November-December; 1(1): 22-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261425&dopt=Abstract
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Impact of routine fetal ultrasonographic screening on the prevalence of Down syndrome in non aged mothers. Author(s): Stoll C, Alembik Y, Dott B. Source: Annales De Genetique. 1998; 41(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9599648&dopt=Abstract
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Impaired brain glucose metabolism in patients with Down syndrome. Author(s): Labudova O, Cairns N, Kitzmuller E, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 247-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666680&dopt=Abstract
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Impaired Ca-signaling in astrocytes from the Ts16 mouse model of Down syndrome. Author(s): Muller W, Heinemann U, Schuchmann S. Source: Neuroscience Letters. 1997 February 21; 223(2): 81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9089678&dopt=Abstract
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Impaired short- and long-term memory in Ts65Dn mice, a model for Down syndrome. Author(s): Escorihuela RM, Vallina IF, Martinez-Cue C, Baamonde C, Dierssen M, Tobena A, Florez J, Fernandez-Teruel A. Source: Neuroscience Letters. 1998 May 15; 247(2-3): 171-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9655620&dopt=Abstract
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Implicit and explicit memory: a functional dissociation in persons with Down syndrome. Author(s): Vicari S, Bellucci S, Carlesimo GA. Source: Neuropsychologia. 2000; 38(3): 240-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10678691&dopt=Abstract
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In vivo brain myo-inositol levels in children with Down syndrome. Author(s): Berry GT, Wang ZJ, Dreha SF, Finucane BM, Zimmerman RA. Source: The Journal of Pediatrics. 1999 July; 135(1): 94-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10393611&dopt=Abstract
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Inaccurate estimation of risk in second trimester serum screening for Down syndrome among women who have already had first trimester screening. Author(s): Hackshaw AK, Wald NJ. Source: Prenatal Diagnosis. 2001 September; 21(9): 741-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11559910&dopt=Abstract
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Incidence and mortality of Down syndrome. Author(s): Merrick J. Source: Isr Med Assoc J. 2000 January; 2(1): 25-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10892367&dopt=Abstract
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Incidence of leukemia and other cancers in Down syndrome subjects in Israel. Author(s): Boker LK, Blumstein T, Sadetzki S, Luxenburg O, Litvak I, Akstein E, Modan B. Source: International Journal of Cancer. Journal International Du Cancer. 2001 September 1; 93(5): 741-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11477589&dopt=Abstract
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Inclusion of serum marker measurements from a previous pregnancy improves Down syndrome screening performance. Author(s): Larsen SO, Christiansen M, Norgaard-Pedersen B. Source: Prenatal Diagnosis. 1998 July; 18(7): 706-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706652&dopt=Abstract
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Incorporation of inhibin-A in second-trimester screening for Down syndrome. Author(s): Hallahan TW, Krantz DA, Macri JN. Source: Obstetrics and Gynecology. 2003 August; 102(2): 413; Author Reply 413-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12907120&dopt=Abstract
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Incorporation of inhibin-A in second-trimester screening for Down syndrome. Author(s): Benn PA, Fang M, Egan JF, Horne D, Collins R. Source: Obstetrics and Gynecology. 2003 March; 101(3): 451-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12636947&dopt=Abstract
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Increased concentrations of prostate-specific antigen in maternal serum from pregnancies affected by fetal Down syndrome. Author(s): Lambert-Messerlian GM, Canick JA, Melegos DN, Diamandis EP. Source: Clinical Chemistry. 1998 February; 44(2): 205-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9474012&dopt=Abstract
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Increased kynurenic acid levels and decreased brain kynurenine aminotransferase I in patients with Down syndrome. Author(s): Baran H, Cairns N, Lubec B, Lubec G. Source: Life Sciences. 1996; 58(21): 1891-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8637415&dopt=Abstract
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Increased levels of 14-3-3 gamma and epsilon proteins in brain of patients with Alzheimer's disease and Down syndrome. Author(s): Fountoulakis M, Cairns N, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 323-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666687&dopt=Abstract
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Increased levels of a chromosome 21-encoded tumour invasion and metastasis factor (TIAM1) mRNA in bone marrow of Down syndrome children during the acute phase of AML(M7). Author(s): Ives JH, Dagna-Bricarelli F, Basso G, Antonarakis SE, Jee R, Cotter F, Nizetic D. Source: Genes, Chromosomes & Cancer. 1998 September; 23(1): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9713998&dopt=Abstract
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Increased levels of mutagen-induced chromosome breakage in Down syndrome children with malignancy. Author(s): Ankathil R, Kusumakumary P, Nair MK. Source: Cancer Genetics and Cytogenetics. 1997 December; 99(2): 126-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9398867&dopt=Abstract
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Increased levels of tau-like protein in patients with Down syndrome. Author(s): Mehta PD, Patrick BA, Dalton AJ, Aisen PS, Emmerling ME, Sersen EA, Wisniewski HM. Source: Neuroscience Letters. 1999 November 19; 275(3): 159-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10580699&dopt=Abstract
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Increased low-level chromosome 21 mosaicism in older individuals with Down syndrome. Author(s): Jenkins EC, Schupf N, Genovese M, Ye LL, Kapell D, Canto B, Harris M, Devenny D, Lee JH, Brown WT. Source: American Journal of Medical Genetics. 1997 January 20; 68(2): 147-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9028448&dopt=Abstract
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Increased plasma amyloid beta protein 1-42 levels in Down syndrome. Author(s): Mehta PD, Dalton AJ, Mehta SP, Kim KS, Sersen EA, Wisniewski HM. Source: Neuroscience Letters. 1998 January 23; 241(1): 13-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9502204&dopt=Abstract
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Increased protein levels of serotonin transporter in frontal cortex of patients with Down syndrome. Author(s): Gulesserian T, Engidawork E, Cairns N, Lubec G. Source: Neuroscience Letters. 2000 December 15; 296(1): 53-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11099832&dopt=Abstract
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Increased RNA levels of the 25 kDa synaptosomal associated protein in brain samples of adult patients with Down Syndrome. Author(s): Greber-Platzer S, Fleischmann C, Nussbaumer C, Cairns N, Lubec G. Source: Neuroscience Letters. 2003 January 16; 336(2): 77-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12499044&dopt=Abstract
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Increased steady state mRNA levels of DNA-repair genes XRCC1, ERCC2 and ERCC3 in brain of patients with Down syndrome. Author(s): Fang-Kircher SG, Labudova O, Kitzmueller E, Rink H, Cairns N, Lubec G. Source: Life Sciences. 1999; 64(18): 1689-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10328528&dopt=Abstract
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Index of suspicion. Case 2. Diagnosis: mosaic Down syndrome. Author(s): Barron SA, Malinich T. Source: Pediatrics in Review / American Academy of Pediatrics. 2001 March; 22(3): 95103. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11419387&dopt=Abstract
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Infantile spasms in Down syndrome: good response to a short course of vigabatrin. Author(s): Nabbout R, Melki I, Gerbaka B, Dulac O, Akatcherian C. Source: Epilepsia. 2001 December; 42(12): 1580-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11879370&dopt=Abstract
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Infants with Down syndrome: a look at temperament. Author(s): Zickler CF, Morrow JD, Bull MJ. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 1998 May-June; 12(3): 111-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9652278&dopt=Abstract
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Influence of age on activities of antioxidant enzymes and lipid peroxidation products in erythrocytes and neutrophils of Down syndrome patients. Author(s): Muchova J, Sustrova M, Garaiova I, Liptakova A, Blazicek P, Kvasnicka P, Pueschel S, Durackova Z. Source: Free Radical Biology & Medicine. 2001 August 15; 31(4): 499-508. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11498283&dopt=Abstract
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Influence of child diagnosis on family and parental functioning: Down syndrome versus other disabilities. Author(s): Cahill BM, Glidden LM. Source: Am J Ment Retard. 1996 September; 101(2): 149-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8883669&dopt=Abstract
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Informed consent to serum screening for Down syndrome: are women given adequate information? Author(s): Gekas J, Gondry J, Mazur S, Cesbron P, Thepot F. Source: Prenatal Diagnosis. 1999 January; 19(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10073897&dopt=Abstract
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Inhibin-B and pro-alphaC-containing inhibins in amniotic fluid from chromosomally normal and Down syndrome pregnancies. Author(s): Wallace EM, Crossley JA, Riley SC, Balfour C, Groome NP, Aitken DA. Source: Prenatal Diagnosis. 1998 March; 18(3): 213-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556037&dopt=Abstract
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Inositol monophosphatase activity in normal, Down syndrome and dementia of the Alzheimer type CSF. Author(s): Atack JR, Schapiro MB. Source: Neurobiology of Aging. 2002 May-June; 23(3): 389-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11959401&dopt=Abstract
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Insulin-like growth factor binding protein-3 in the detection of fetal Down syndrome pregnancies. Author(s): Chu DC, Hsu C, Wenstrom KD, Boots LR. Source: Obstetrics and Gynecology. 1998 February; 91(2): 192-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9469274&dopt=Abstract
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Interferon action and chromosome 21 trisomy (Down syndrome): 15 years later. Author(s): Maroun LE. Source: Journal of Theoretical Biology. 1996 July 7; 181(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8796190&dopt=Abstract
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International variation in reported livebirth prevalence rates of Down syndrome, adjusted for maternal age. Author(s): Carothers AD, Hecht CA, Hook EB. Source: Journal of Medical Genetics. 1999 May; 36(5): 386-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10353785&dopt=Abstract
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Interphase FISH for rapid identification of a down syndrome animal model. Author(s): Strovel J, Stamberg J, Yarowsky PJ. Source: Cytogenetics and Cell Genetics. 1999; 86(3-4): 285-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10575227&dopt=Abstract
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Intestinal microvillous atrophy in a patient with Down syndrome and aganglionic megacolon. Author(s): Martinez MA, Egea AS, Lopez JM, Benitez EM. Source: Ultrastructural Pathology. 2002 January-February; 26(1): 41-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12028658&dopt=Abstract
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Intraneuronal Abeta42 accumulation in Down syndrome brain. Author(s): Mori C, Spooner ET, Wisniewsk KE, Wisniewski TM, Yamaguch H, Saido TC, Tolan DR, Selkoe DJ, Lemere CA. Source: Amyloid. 2002 June; 9(2): 88-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12440481&dopt=Abstract
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Intraneuronal abeta-amyloid precedes development of amyloid plaques in Down syndrome. Author(s): Gyure KA, Durham R, Stewart WF, Smialek JE, Troncoso JC. Source: Archives of Pathology & Laboratory Medicine. 2001 April; 125(4): 489-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260621&dopt=Abstract
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Is arthritis more common in children with Down syndrome? Author(s): Padmakumar B, Evans Jones LG, Sills JA. Source: Rheumatology (Oxford, England). 2002 October; 41(10): 1191-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12364643&dopt=Abstract
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Is Down syndrome a risk factor for poor outcome after repair of congenital heart defects? Author(s): Reller MD, Morris CD. Source: The Journal of Pediatrics. 1998 April; 132(4): 738-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9580782&dopt=Abstract
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Is maternal serum triple screening a better predictor of Down syndrome in female than in male fetuses? Author(s): Ghidini A, Spong CY, Grier RE, Walker CN, Pezzullo JC. Source: Prenatal Diagnosis. 1998 February; 18(2): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9516012&dopt=Abstract
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Is prostate-specific antigen a marker for pregnancies affected by Down syndrome? Author(s): Spencer K, Carpenter P. Source: Clinical Chemistry. 1998 November; 44(11): 2362-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9799767&dopt=Abstract
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Is there an association of Down Syndrome and omphalocele? Author(s): Mastroiacovo P, Robert E, Kallen B. Source: American Journal of Medical Genetics. 1999 February 19; 82(5): 443. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10069720&dopt=Abstract
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Is there an association of Down syndrome and omphalocele? Author(s): Torfs CP, Honore LH, Curry CJ. Source: American Journal of Medical Genetics. 1997 December 31; 73(4): 400-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9415464&dopt=Abstract
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Is there evidence of clustering in Down syndrome? Author(s): Morris JK, Alberman E, Mutton D. Source: International Journal of Epidemiology. 1998 June; 27(3): 495-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698142&dopt=Abstract
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Isoenzymes of maternal serum alkaline phosphatase in Down syndrome. Author(s): Cuckle HS, Miller D, Hossein Nia M, Gordon DJ, Holt DW. Source: Prenatal Diagnosis. 1998 April; 18(4): 409-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9602493&dopt=Abstract
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Isolated fetal pyelectasis: assessment of risk for postnatal uropathy and Down syndrome. Author(s): Wickstrom E, Maizels M, Sabbagha RE, Tamura RK, Cohen LC, Pergament E. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 1996 October; 8(4): 236-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916375&dopt=Abstract
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Isolation and analysis of chromosome 21 genes potentially involved in Down syndrome. Author(s): Gosset P, Ait-Ghezala G, Sinet PM, Creau N. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 197-209. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666676&dopt=Abstract
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Isolation of a novel human gene from the Down syndrome critical region of chromosome 21q22.2. Author(s): Nakamura A, Hattori M, Sakaki Y. Source: Journal of Biochemistry. 1997 October; 122(4): 872-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9399594&dopt=Abstract
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Isolation of human and murine homologues of the Drosophila minibrain gene: human homologue maps to 21q22.2 in the Down syndrome “critical region”. Author(s): Song WJ, Sternberg LR, Kasten-Sportes C, Keuren ML, Chung SH, Slack AC, Miller DE, Glover TW, Chiang PW, Lou L, Kurnit DM. Source: Genomics. 1996 December 15; 38(3): 331-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8975710&dopt=Abstract
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Isolation of two novel genes, DSCR5 and DSCR6, from Down syndrome critical region on human chromosome 21q22.2. Author(s): Shibuya K, Kudoh J, Minoshima S, Kawasaki K, Asakawa S, Shimizu N. Source: Biochemical and Biophysical Research Communications. 2000 May 19; 271(3): 693-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10814524&dopt=Abstract
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Jejunal angiomatoses causing small bowel obstruction in a patient with Down syndrome: a case report. Author(s): Patankar T, Prasad S, Joshi A, Deshmukh H. Source: Journal of Postgraduate Medicine. 1998 January-March; 44(1): 16-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10703561&dopt=Abstract
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Joint attention and language gains in children with Down syndrome. Author(s): Harris S, Kasari C, Sigman MD. Source: Am J Ment Retard. 1996 May; 100(6): 608-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8735574&dopt=Abstract
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Joint estimation of Down syndrome risk and ascertainment rates: a meta-analysis of nine published data sets. Author(s): Bray I, Wright DE, Davies C, Hook EB. Source: Prenatal Diagnosis. 1998 January; 18(1): 9-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9483635&dopt=Abstract
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Karyotypes found in the population declared at increased risk of Down syndrome following maternal serum screening. Author(s): Ryall RG, Callen D, Cocciolone R, Duvnjak A, Esca R, Frantzis N, Gjerde EM, Haan EA, Hocking T, Sutherland G, Thomas DW, Webb F. Source: Prenatal Diagnosis. 2001 July; 21(7): 553-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494290&dopt=Abstract
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Knowledge of Down syndrome in pregnant women from different ethnic groups. Author(s): Chilaka VN, Konje JC, Stewart CR, Narayan H, Taylor DJ. Source: Prenatal Diagnosis. 2001 March; 21(3): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260600&dopt=Abstract
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Lack of age-associated LFA-1 up-regulation and impaired ICAM-1 binding in lymphocytes from patients with Down syndrome. Author(s): Lin SJ, Wang JY, Klickstein LB, Chuang KP, Chen JY, Lee JF, Shieh CC. Source: Clinical and Experimental Immunology. 2001 October; 126(1): 54-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11678899&dopt=Abstract
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Language and number in Down syndrome: the complex developmental trajectory from infancy to adulthood. Author(s): Paterson S. Source: Downs Syndr Res Pract. 2001 October; 7(2): 79-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721533&dopt=Abstract
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Language in ageing persons with Down syndrome. Author(s): Rondal JA, Comblain A. Source: Downs Syndr Res Pract. 2002 March; 8(1): 1-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915431&dopt=Abstract
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Language skills of children and adolescents with Down syndrome: II. Production deficits. Author(s): Chapman RS, Seung HK, Schwartz SE, Kay-Raining Bird E. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 1998 August; 41(4): 861-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9712133&dopt=Abstract
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Language, cognition, and short-term memory in individuals with Down syndrome. Author(s): Chapman RS, Hesketh LJ. Source: Downs Syndr Res Pract. 2001 October; 7(1): 1-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706807&dopt=Abstract
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Laryngotracheoplasty for subglottic stenosis in Down Syndrome children: the Cincinnati experience. Author(s): Boseley ME, Link DT, Shott SR, Fitton CM, Myer CM, Cotton RT. Source: International Journal of Pediatric Otorhinolaryngology. 2001 January; 57(1): 11-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11165636&dopt=Abstract
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Late development of atrioventricular block after congenital heart surgery in down syndrome. Author(s): Banks MA, Jenson J, Kugler JD. Source: The American Journal of Cardiology. 2001 July 1; 88(1): A7, 86-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423068&dopt=Abstract
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Late diagnosis of Down syndrome due to incorrect cytogenetic diagnosis and extreme prematurity. Author(s): Druce M, Cohen IJ, Naor N, Shohat M. Source: Clinical Genetics. 1995 October; 48(4): 192-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8591670&dopt=Abstract
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Latent and congenital nystagmus in Down syndrome. Author(s): Averbuch-Heller L, Dell'Osso LF, Jacobs JB, Remler BF. Source: Journal of Neuro-Ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society. 1999 September; 19(3): 166-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10494944&dopt=Abstract
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Lateral cervical spine films in Down syndrome. Author(s): Berdon WE. Source: Pediatric Radiology. 1996 October; 26(10): 748. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9027297&dopt=Abstract
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Learning about happiness from persons with Down syndrome: feeling the sense of joy and contentment. Author(s): Robison RJ. Source: Am J Ment Retard. 2000 September; 105(5): 372-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11008845&dopt=Abstract
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Lens defects and age-related fiber cell degeneration in a mouse model of increased AbetaPP gene dosage in Down syndrome. Author(s): Frederikse PH, Ren XO. Source: American Journal of Pathology. 2002 December; 161(6): 1985-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12466113&dopt=Abstract
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Leukemia and/or myeloproliferative syndrome in neonates with Down syndrome. Author(s): Zipursky A, Brown E, Christensen H, Sutherland R, Doyle J. Source: Semin Perinatol. 1997 February; 21(1): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9190039&dopt=Abstract
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Levels of knowledge of Down syndrome and Down syndrome testing in Australian women. Author(s): Mulvey S, Wallace EM. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2001 May; 41(2): 167-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453265&dopt=Abstract
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Levels of urinary beta-core fragment, total oestriol, and the ratio of the two in secondtrimester screening for Down syndrome. Author(s): Kellner LH, Canick JA, Palomaki GE, Neveux LM, Saller DN Jr, Walker RP, Osathanondh R, Bombard AT. Source: Prenatal Diagnosis. 1997 December; 17(12): 1135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9467810&dopt=Abstract
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Lexical verb diversity in children with Down syndrome. Author(s): Grela BG. Source: Clinical Linguistics & Phonetics. 2002 June; 16(4): 251-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12148159&dopt=Abstract
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Life expectancy and social adaptation in individuals with Down syndrome with and without surgery for congenital heart disease. Author(s): Hijii T, Fukushige J, Igarashi H, Takahashi N, Ueda K. Source: Clinical Pediatrics. 1997 June; 36(6): 327-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9196231&dopt=Abstract
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Limited effectiveness of femur and humerus shortening as markers of Down syndrome in early midtrimester fetuses. Author(s): Borrell A, Costa D, Ojuel J, Martinez JM, Seres A, Margarit E, Fortuny A. Source: Fetal Diagnosis and Therapy. 1997 May-June; 12(3): 156-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9313074&dopt=Abstract
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Lineage conversion from acute lymphoblastic leukemia to acute myeloid leukemia on rearrangement of the IgH gene in a patient with Down syndrome. Author(s): Tsuboi K, Yazaki M, Miwa H, Iida S, Banno S, Wakita A, Nitta M, Ueda R. Source: International Journal of Hematology. 2002 July; 76(1): 69-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12138899&dopt=Abstract
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Linguistic and cognitive ability of adults with Down syndrome and mental retardation of unknown etiology. Author(s): Kernan KT, Sabsay S. Source: Journal of Communication Disorders. 1996 September-October; 29(5): 401-21; Quiz 422. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8938505&dopt=Abstract
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Localization of 102 exons to a 2.5 Mb region involved in Down syndrome. Author(s): Lucente D, Chen HM, Shea D, Samec SN, Rutter M, Chrast R, Rossier C, Buckler A, Antonarakis SE, McCormick MK. Source: Human Molecular Genetics. 1995 August; 4(8): 1305-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7581367&dopt=Abstract
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Localized elastosis perforans serpiginosa in a boy with Down syndrome. Author(s): Siragusa M, Romano C, Cavallari V, Schepis C. Source: Pediatric Dermatology. 1997 May-June; 14(3): 244-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9192425&dopt=Abstract
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Long term safety and efficacy of donepezil in the treatment of dementia in Alzheimer's disease in adults with Down syndrome: open label study. Author(s): Prasher VP, Adams C, Holder R; Down Syndrome Research Group. Source: International Journal of Geriatric Psychiatry. 2003 June; 18(6): 549-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12789681&dopt=Abstract
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Longevity of a woman with Down syndrome: a case study. Author(s): Chicoine B, McGuire D. Source: Mental Retardation. 1997 December; 35(6): 477-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9425879&dopt=Abstract
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Longitudinal changes in adaptive behavior in adults with Down syndrome: interim findings from a longitudinal study. Author(s): Prasher VP, Chung MC, Haque MS. Source: Am J Ment Retard. 1998 July; 103(1): 40-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9678229&dopt=Abstract
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Low spinal and pelvic bone mineral density among individuals with Down syndrome. Author(s): Sepulveda D, Allison DB, Gomez JE, Kreibich K, Brown RA, Pierson RN Jr, Heymsfield SB. Source: Am J Ment Retard. 1995 September; 100(2): 109-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8527107&dopt=Abstract
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Lower neonatal screening thyroxine concentrations in down syndrome newborns. Author(s): van Trotsenburg AS, Vulsma T, van Santen HM, Cheung W, de Vijlder JJ. Source: The Journal of Clinical Endocrinology and Metabolism. 2003 April; 88(4): 1512-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12679431&dopt=Abstract
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Magnetic resonance imaging of the upper airway in children with Down syndrome. Author(s): de Miguel-Diez J, Alvarez-Sala JL, Villa-Asensi JR. Source: American Journal of Respiratory and Critical Care Medicine. 2002 April 15; 165(8): 1187; Author Reply 1187. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11956066&dopt=Abstract
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Magnetic resonance imaging of the upper airway in children with Down syndrome. Author(s): Uong EC, McDonough JM, Tayag-Kier CE, Zhao H, Haselgrove J, Mahboubi S, Schwab RJ, Pack AI, Arens R. Source: American Journal of Respiratory and Critical Care Medicine. 2001 March; 163(3 Pt 1): 731-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254532&dopt=Abstract
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Major birth defects among infants with Down syndrome in Alexandria, Egypt (19952000): trends and risk factors. Author(s): Mokhtar MM, Abdel-Fattah M. Source: East Mediterr Health J. 2001 May; 7(3): 441-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12690765&dopt=Abstract
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Major complex pelvic arteriovenous malformation in a patient with Down syndrome. Author(s): Kassardjian Z, Lebret T, Mellot F, Herve JM, Barre P, Lugagne PM, Scherrer A, Botto H. Source: Urologia Internationalis. 2002; 69(2): 145-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12187047&dopt=Abstract
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Malignancies in Down syndrome. Author(s): Kusumakumary P, Vats TS, Ankathil R, Gattamaneni HR, Nair MK. Source: Indian J Pediatr. 1997 November-December; 64(6): 873-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10771932&dopt=Abstract
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Manifold reduction of moesin in fetal Down syndrome brain. Author(s): Lubec B, Weitzdoerfer R, Fountoulakis M. Source: Biochemical and Biophysical Research Communications. 2001 September 7; 286(5): 1191-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527426&dopt=Abstract
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Mastery motivation in children with Down syndrome. Author(s): Glenn S, Dayus B, Cunningham C, Horgan M. Source: Downs Syndr Res Pract. 2001 October; 7(2): 52-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721530&dopt=Abstract
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Maternal age-specific rates of Down syndrome used in serum screening are biased low. Author(s): Hook EB. Source: Prenatal Diagnosis. 2000 February; 20(2): 169. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694694&dopt=Abstract
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Maternal blood superoxide dismutase in Down syndrome. Author(s): Cuckle H, Arbuzova S. Source: Prenatal Diagnosis. 2000 April; 20(4): 354-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10740214&dopt=Abstract
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Maternal question-asking behavior to Taiwanese children with Down syndrome and with no disability. Author(s): Huang SF, Oi M. Source: Psychological Reports. 2001 April; 88(2): 501-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11351898&dopt=Abstract
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Maternal question-asking of Japanese children with Down syndrome and with no disability. Author(s): Huang SF, Oi M. Source: Psychological Reports. 2001 June; 88(3 Pt 2): 1096-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11597058&dopt=Abstract
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Maternal serum activin A and follistatin levels in pregnancies with Down syndrome. Author(s): Cuckle HS, Sehmi I, Jones R, Evans LW. Source: Prenatal Diagnosis. 1999 June; 19(6): 513-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10416964&dopt=Abstract
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Maternal serum beta-hCG levels in screening for Down syndrome are higher in singleton pregnancies achieved with ovulation induction and intrauterine insemination than in spontaneous singleton pregnancies. Author(s): Raty R, Virtanen A, Koskinen P, Anttila L, Laitinen P, Tiitinen A, Ekblad U. Source: Fertility and Sterility. 2001 November; 76(5): 1075-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704143&dopt=Abstract
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Maternal serum hyaluronic acid is ineffective for Down syndrome screening. Author(s): Muller F, Rebiffe M, Faina S, Vignal P. Source: Prenatal Diagnosis. 2000 January; 20(1): 80-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701860&dopt=Abstract
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Maternal serum hyperglycosylated human chorionic gonadotrophin (HhCG) in the first trimester of pregnancies affected by Down syndrome, using a sialic acid-specific lectin immunoassay. Author(s): Spencer K, Talbot JA, Abushoufa RA. Source: Prenatal Diagnosis. 2002 August; 22(8): 656-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210572&dopt=Abstract
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Maternal serum prostate-specific antigen and Down syndrome in the first and second trimesters of pregnancy. International Prenatal Screening Research Group. Author(s): Wald NJ, Hackshaw AK, Diamandis EP, Melegos DN. Source: Prenatal Diagnosis. 1999 July; 19(7): 674-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10419619&dopt=Abstract
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Maternal serum s100b protein is ineffective for Down syndrome screening. Author(s): Muller F, Ngo S, Rebiffe M, Oury JF, Uzan S, Satge D. Source: Prenatal Diagnosis. 1999 November; 19(11): 1086. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589070&dopt=Abstract
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Maternal serum screening for down syndrome by using alpha-fetoprotein and human chorionic gonadotropin in an asian population. a prospective study. Author(s): Jou HJ, Shyu MK, Chen SM, Shih JC, Hsu JJ, Hsieh FJ. Source: Fetal Diagnosis and Therapy. 2000 March-April; 15(2): 108-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10720876&dopt=Abstract
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Maternal serum screening for Down syndrome in a teaching hospital in Hong Kong. Author(s): Law L, Lau T, Fung T, Rogers MS, Hjelm M. Source: Chin Med J (Engl). 1999 August; 112(8): 754-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11601289&dopt=Abstract
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Maternal serum screening for down syndrome in pregnancies conceived by intrauterine insemination. Author(s): Hsu TY, Ou CY, Hsu JJ, Kung FT, Chang SY, Soong YK. Source: Prenatal Diagnosis. 1999 November; 19(11): 1012-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589050&dopt=Abstract
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Maternal serum screening for Down syndrome: a survey of pregnant women's views. Author(s): Paravic J, Brajenovic-Milic B, Tislaric D, Kapovic M, Botica A, Jurcan V, Milotti S. Source: Community Genetics. 1999; 2(2-3): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11789548&dopt=Abstract
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Maternal serum screening for Down syndrome--opinions on acceptance from Swedish women. Author(s): Crang-Svalenius E, Dykes AK, Jorgensen C. Source: Scandinavian Journal of Caring Sciences. 2003 March; 17(1): 30-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12581292&dopt=Abstract
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Maternal serum superoxide dismutase (SOD): a possible marker for screening Down syndrome affected pregnancies. Author(s): Ognibene A, Ciuti R, Tozzi P, Messeri G. Source: Prenatal Diagnosis. 1999 November; 19(11): 1058-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589060&dopt=Abstract
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Maternal serum urea resistant alkaline phosphatase in Down syndrome pregnancy. Author(s): Grozdea J, De La Farge F, Bourrouillou G, Calot M, Cambus JP, Valdiguie P. Source: Early Human Development. 2002 April; 67(1-2): 55-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11893436&dopt=Abstract
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Maternal smoking: age distribution, levels of alpha-fetoprotein and human chorionic gonadotrophin, and effect on detection of Down syndrome pregnancies in secondtrimester screening. Author(s): Crossley JA, Aitken DA, Waugh SM, Kelly T, Connor JM. Source: Prenatal Diagnosis. 2002 March; 22(3): 247-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920904&dopt=Abstract
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Maxillary canine-to-first premolar bilateral transposition in a female with Down syndrome. A case report. Author(s): Al-Mutawa SA, Shyama M, Honkala E. Source: Medical Principles and Practice : International Journal of the Kuwait University, Health Science Centre. 2003 July-September; 12(3): 193-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766340&dopt=Abstract
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Measurement of nasal bone length at 11-14 weeks of pregnancy and its potential role in Down syndrome risk assessment. Author(s): Orlandi F, Bilardo CM, Campogrande M, Krantz D, Hallahan T, Rossi C, Viora E. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 July; 22(1): 36-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12858300&dopt=Abstract
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Measurement of range of motion in individuals with mental retardation and with or without Down syndrome. Author(s): Angelopoulou N, Tsimaras V, Christoulas K, Mandroukas K. Source: Percept Mot Skills. 1999 October; 89(2): 550-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10597591&dopt=Abstract
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Measuring serum markers once or twice in each assay in antenatal screening for Down syndrome and neural tube defects. Author(s): Hackshaw AK, Wald NJ, George LM. Source: Prenatal Diagnosis. 2001 January; 21(1): 72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180247&dopt=Abstract
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Medical aspects of school-aged children with Down syndrome. Author(s): Leonard S, Bower C, Petterson B, Leonard H. Source: Developmental Medicine and Child Neurology. 1999 October; 41(10): 683-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10587045&dopt=Abstract
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Medical care and monitoring for the adolescent with Down syndrome. Author(s): Roizen NJ. Source: Adolescent Medicine (Philadelphia, Pa.). 2002 June; 13(2): 345-58, Vii. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986041&dopt=Abstract
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Memory training for children with Down syndrome. Author(s): Conners FA, Rosenquist CJ, Taylor LA. Source: Downs Syndr Res Pract. 2001 October; 7(1): 25-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706809&dopt=Abstract
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Mental retardation in Down syndrome: a hydrogen sulfide hpothesis. Author(s): Kamoun P. Source: Medical Hypotheses. 2001 September; 57(3): 389-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11516234&dopt=Abstract
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Methylenetetrahydrofolate reductase polymorphism in the etiology of Down syndrome. Author(s): Chadefaux-Vekemans B, Coude M, Muller F, Oury JF, Chabli A, Jais J, Kamoun P. Source: Pediatric Research. 2002 June; 51(6): 766-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032275&dopt=Abstract
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Mice trisomic for a bacterial artificial chromosome with the single-minded 2 gene (Sim2) show phenotypes similar to some of those present in the partial trisomy 16 mouse models of Down syndrome. Author(s): Chrast R, Scott HS, Madani R, Huber L, Wolfer DP, Prinz M, Aguzzi A, Lipp HP, Antonarakis SE. Source: Human Molecular Genetics. 2000 July 22; 9(12): 1853-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10915774&dopt=Abstract
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Midline developmental anomalies in Down syndrome. Author(s): Kieslich M, Fuchs S, Vlaho S, Maisch U, Boehles H. Source: Journal of Child Neurology. 2002 June; 17(6): 460-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12174971&dopt=Abstract
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Milia-like idiopathic calcinosis cutis in a patient with translocation Down syndrome. Author(s): Kotsuji T, Imakado S, Iwasaki N, Fujisawa H, Otsuka F. Source: Journal of the American Academy of Dermatology. 2001 July; 45(1): 152-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11423857&dopt=Abstract
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Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype. Author(s): Barbi G, Kennerknecht I, Wohr G, Avramopoulos D, Karadima G, Petersen MB. Source: American Journal of Medical Genetics. 2000 March 13; 91(2): 116-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10748409&dopt=Abstract
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Molecular abnormalities of the brain in Down syndrome: relevance to Alzheimer's neurodegeneration. Author(s): de la Monte SM. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 1-19. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666665&dopt=Abstract
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Molecular changes in fetal Down syndrome brain. Author(s): Engidawork E, Lubec G. Source: Journal of Neurochemistry. 2003 March; 84(5): 895-904. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12603815&dopt=Abstract
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Molecular cloning and characterization of a gene expressed in mouse developing tongue, mDscr5 gene, a homolog of human DSCR5 (Down syndrome Critical Region gene 5). Author(s): Choi DK, Suzuki Y, Yoshimura S, Togashi T, Hida M, Taylor TD, Wang Y, Sugano S, Hattori M, Sakaki Y. Source: Mammalian Genome : Official Journal of the International Mammalian Genome Society. 2001 May; 12(5): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11331941&dopt=Abstract
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Molecular dating of senile plaques in the brains of individuals with Down syndrome and in aged dogs. Author(s): Azizeh BY, Head E, Ibrahim MA, Torp R, Tenner AJ, Kim RC, Lott IT, Cotman CW. Source: Experimental Neurology. 2000 May; 163(1): 111-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10785449&dopt=Abstract
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Molecular misreading of genes in Down syndrome as a model for the Alzheimer type of neurodegeneration. Author(s): van Leeuwen FW, Hol EM. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 137-59. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666673&dopt=Abstract
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Molecular weight forms of inhibin A, inhibin B and pro-alphaC in maternal serum, amniotic fluid and placental extracts of normal and Down syndrome pregnancies. Author(s): Thirunavukarasu PP, Lambert-Messerlian G, Robertson DM, Dawson G, Canick J, Wallace EM. Source: Prenatal Diagnosis. 2002 December; 22(12): 1086-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12454963&dopt=Abstract
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Morgagni hernia with Down syndrome: a rare association -- case report and review of literature. Author(s): Parmar RC, Tullu MS, Bavdekar SB, Borwankar SS. Source: Journal of Postgraduate Medicine. 2001 July-September; 47(3): 188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11832621&dopt=Abstract
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Morphological and biochemical assessment of DNA damage and apoptosis in Down syndrome and Alzheimer disease, and effect of postmortem tissue archival on TUNEL. Author(s): Anderson AJ, Stoltzner S, Lai F, Su J, Nixon RA. Source: Neurobiology of Aging. 2000 July-August; 21(4): 511-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10924764&dopt=Abstract
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Morphometric variables of the primary second molar in children with Down syndrome. Author(s): Peretz B, Katzenel V, Shapira J. Source: J Clin Pediatr Dent. 1999 Summer; 23(4): 333-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10551134&dopt=Abstract
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Mortality and cancer incidence among individuals with Down syndrome. Author(s): Hill DA, Gridley G, Cnattingius S, Mellemkjaer L, Linet M, Adami HO, Olsen JH, Nyren O, Fraumeni JF Jr. Source: Archives of Internal Medicine. 2003 March 24; 163(6): 705-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12639204&dopt=Abstract
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Mosaicism in a patient with Down syndrome reveals post-fertilization formation of a Robertsonian translocation and isochromosome. Author(s): Bandyopadhyay R, McCaskill C, Knox-Du Bois C, Zhou Y, Berend SA, Bijlsma E, Shaffer LG. Source: American Journal of Medical Genetics. 2003 January 15; 116A(2): 159-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494435&dopt=Abstract
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Mothers and fathers of children with Down syndrome: parental stress and involvement in childcare. Author(s): Roach MA, Orsmond GI, Barratt MS. Source: Am J Ment Retard. 1999 September; 104(5): 422-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10541413&dopt=Abstract
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Motivation and learning styles in young children with Down syndrome. Author(s): Wishart J. Source: Downs Syndr Res Pract. 2001 October; 7(2): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721529&dopt=Abstract
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Motor and perceptual-motor competence in children with Down syndrome: variation in performance with age. Author(s): Spano M, Mercuri E, Rando T, Panto T, Gagliano A, Henderson S, Guzzetta F. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 1999; 3(1): 7-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10727186&dopt=Abstract
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Moyamoya disease and Down syndrome: case report and review of the literature. Author(s): de Borchgrave V, Saussu F, Depre A, de Barsy T. Source: Acta Neurol Belg. 2002 June; 102(2): 63-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12161901&dopt=Abstract
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Moyamoya syndrome in a child with Down syndrome. Author(s): Fung CW, Kwong KL, Tsui EY, Wong SN. Source: Hong Kong Medical Journal = Xianggang Yi Xue Za Zhi / Hong Kong Academy of Medicine. 2003 February; 9(1): 63-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547961&dopt=Abstract
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MTRR and MTHFR polymorphism: link to Down syndrome? Author(s): O'Leary VB, Parle-McDermott A, Molloy AM, Kirke PN, Johnson Z, Conley M, Scott JM, Mills JL. Source: American Journal of Medical Genetics. 2002 January 15; 107(2): 151-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807890&dopt=Abstract
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Multiple marker screening for Down syndrome--whom should we screen? Author(s): Cate S, Ball S. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 1999 September-October; 12(5): 367-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534085&dopt=Abstract
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Murine models for Down syndrome. Author(s): Dierssen M, Fillat C, Crnic L, Arbones M, Florez J, Estivill X. Source: Physiology & Behavior. 2001 August; 73(5): 859-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11566219&dopt=Abstract
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Musculoskeletal problems in Down Syndrome European Paediatric Orthopaedic Society Survey: the Israeli sample. Author(s): Merrick J, Ezra E, Josef B, Hendel D, Steinberg DM, Wientroub S. Source: Journal of Pediatric Orthopaedics. Part B / European Paediatric Orthopaedic Society, Pediatric Orthopaedic Society of North America. 2000 June; 9(3): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10904905&dopt=Abstract
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Mutagenesis of GATA1 is an initiating event in Down syndrome leukemogenesis. Author(s): Mundschau G, Gurbuxani S, Gamis AS, Greene ME, Arceci RJ, Crispino JD. Source: Blood. 2003 June 1; 101(11): 4298-300. Epub 2003 January 30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560215&dopt=Abstract
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Mutation of the AML1/RUNX1 gene in a transient myeloproliferative disorder patient with Down syndrome. Author(s): Taketani T, Taki T, Takita J, Ono R, Horikoshi Y, Kaneko Y, Sako M, Hanada R, Hongo T, Hayashi Y. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2002 September; 16(9): 1866-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12200707&dopt=Abstract
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Narcolepsy-like symptoms in a patient with down syndrome and without obstructive sleep apnea. Author(s): Dominguez-Ortega L, Salin-Pascual RJ, Diaz-Gallego E. Source: Sleep. 2003 May 1; 26(3): 285-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749546&dopt=Abstract
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Nasal bone evaluation in fetuses with Down syndrome during the second and third trimesters of pregnancy. Author(s): Lee W, DeVore GR, Comstock CH, Kalache KD, McNie B, Chaiworapongsa T, Conoscenti G, Treadwell MC, Johnson A, Huang R, Romero R. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2003 January; 22(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12523611&dopt=Abstract
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Nasal ciliary function and ultrastructure in Down syndrome. Author(s): Piatti G, Allegra L, Ambrosetti U, De Santi MM. Source: The Laryngoscope. 2001 July; 111(7): 1227-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568545&dopt=Abstract
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Natural family planning and Down syndrome--matching and confounding in a case control study. Author(s): Pelz J. Source: American Journal of Medical Genetics. 1996 December 18; 66(3): 363-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8985501&dopt=Abstract
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Neck flexion and extension in children with Down syndrome: a somatosensory study. Author(s): Abramson PJ, Todd NW, Holt PJ, Allen AT, Hayden GB. Source: The Laryngoscope. 1995 November; 105(11): 1209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7475877&dopt=Abstract
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Neonatal ECG screening for congenital heart disease in Down syndrome. Author(s): Narchi H. Source: Annals of Tropical Paediatrics. 1999 March; 19(1): 51-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10605520&dopt=Abstract
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Neonatal haemochromatosis associated with Down syndrome. Author(s): Cheung PC, Ng WF, Chan AK. Source: Journal of Paediatrics and Child Health. 1995 June; 31(3): 249-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7669389&dopt=Abstract
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Neurodevelopmental profile of Down syndrome in Chinese children. Author(s): Kwong KL, Wong V. Source: Journal of Paediatrics and Child Health. 1996 April; 32(2): 153-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9156526&dopt=Abstract
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Neuroendocrine-specific protein C, a marker of neuronal differentiation, is reduced in brain of patients with Down syndrome and Alzheimer's disease. Author(s): Kim SH, Yoo BC, Broers JL, Cairns N, Lubec G. Source: Biochemical and Biophysical Research Communications. 2000 September 16; 276(1): 329-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11006125&dopt=Abstract
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Neurofilament proteins NF-L, NF-M and NF-H in brain of patients with Down syndrome and Alzheimer's disease. Author(s): Bajo M, Yoo BC, Cairns N, Gratzer M, Lubec G. Source: Amino Acids. 2001; 21(3): 293-301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11764410&dopt=Abstract
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Neurological changes and emotional functioning in adults with Down Syndrome. Author(s): Nelson LD, Orme D, Osann K, Lott IT. Source: Journal of Intellectual Disability Research : Jidr. 2001 October; 45(Pt 5): 450-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11679050&dopt=Abstract
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Neuronal apoptosis inhibitory protein (NAIP)-like immunoreactivity in brains of adult patients with Down syndrome. Author(s): Seidl R, Bajo M, Bohm K, LaCasse EC, MacKenzie AE, Cairns N, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 283-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666683&dopt=Abstract
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Neuronal loss and beta-amyloid removal in the amygdala of people with Down syndrome. Author(s): Wegiel J, Wisniewski HM, Morys J, Tarnawski M, Kuchna I, Dziewiatkowski J, Pirttila T, Krivimaki T, Lehtimaki T, Lach B. Source: Neurobiology of Aging. 1999 May-June; 20(3): 259-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10588573&dopt=Abstract
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Neuronal oxidative stress precedes amyloid-beta deposition in Down syndrome. Author(s): Nunomura A, Perry G, Pappolla MA, Friedland RP, Hirai K, Chiba S, Smith MA. Source: Journal of Neuropathology and Experimental Neurology. 2000 November; 59(11): 1011-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11089579&dopt=Abstract
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Neutrophil chemotaxis in Down syndrome and normal children to Actinobacillus actinomycetemcomitans. Author(s): Sreedevi H, Munshi AK. Source: J Clin Pediatr Dent. 1998 Winter; 22(2): 141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9643189&dopt=Abstract
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New Down syndrome screening algorithm: ultrasonographic biometry and multiple serum markers combined with maternal age. Author(s): Bahado-Singh RO, Oz AU, Kovanci E, Deren O, Copel J, Baumgarten A, Mahoney J. Source: American Journal of Obstetrics and Gynecology. 1998 December; 179(6 Pt 1): 1627-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9855608&dopt=Abstract
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New estimates of Down syndrome risks at chorionic villus sampling, amniocentesis, and livebirth in women of advanced maternal age from a uniquely defined population. Author(s): Halliday JL, Watson LF, Lumley J, Danks DM, Sheffield LJ. Source: Prenatal Diagnosis. 1995 May; 15(5): 455-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7644436&dopt=Abstract
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New triple screen test for Down syndrome: combined urine analytes and serum AFP. Author(s): Bahado-Singh RO, Oz U, Kovanci E, Cermik D, Flores D, Copel J, Mahoney M, Cole L. Source: The Journal of Maternal-Fetal Medicine. 1998 May-June; 7(3): 111-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9642606&dopt=Abstract
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Nicked free beta-subunit and Down syndrome screening. Author(s): Palomaki GE, Haddow JE. Source: American Journal of Obstetrics and Gynecology. 1996 October; 175(4 Pt 1): 1075. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885779&dopt=Abstract
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Nicked free beta-subunit of human chorionic gonadotropin: a potential new marker for Down syndrome screening. Author(s): Rotmensch S, Liberati M, Kardana A, Copel JA, Ben-Rafael Z, Cole LA. Source: American Journal of Obstetrics and Gynecology. 1996 February; 174(2): 609-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8623792&dopt=Abstract
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No evidence for genomic imprinting in liver-born Down syndrome patients. Author(s): Stoll C, Alembik Y, Dott B, Feingold J. Source: Acta Genet Med Gemellol (Roma). 1996; 45(1-2): 265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8872044&dopt=Abstract
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Noninvasive means of identifying fetuses with possible Down syndrome: a review. Author(s): Kubas C. Source: The Journal of Perinatal & Neonatal Nursing. 1999 September; 13(2): 27-46. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10818852&dopt=Abstract
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Nonketotic hyperosmolar diabetic coma in an infant with Down syndrome. Author(s): Green DA. Source: Clinical Pediatrics. 1999 May; 38(5): 317-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10349534&dopt=Abstract
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Nonverbal communication and early language acquisition in children with Down syndrome and in normally developing children. Author(s): Mundy P, Kasari C, Sigman M, Ruskin E. Source: Journal of Speech and Hearing Research. 1995 February; 38(1): 157-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7537345&dopt=Abstract
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Normal nuchal thickness in the midtrimester indicates reduced risk of Down syndrome in pregnancies with abnormal triple-screen results. Author(s): Bahado-Singh RO, Goldstein I, Uerpairojkit B, Copel JA, Mahoney MJ, Baumgarten A. Source: American Journal of Obstetrics and Gynecology. 1995 October; 173(4): 1106-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485301&dopt=Abstract
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Novel word acquisition in children with Down syndrome: does modality make a difference? Author(s): Bird EK, Gaskell A, Babineau MD, Macdonald S. Source: Journal of Communication Disorders. 2000 May-June; 33(3): 241-65; Quiz 265-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10907718&dopt=Abstract
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Nuchal index: a gestational age independent ultrasound marker for the detection of Down syndrome. Author(s): Lim KI, Pugash D, Dansereau J, Wilson RD. Source: Prenatal Diagnosis. 2002 December; 22(13): 1233-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478640&dopt=Abstract
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Nuchal thickness, urine beta-core fragment level, and maternal age for down syndrome screening. Author(s): Bahado-Singh RO, Oz AU, Flores D, Cermik D, Acuna E, Mahoney MJ, Cole L. Source: American Journal of Obstetrics and Gynecology. 1999 February; 180(2 Pt 1): 4915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9988824&dopt=Abstract
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Nuchal translucency and first trimester biochemical markers for down syndrome screening: a cost-effectiveness analysis. Author(s): Caughey AB, Kuppermann M, Norton ME, Washington AE. Source: American Journal of Obstetrics and Gynecology. 2002 November; 187(5): 123945. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12439512&dopt=Abstract
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Nucleolus organizer region heteromorphism in patients with Down syndrome and their parents. Author(s): Nazmy NA, Kotb SM, Mokhtar MM, Ismail SR. Source: East Mediterr Health J. 1999 March; 5(2): 299-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793806&dopt=Abstract
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Nutrient intake and obesity in prepubescent children with Down syndrome. Author(s): Luke A, Sutton M, Schoeller DA, Roizen NJ. Source: Journal of the American Dietetic Association. 1996 December; 96(12): 1262-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8948387&dopt=Abstract
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Nutritional rickets in a child with Down syndrome. Author(s): Cabana MD, Capone G, Fritz A, Berkovitz G. Source: Clinical Pediatrics. 1997 April; 36(4): 235-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9114996&dopt=Abstract
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Observational learning in children with Down syndrome and developmental delays: the effect of presentation speed in videotaped modelling. Author(s): Biederman GB, Stepaniuk S, Davey VA, Raven K, Ahn D. Source: Downs Syndr Res Pract. 1999 August; 6(1): 12-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890243&dopt=Abstract
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Occipitoatlantal and occipitoaxial hypermobility in Down syndrome. Author(s): Uno K, Kataoka O, Shiba R. Source: Spine. 1996 June 15; 21(12): 1430-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8792519&dopt=Abstract
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Occipitocervical fusion by Luque loop rod instrumentation in Down syndrome. Author(s): Higo M, Sakou T, Taketomi E, Kojyo T. Source: Journal of Pediatric Orthopedics. 1995 July-August; 15(4): 539-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7560051&dopt=Abstract
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Occiput-cervical fusion for symptomatic atlantoaxial subluxation in a 32-month-old child with Down syndrome: a case report. Author(s): Tseng SH, Cheng Y. Source: Spinal Cord : the Official Journal of the International Medical Society of Paraplegia. 1998 July; 36(7): 520-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9670390&dopt=Abstract
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Occlusion of unilateral carotid artery in Down syndrome. Author(s): Gaggero R, Donati PT, Curia R, De Negri M. Source: Brain & Development. 1996 January-February; 18(1): 81-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8907351&dopt=Abstract
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Ocular abnormalities in Down syndrome: an analysis of 140 Chinese children. Author(s): Wong V, Ho D. Source: Pediatric Neurology. 1997 May; 16(4): 311-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9258964&dopt=Abstract
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Ocular manifestations in Down syndrome. Author(s): Davis JS. Source: Pa Med. 1996 March; 99 Suppl: 67-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8866999&dopt=Abstract
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Oesophageal atresia and Down syndrome. Author(s): Bianca S, Bianca M, Ettore G. Source: Downs Syndr Res Pract. 2002 March; 8(1): 29-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915435&dopt=Abstract
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Olfactory impairment increases as a function of age in persons with Down syndrome. Author(s): Nijjar RK, Murphy C. Source: Neurobiology of Aging. 2002 January-February; 23(1): 65-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11755021&dopt=Abstract
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Oligodontia: a radiographic comparison of subjects with Down syndrome and normal subjects. Author(s): Kumasaka S, Miyagi A, Sakai N, Shindo J, Kashima I. Source: Spec Care Dentist. 1997 July-August; 17(4): 137-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9791293&dopt=Abstract
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Oligosaccharide variants of hCG-related molecules: potential screening markers for Down syndrome. Author(s): Cole LA, Cermik D, Bahado-Singh R. Source: Prenatal Diagnosis. 1997 December; 17(12): 1188-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9467819&dopt=Abstract
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On chronological changes in the basic EEG rhythm in persons with Down syndrome with special reference to slowing of alpha waves. Author(s): Katada A, Hasegawa S, Ohira D, Kumagai T, Harashima T, Ozaki H, Suzuki H. Source: Brain & Development. 2000 June; 22(4): 224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10838108&dopt=Abstract
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On the cause of mental retardation in Down syndrome: extrapolation from full and segmental trisomy 16 mouse models. Author(s): Galdzicki Z, Siarey R, Pearce R, Stoll J, Rapoport SI. Source: Brain Research. Brain Research Reviews. 2001 April; 35(2): 115-45. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11336779&dopt=Abstract
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Ongoing surveillance for neural tube defects and Down syndrome in a large urban maternal newborn hospital. Author(s): Wyatt PR, Summers AM, Dimnik G, Pollard B, Shilletto N. Source: Annals of the New York Academy of Sciences. 1998 June 18; 847: 252-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9668722&dopt=Abstract
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Onset of speech-like vocalizations in infants with Down syndrome. Author(s): Lynch MP, Oller DK, Steffens ML, Levine SL, Basinger DL, Umbel V. Source: Am J Ment Retard. 1995 July; 100(1): 68-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7546639&dopt=Abstract
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Optic disc elevation in Down syndrome. Author(s): Al-Hemidan AI, Al-Hazzaa SA, Chavis P, Al-Hussein H. Source: Ophthalmic Genetics. 1999 March; 20(1): 45-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10415465&dopt=Abstract
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Optic nerve coloboma in Down syndrome. Author(s): De Souza CF, Berbigier GA, Costa F, Ruschel SP, Silva T, Schuler L. Source: Clinical Dysmorphology. 1995 April; 4(2): 176-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7606327&dopt=Abstract
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Optimal care for children with Down syndrome in India. Author(s): Verma IC, Kabra M, Gangakhedkar AK. Source: Indian J Pediatr. 1996 January-February; 63(1): 121-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10829977&dopt=Abstract
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Oral hygiene, gingivitis, and periodontitis in persons with Down syndrome. Author(s): Lopez-Perez R, Borges-Yanez SA, Jimenez-Garcia G, Maupome G. Source: Spec Care Dentist. 2002 November-December; 22(6): 214-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790229&dopt=Abstract
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Organization of a simple two-joint synergy in individuals with Down syndrome. Author(s): Aruin AS, Almeida GL, Latash ML. Source: Am J Ment Retard. 1996 November; 101(3): 256-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8933900&dopt=Abstract
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Origin of trisomy 21 in Down syndrome cases from a Spanish population registry. Author(s): Gomez D, Solsona E, Guitart M, Baena N, Gabau E, Egozcue J, Caballin MR. Source: Annales De Genetique. 2000 January-March; 43(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10818217&dopt=Abstract
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Orthodontic considerations in individuals with Down syndrome: a case report. Author(s): Desai SS, Flanagan TJ. Source: Angle Orthod. 1999 February; 69(1): 85-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10022190&dopt=Abstract
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Otolaryngologic manifestations of Down syndrome. Author(s): Kanamori G, Witter M, Brown J, Williams-Smith L. Source: Otolaryngologic Clinics of North America. 2000 December; 33(6): 1285-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449787&dopt=Abstract
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Outcome validation of the Beckman Coulter access analyzer in a second-trimester Down syndrome serum screening application. Author(s): MacRae AR, Gardner HA, Allen LC, Tokmakejian S, Lepage N. Source: Clinical Chemistry. 2003 January; 49(1): 69-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12507962&dopt=Abstract
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Overexpression of bcl-2 in transient abnormal myelopoiesis associated with Down syndrome. Author(s): Yoshioka K, Yamamoto S, Moriguchi N, Miyata H, Tsukiyama K, Isokawa S, Horiuchi F, Takemura T. Source: Annals of Hematology. 2000 June; 79(6): 319-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10901611&dopt=Abstract
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Overexpression of DNAse I in brain of patients with Down syndrome. Author(s): Schatzmann-Turhani D, Labudova O, Yeghiazaryan K, Rink H, Hauser E, Cairns N, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 353-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666689&dopt=Abstract
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Overexpression of FABP7 in Down syndrome fetal brains is associated with PKNOX1 gene-dosage imbalance. Author(s): Sanchez-Font MF, Bosch-Comas A, Gonzalez-Duarte R, Marfany G. Source: Nucleic Acids Research. 2003 June 1; 31(11): 2769-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771203&dopt=Abstract
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Overweight prevalence in persons with Down syndrome. Author(s): Rubin SS, Rimmer JH, Chicoine B, Braddock D, McGuire DE. Source: Mental Retardation. 1998 June; 36(3): 175-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9638037&dopt=Abstract
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Oxidation of Abeta and plaque biogenesis in Alzheimer's disease and Down syndrome. Author(s): Head E, Garzon-Rodriguez W, Johnson JK, Lott IT, Cotman CW, Glabe C. Source: Neurobiology of Disease. 2001 October; 8(5): 792-806. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11592849&dopt=Abstract
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Oxidative stress and neural dysfunction in Down syndrome. Author(s): Iannello RC, Crack PJ, de Haan JB, Kola I. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 257-67. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666681&dopt=Abstract
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Oxidative stress in Portuguese children with Down syndrome. Author(s): Pinto M, Neves J, Palha M, Bicho M. Source: Downs Syndr Res Pract. 2002 September; 8(2): 79-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407973&dopt=Abstract
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Palate vault morphology in Down syndrome. Author(s): Panchon-Ruiz A, Jornet-Carrillo V, Sanchez del Campo F. Source: Journal of Craniofacial Genetics and Developmental Biology. 2000 OctoberDecember; 20(4): 198-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11354516&dopt=Abstract
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Parallels of craniofacial maldevelopment in Down syndrome and Ts65Dn mice. Author(s): Richtsmeier JT, Baxter LL, Reeves RH. Source: Developmental Dynamics : an Official Publication of the American Association of Anatomists. 2000 February; 217(2): 137-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10706138&dopt=Abstract
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Paravertebral neoplasm in a child with Down syndrome (DS). Author(s): Satge D, Rubie H, Sommelet D. Source: Pediatric Surgery International. 2001 March; 17(2-3): 251. Corrected and Republished In: http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315308&dopt=Abstract
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Parent of a child with Down syndrome. Author(s): Carey JC. Source: American Journal of Medical Genetics. 2002 May 1; 109(3): 241. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11977187&dopt=Abstract
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Parental age and the origin of extra chromosome 21 in Down syndrome. Author(s): Jyothy A, Kumar KS, Mallikarjuna GN, Babu Rao V, Uma Devi B, Sujatha M, Reddy PP. Source: Journal of Human Genetics. 2001; 46(6): 347-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11393539&dopt=Abstract
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Parental opinions about facial plastic surgery for individuals with down syndrome. Author(s): Goeke J, Kassow D, May D, Kundert D. Source: Mental Retardation. 2003 February; 41(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12597721&dopt=Abstract
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Parental perspectives on inclusion: effects of autism and Down syndrome. Author(s): Kasari C, Freeman SF, Bauminger N, Alkin MC. Source: Journal of Autism and Developmental Disorders. 1999 August; 29(4): 297-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10478729&dopt=Abstract
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Parental reports of spoken language skills in children with Down syndrome. Author(s): Berglund E, Eriksson M, Johansson I. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 2001 February; 44(1): 179-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11218101&dopt=Abstract
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Parent-offspring resemblance of palmar and plantar dermatoglyphic patterns in Down syndrome. Author(s): Langenbeck U, Herzberger G, Kummerle S. Source: Cytogenetics and Cell Genetics. 2000; 91(1-4): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173849&dopt=Abstract
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Parents' reports of young people with Down syndrome talking out loud to themselves. Author(s): Glenn SM, Cunningham CC. Source: Mental Retardation. 2000 December; 38(6): 498-505. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126073&dopt=Abstract
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Participation in maternal serum screening for Down syndrome, neural tube defects, and trisomy 18 following screen-positive results in a previous pregnancy. Author(s): Rausch DN, Lambert-Messerlian GM, Canick JA. Source: The Western Journal of Medicine. 2000 September; 173(3): 180-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10986181&dopt=Abstract
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Paternal isodisomy 7q secondary to monosomy 7 at recurrence in a Down syndrome child with acute myelogenous leukemia. Author(s): Picos-Cardenas VJ, Meza-Espinoza JP, Gutierrez-Angulo M, Esparza-Flores MA, Ayala-Madrigal ML, Hansmann I, Gonzalez GJ. Source: Cancer Genetics and Cytogenetics. 2002 April 15; 134(2): 138-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12034527&dopt=Abstract
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Pathologic quiz case: nonimmune hydrops in a newborn. Down syndrome with acute (transient) leukemia. Author(s): Oetama BK, Tucay RF, Morgan DL. Source: Archives of Pathology & Laboratory Medicine. 2001 December; 125(12): 1609-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11735703&dopt=Abstract
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Pelvic CT morphometry in Down syndrome: implications for prenatal US evaluation-preliminary results. Author(s): Freed KS, Kliewer MA, Hertzberg BS, DeLong DM, Paulson EK, Nelson RC. Source: Radiology. 2000 January; 214(1): 205-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10644125&dopt=Abstract
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Periconceptional exposure to contraceptive pills and risk for Down syndrome. Author(s): Martinez-Frias ML, Bermejo E, Rodriguez-Pinilla E, Prieto L. Source: Journal of Perinatology : Official Journal of the California Perinatal Association. 2001 July-August; 21(5): 288-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11536021&dopt=Abstract
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Perinatal growth of prefrontal layer III pyramids in Down syndrome. Author(s): Vuksic M, Petanjek Z, Rasin MR, Kostovic I. Source: Pediatric Neurology. 2002 July; 27(1): 36-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12160971&dopt=Abstract
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Periodontopathic bacteria in children with Down syndrome. Author(s): Amano A, Kishima T, Kimura S, Takiguchi M, Ooshima T, Hamada S, Morisaki I. Source: J Periodontol. 2000 February; 71(2): 249-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10711615&dopt=Abstract
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Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, is under-expressed in Down syndrome fetal brains. Author(s): Sanchez-Font MF, Sebastia J, Sanfeliu C, Cristofol R, Marfany G, GonzalezDuarte R. Source: Cellular and Molecular Life Sciences : Cmls. 2003 July; 60(7): 1513-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12943237&dopt=Abstract
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Phonological awareness and oral reading skill in children with Down syndrome. Author(s): Cupples L, Iacono T. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 2000 June; 43(3): 595608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10877431&dopt=Abstract
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Phospholipid composition and levels are altered in Down syndrome brain. Author(s): Murphy EJ, Schapiro MB, Rapoport SI, Shetty HU. Source: Brain Research. 2000 June 9; 867(1-2): 9-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10837793&dopt=Abstract
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Piracetam therapy does not enhance cognitive functioning in children with down syndrome. Author(s): Lobaugh NJ, Karaskov V, Rombough V, Rovet J, Bryson S, Greenbaum R, Haslam RH, Koren G. Source: Archives of Pediatrics & Adolescent Medicine. 2001 April; 155(4): 442-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296070&dopt=Abstract
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Piracetam therapy for Down syndrome: a rush to judgment? Author(s): Black SL. Source: Archives of Pediatrics & Adolescent Medicine. 2001 October; 155(10): 1176; Author Reply 1177-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576019&dopt=Abstract
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Plasma amyloid beta protein 1-42 levels are increased in old Down Syndrome but not in young Down Syndrome. Author(s): Mehta PD, Mehta SP, Fedor B, Patrick BA, Emmerling M, Dalton AJ. Source: Neuroscience Letters. 2003 May 22; 342(3): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12757888&dopt=Abstract
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Plasma carnitine levels in children with Down syndrome. Author(s): Seven M, Cengiz M, Tuzgen S, Iscan MY. Source: American Journal of Human Biology : the Official Journal of the Human Biology Council. 2001 November-December; 13(6): 721-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11748810&dopt=Abstract
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Plasma levels of amyloid beta 40 and 42 are independent from ApoE genotype and mental retardation in Down syndrome. Author(s): Cavani S, Tamaoka A, Moretti A, Marinelli L, Angelini G, Di Stefano S, Piombo G, Cazzulo V, Matsuno S, Shoji S, Furiya Y, Zaccheo D, Dagna-Bricarelli F, Tabaton M, Mori H. Source: American Journal of Medical Genetics. 2000 November 27; 95(3): 224-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11102927&dopt=Abstract
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Plasminogen activator inhibitor type 1 in adults with Down syndrome and protection against macrovascular disease. Author(s): Hopkins WE, Fukagawa NK, Sobel BE, Schneider DJ. Source: The American Journal of Cardiology. 2000 March 15; 85(6): 784-6, A9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000063&dopt=Abstract
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Point nucleotidic changes in both the RET proto-oncogene and the endothelin-B receptor gene in a Hirschsprung disease patient associated with Down syndrome. Author(s): Sakai T, Wakizaka A, Nirasawa Y, Ito Y. Source: The Tohoku Journal of Experimental Medicine. 1999 January; 187(1): 43-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10458491&dopt=Abstract
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Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Author(s): Hobbs CA, Sherman SL, Yi P, Hopkins SE, Torfs CP, Hine RJ, Pogribna M, Rozen R, James SJ. Source: American Journal of Human Genetics. 2000 September; 67(3): 623-30. Epub 2000 August 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10930360&dopt=Abstract
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Poor outcome in Down syndrome fetuses with cardiac anomalies or growth retardation. Author(s): Wessels MW, Los FJ, Frohn-Mulder IM, Niermeijer MF, Willems PJ, Wladimiroff JW. Source: American Journal of Medical Genetics. 2003 January 15; 116A(2): 147-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12494433&dopt=Abstract
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Posterior leukoencephalopathy syndrome during steroid therapy in a down syndrome patient with nephrotic syndrome. Author(s): Kim BS, Lee SH, Lee JE, Chung SW, Kim YO, Choi KB, Choi EJ, Bang BK. Source: Nephron. 2001 March; 87(3): 289-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11287769&dopt=Abstract
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Potential biases in Down syndrome birth prevalence estimation. Author(s): Cuckle H. Source: Journal of Medical Screening. 2002; 9(4): 192; Author Reply 192. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12518014&dopt=Abstract
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Practice variations in biochemical screening for Down syndrome. Author(s): Lenke RR, Walkowicz K, Baker K. Source: Genetic Testing. 1997-98; 1(4): 279-81; Discussion 282. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464658&dopt=Abstract
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Preconceptional intake of folate and vitamin B12 in the prevention of neural tube defects and Down syndrome. Author(s): Palekar AG. Source: American Journal of Obstetrics and Gynecology. 2001 February; 184(3): 517. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228518&dopt=Abstract
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Predicting language production in children and adolescents with Down syndrome: the role of comprehension. Author(s): Chapman RS, Seung HK, Schwartz SE, Bird EK. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 2000 April; 43(2): 340-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10757688&dopt=Abstract
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Predictive value of the triple screening test for the phenotype of Down syndrome. Author(s): Tanski S, Rosengren SS, Benn PA. Source: American Journal of Medical Genetics. 1999 July 16; 85(2): 123-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10406664&dopt=Abstract
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Preference assessment of prenatal diagnosis for Down syndrome: is 35 years a rational cutoff? Author(s): Grobman WA, Dooley SL, Welshman EE, Pergament E, Calhoun EA. Source: Prenatal Diagnosis. 2002 December; 22(13): 1195-200. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12478632&dopt=Abstract
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Pregnancy outcome in Hispanic patients with unexplained positive triple marker screening for Down syndrome. Author(s): Naylor CS, Porto M, Cohen B, Garite TJ. Source: The Journal of Maternal-Fetal Medicine. 2001 February; 10(1): 20-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11332414&dopt=Abstract
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Pregnancy outcomes of women with positive serum screening results for Down syndrome and trisomy 18. Author(s): Summers AM, Huang T, Wyatt PR. Source: Prenatal Diagnosis. 2002 March; 22(3): 269-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920909&dopt=Abstract
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Prehension in young children with Down syndrome. Author(s): Kearney K, Gentile AM. Source: Acta Psychologica. 2003 January; 112(1): 3-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12423897&dopt=Abstract
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Prenatal diagnosis and false negative result for a case of Down syndrome with normal karyotype. Author(s): Lizcano-Gil LA, Burgos K, Guarin DF. Source: Genet Couns. 2001; 12(2): 167-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11491313&dopt=Abstract
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Prenatal diagnosis of congenital leukemia in a fetus at 25 weeks' gestation with Down syndrome: case report and review of the literature. Author(s): Robertson M, De Jong G, Mansvelt E. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2003 May; 21(5): 486-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768562&dopt=Abstract
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Prenatal screening for Down syndrome: pre-analytical precautions. Author(s): Doche C, Bartoli M, Mercier S, Demiaux J, Gascht J, Dingeon B. Source: Prenatal Diagnosis. 2000 August; 20(8): 684-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951485&dopt=Abstract
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Prenatal testing and counseling for Down syndrome. Author(s): Klein J. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 May-June; 13(3): 227-8. Erratum In: J Am Board Fam Pract. 2000 November-December; 13(6): 423. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10826878&dopt=Abstract
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Prenatal ultrasonographic diagnosis of nasal bone abnormalities in three fetuses with Down syndrome. Author(s): Sonek JD, Nicolaides KH. Source: American Journal of Obstetrics and Gynecology. 2002 January; 186(1): 139-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11810099&dopt=Abstract
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Presenilin 1 and alpha-1-antichymotrypsin polymorphisms in Down syndrome: no effect on the presence of dementia. Author(s): Tyrrell J, Cosgrave M, McPherson J, Hawi Z, Trulock V, Calvert J, Lawlor B, Gill M. Source: American Journal of Medical Genetics. 1999 December 15; 88(6): 616-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10581479&dopt=Abstract
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Prevalence and clinical picture of celiac disease in italian down syndrome patients: a multicenter study. Author(s): Bonamico M, Mariani P, Danesi HM, Crisogianni M, Failla P, Gemme G, Quartino AR, Giannotti A, Castro M, Balli F, Lecora M, Andria G, Guariso G, Gabrielli O, Catassi C, Lazzari R, Balocco NA, De Virgiliis S, Culasso F, Romano C; SIGEP (Italian Society of Pediatric Gastroenterology and Hepatology) and Medical Genetic Group. Source: Journal of Pediatric Gastroenterology and Nutrition. 2001 August; 33(2): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568513&dopt=Abstract
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Prevalence of celiac disease in Down syndrome in the United States. Author(s): Zachor DA, Mroczek-Musulman E, Brown P. Source: Journal of Pediatric Gastroenterology and Nutrition. 2000 September; 31(3): 2759. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997372&dopt=Abstract
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Prevalence of Down syndrome in Glasgow, 1980-96--the growing impact of prenatal diagnosis on younger mothers. Author(s): Iliyasu Z, Gilmour WH, Stone DH. Source: Health Bull (Edinb). 2002 January; 60(1): 20-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12664764&dopt=Abstract
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Prevalence of numeric anomalies in the permanent dentition of patients with Down syndrome. Author(s): Acerbi AG, de Freitas C, de Magalhaes MH. Source: Spec Care Dentist. 2001 March-April; 21(2): 75-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11484586&dopt=Abstract
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Prevalence of oral health problems in a group of individuals with Down syndrome in France. Author(s): Hennequin M, Allison PJ, Veyrune JL. Source: Developmental Medicine and Child Neurology. 2000 October; 42(10): 691-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11085298&dopt=Abstract
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Prevalence of tooth transposition, third molar agenesis, and maxillary canine impaction in individuals with Down syndrome. Author(s): Shapira J, Chaushu S, Becker A. Source: Angle Orthod. 2000 August; 70(4): 290-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961778&dopt=Abstract
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Procedure-related miscarriages and Down syndrome-affected births: implications for prenatal testing based on women's preferences. Author(s): Kuppermann M, Nease RF, Learman LA, Gates E, Blumberg B, Washington AE. Source: Obstetrics and Gynecology. 2000 October; 96(4): 511-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11004350&dopt=Abstract
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Profiles of communication disorder in children with velocardiofacial syndrome: comparison to children with Down syndrome. Author(s): Scherer NJ, D'Antonio LL, Rodgers JR. Source: Genetics in Medicine : Official Journal of the American College of Medical Genetics. 2001 January-February; 3(1): 72-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11339384&dopt=Abstract
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Profiles of grammatical morphology and sentence imitation in children with specific language impairment and Down syndrome. Author(s): Eadie PA, Fey ME, Douglas JM, Parsons CL. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 2002 August; 45(4): 720-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12199402&dopt=Abstract
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Promoting balance and jumping skills in children with Down syndrome. Author(s): Wang WY, Ju YH. Source: Percept Mot Skills. 2002 April; 94(2): 443-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027336&dopt=Abstract
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Prospective polysomnographic analysis of obstructive sleep apnea in down syndrome. Author(s): Dyken ME, Lin-Dyken DC, Poulton S, Zimmerman MB, Sedars E. Source: Archives of Pediatrics & Adolescent Medicine. 2003 July; 157(7): 655-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860786&dopt=Abstract
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Protein expression in Down syndrome brain. Author(s): Engidawork E, Lubec G. Source: Amino Acids. 2001 December; 21(4): 331-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11858695&dopt=Abstract
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Pulmonary edema in 6 children with Down syndrome during travel to moderate altitudes. Author(s): Durmowicz AG. Source: Pediatrics. 2001 August; 108(2): 443-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11483813&dopt=Abstract
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Quality assessment in prospective nuchal translucency screening for Down syndrome. Author(s): Wojdemann KR, Christiansen M, Sundberg K, Larsen SO, Shalmi A, Tabor A. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2001 December; 18(6): 641-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844206&dopt=Abstract
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Quality of life--ageing and Down syndrome. Author(s): Brown R, Taylor J, Matthews B. Source: Downs Syndr Res Pract. 2001 July; 6(3): 111-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501212&dopt=Abstract
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Quality of written information used in Down syndrome screening. Author(s): Murray J, Cuckle H, Sehmi I, Wilson C, Ellis A. Source: Prenatal Diagnosis. 2001 February; 21(2): 138-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241543&dopt=Abstract
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Quantification of modified amyloid beta peptides in Alzheimer disease and Down syndrome brains. Author(s): Hosoda R, Saido TC, Otvos L Jr, Arai T, Mann DM, Lee VM, Trojanowski JQ, Iwatsubo T. Source: Journal of Neuropathology and Experimental Neurology. 1998 November; 57(11): 1089-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9825946&dopt=Abstract
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Quantitative analysis of senile plaques in Alzheimer disease: observation of lognormal size distribution and molecular epidemiology of differences associated with apolipoprotein E genotype and trisomy 21 (Down syndrome). Author(s): Hyman BT, West HL, Rebeck GW, Buldyrev SV, Mantegna RN, Ukleja M, Havlin S, Stanley HE. Source: Proceedings of the National Academy of Sciences of the United States of America. 1995 April 11; 92(8): 3586-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7724603&dopt=Abstract
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Raised maternal serum placenta growth factor concentration during the second trimester is associated with Down syndrome. Author(s): Su YN, Hsu JJ, Lee CN, Cheng WF, Kung CC, Hsieh FJ. Source: Prenatal Diagnosis. 2002 January; 22(1): 8-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11810642&dopt=Abstract
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Rapid prenatal diagnosis of Down syndrome using quantitative fluorescence in situ hybridization on interphase nuclei. Author(s): Truong K, Gibaud A, Dupont JM, Guilly MN, Soussaline F, Dutrillaux B, Malfoy B. Source: Prenatal Diagnosis. 2003 February; 23(2): 146-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12575023&dopt=Abstract
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Rates of Down syndrome at livebirth by one-year maternal age intervals in studies with apparent close to complete ascertainment in populations of European origin: a proposed revised rate schedule for use in genetic and prenatal screening. Author(s): Hecht CA, Hook EB. Source: American Journal of Medical Genetics. 1996 April 24; 62(4): 376-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8723068&dopt=Abstract
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Ratio of nuchal thickness to humerus length for Down syndrome detection. Author(s): Bahado-Singh RO, Oz U, Hsu CD, Deren O, Copel JA, Mahoney MJ. Source: American Journal of Obstetrics and Gynecology. 2001 May; 184(6): 1284-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11349203&dopt=Abstract
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Rational Down syndrome screening policy. Author(s): Cuckle H. Source: American Journal of Public Health. 1998 April; 88(4): 558-9. Review. Erratum In: Am J Public Health 1998 June; 88(6): 972. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9550992&dopt=Abstract
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Reactive oxygen species and their contribution to pathology in Down syndrome. Author(s): de Haan JB, Wolvetang EJ, Cristiano F, Iannello R, Bladier C, Kelner MJ, Kola I. Source: Adv Pharmacol. 1997; 38: 379-402. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8895817&dopt=Abstract
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Reading with Abby: a case study of individual tutoring with a young adult with Down syndrome. Author(s): Gallaher KM, van Kraayenoord CE, Jobling A, Moni KB. Source: Downs Syndr Res Pract. 2002 September; 8(2): 59-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407970&dopt=Abstract
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Reading, language and memory skills: a comparative longitudinal study of children with Down syndrome and their mainstream peers. Author(s): Byrne A, MacDonald J, Buckley S. Source: The British Journal of Educational Psychology. 2002 December; 72(Pt 4): 513-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495564&dopt=Abstract
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Recent advances in maternal serum screening for Down syndrome. Author(s): Messerlian GM, Canick JA. Source: Medicine and Health, Rhode Island. 2002 December; 85(12): 362-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12593353&dopt=Abstract
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Recent trends in the prevalence of Down syndrome in Japan, 1980-1997. Author(s): Hoshi N, Hattori R, Hanatani K, Okuyama K, Yamada H, Kishida T, Yamada T, Sagawa T, Sumiyoshi Y, Fujimoto S. Source: American Journal of Medical Genetics. 1999 June 4; 84(4): 340-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10340648&dopt=Abstract
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Recognition of identity and expression in faces by children with Down syndrome. Author(s): Wishart JG, Pitcairn TK. Source: Am J Ment Retard. 2000 November; 105(6): 466-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958200&dopt=Abstract
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Recombinant Down syndrome: a case report and literature review. Author(s): Lazzaro SJ, Speevak MD, Farrell SA. Source: Clinical Genetics. 2001 February; 59(2): 128-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11260215&dopt=Abstract
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Recurrent dislocation of the hip in a child with Down syndrome: a 20-year follow-up. Author(s): Gore DR. Source: J South Orthop Assoc. 1999 Spring; 8(1): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132858&dopt=Abstract
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Reduced aldehyde dehydrogenase levels in the brain of patients with Down syndrome. Author(s): Lubec G, Labudova O, Cairns N, Berndt P, Langen H, Fountoulakis M. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 21-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666666&dopt=Abstract
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Reduced inferior olivary neuron number in early Down syndrome. Author(s): Pine SS, Landing BH, Shankle WR. Source: Pediatric Pathology & Laboratory Medicine : Journal of the Society for Pediatric Pathology, Affiliated with the International Paediatric Pathology Association. 1997 JulyAugust; 17(4): 537-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9211546&dopt=Abstract
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Reduced levels of DEAD-box proteins DBP-RB and p72 in fetal Down syndrome brains. Author(s): Kircher SG, Kim SH, Fountoulakis M, Lubec G. Source: Neurochemical Research. 2002 October; 27(10): 1141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12462412&dopt=Abstract
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Reduced ovarian complement, premature ovarian failure, and Down syndrome. Author(s): Salamanca-Gomez F, Buentello L, Salamanca-Buentello F. Source: American Journal of Medical Genetics. 2001 March 1; 99(2): 168-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241483&dopt=Abstract
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Reduction of actin-related protein complex 2/3 in fetal Down syndrome brain. Author(s): Weitzdoerfer R, Fountoulakis M, Lubec G. Source: Biochemical and Biophysical Research Communications. 2002 May 3; 293(2): 836-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12054546&dopt=Abstract
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Reduction of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down syndrome brain. Author(s): Weitzdoerfer R, Stolzlechner D, Dierssen M, Ferreres J, Fountoulakis M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 347-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771757&dopt=Abstract
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Refractive errors and visual anomalies in Down syndrome. Author(s): Merrick J, Koslowe K. Source: Downs Syndr Res Pract. 2001 July; 6(3): 131-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501216&dopt=Abstract
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Refractive errors in young children with Down syndrome. Author(s): Woodhouse JM, Pakeman VH, Cregg M, Saunders KJ, Parker M, Fraser WI, Sastry P, Lobo S. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 1997 October; 74(10): 844-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383798&dopt=Abstract
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Regional and cellular specificity of the expression of TPRD, the tetratricopeptide Down syndrome gene, during human embryonic development. Author(s): Rachidi M, Lopes C, Gassanova S, Sinet PM, Vekemans M, Attie T, Delezoide AL, Delabar JM. Source: Mechanisms of Development. 2000 May; 93(1-2): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10781955&dopt=Abstract
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Regional cerebral blood flow in Down syndrome adults during the Wisconsin Card Sorting Test: exploring cognitive activation in the context of poor performance. Author(s): Schapiro MB, Berman KF, Alexander GE, Weinberger DR, Rapoport SI. Source: Biological Psychiatry. 1999 May 1; 45(9): 1190-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10331111&dopt=Abstract
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Relation of age and apolipoprotein E to cognitive function in Down syndrome adults. Author(s): Alexander GE, Saunders AM, Szczepanik J, Strassburger TL, Pietrini P, Dani A, Furey ML, Mentis MJ, Roses AD, Rapoport SI, Schapiro MB. Source: Neuroreport. 1997 May 27; 8(8): 1835-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9223061&dopt=Abstract
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Relations of motor and vocal milestones in typically developing infants and infants with Down syndrome. Author(s): Cobo-Lewis AB, Oller DK, Lynch MP, Levine SL. Source: Am J Ment Retard. 1996 March; 100(5): 456-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8852298&dopt=Abstract
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Relationship between genetic anomalies of different levels and deviations in dermatoglyphic traits. Part 4: Dermatoglyphic peculiarities of males and females with Down syndrome. Family study. Author(s): Katznelson MB, Bejerano M, Yakovenko K, Kobyliansky E. Source: Anthropol Anz. 1999 September; 57(3): 193-255. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10584152&dopt=Abstract
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Relationship of chromosome 21 and acute leukemia in children with Down syndrome. Author(s): Taub JW. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 2001 March-April; 23(3): 175-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305722&dopt=Abstract
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Relationships between self-regulation and personality scores of persons with Down syndrome. Author(s): Kojima M, Ikeda Y. Source: Percept Mot Skills. 2001 December; 93(3): 705-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11806590&dopt=Abstract
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Relative involvement of chromosome #21 in radiation induced exchange aberrations in lymphocytes of Down syndrome patients. Author(s): Grigorova M, Natarajan AT. Source: Mutation Research. 1998 August 3; 404(1-2): 67-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9729283&dopt=Abstract
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Relinquishment of infants with Down syndrome in Israel: trends by time. Author(s): Sadetzki S, Chetrit A, Akstein E, Keinan L, Luxenburg O, Modan B. Source: Am J Ment Retard. 2000 November; 105(6): 480-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11958201&dopt=Abstract
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Renal anomalies in Down syndrome. Author(s): Subrahmanyam AB, Mehta AV. Source: Pediatric Nephrology (Berlin, Germany). 1995 April; 9(2): 253-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7794730&dopt=Abstract
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Renal disease in Down syndrome: autopsy study with emphasis on glomerular lesions. Author(s): Lo A, Brown HG, Fivush BA, Neu AM, Racusen LC. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1998 February; 31(2): 329-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9469506&dopt=Abstract
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Renal transplantation in children with Down syndrome. Author(s): Ehrich JH, Wolff G. Source: Pediatric Transplantation. 1998 August; 2(3): 182-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084739&dopt=Abstract
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Renal transplantation in Down syndrome: a report of the North American Pediatric Renal Transplant Cooperative Study. Author(s): Baqi N, Tejani A, Sullivan EK. Source: Pediatric Transplantation. 1998 August; 2(3): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10084745&dopt=Abstract
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Repeat testing in antenatal screening for Down syndrome using dimeric inhibin-A in combination with other maternal serum markers. Author(s): Hackshaw AK, Wald NJ. Source: Prenatal Diagnosis. 2001 January; 21(1): 58-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11180243&dopt=Abstract
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Report and abstracts of the ninth international workshop on the molecular biology of human chromosome 21 and Down syndrome. Bar Harbor, Maine, USA. 23-26 September 2000. Author(s): Pediatr Surg Int. 2001 Sep;17(7):588 Source: Cytogenetics and Cell Genetics. 2001; 92(1-2): 1-22. Erratum In: Cytogenet Cell Genet 2001; 93(1-2): 144. /entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11666071
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Reproducibility in the measurement of atlanto-occipital instability in children with Down syndrome. Author(s): Karol LA, Sheffield EG, Crawford K, Moody MK, Browne RH. Source: Spine. 1996 November 1; 21(21): 2463-7; Discussion 2468. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8923632&dopt=Abstract
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Respiratory arrest after anterior cervical discectomy and arthrodesis in a patient with Down syndrome. A case report and review of the literature. Author(s): McCance SE, Smith MD. Source: The Journal of Bone and Joint Surgery. American Volume. 1999 December; 81(12): 1741-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10608386&dopt=Abstract
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Right heart obstruction from a balloon-like sinus of Valsalva aneurysm in a patient with Down syndrome. Author(s): Lee SD, Joseph M, Lambert AS, Mazer CD, Hutchison SJ. Source: The Canadian Journal of Cardiology. 2002 April; 18(4): 433-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992138&dopt=Abstract
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Risk factors for heart defects in Down syndrome. Author(s): Faivre L, Vekemans M. Source: Teratology. 1999 March; 59(3): 132. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194802&dopt=Abstract
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Risk of abnormal triple screen for Down syndrome is significantly higher in patients with female fetuses. Author(s): Spong CY, Ghidini A, Stanley-Christian H, Meck JM, Seydel FD, Pezzullo JC. Source: Prenatal Diagnosis. 1999 April; 19(4): 337-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327139&dopt=Abstract
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Risk of amniocentesis in women screened positive for Down syndrome with second trimester maternal serum markers. Author(s): Muller F, Thibaud D, Poloce F, Gelineau MC, Bernard M, Brochet C, Millet C, Real JY, Dommergues M. Source: Prenatal Diagnosis. 2002 November; 22(11): 1036-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12424771&dopt=Abstract
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Risk of Down syndrome and any clinically significant chromosome defect in pregnancies with abnormal triple-screen and normal targeted ultrasonographic results. Author(s): Bahado-Singh RO, Tan A, Deren O, Hunter D, Copel J, Mahoney MJ. Source: American Journal of Obstetrics and Gynecology. 1996 October; 175(4 Pt 1): 824-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8885729&dopt=Abstract
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Role of increased cerebral myo-inositol in the dementia of Down syndrome. Author(s): Shonk T, Ross BD. Source: Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. 1995 June; 33(6): 858-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7651126&dopt=Abstract
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Role of iron in Alzheimer-type dementia in Down syndrome. Author(s): Prasher VP, Gosling P, Blair J. Source: International Journal of Geriatric Psychiatry. 1998 November; 13(11): 818-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9850881&dopt=Abstract
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Role of prenatal ultrasonography in women with positive screen for Down syndrome on the basis of maternal serum markers. Author(s): Nyberg DA, Luthy DA, Cheng EY, Sheley RC, Resta RG, Williams MA. Source: American Journal of Obstetrics and Gynecology. 1995 October; 173(4): 1030-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7485289&dopt=Abstract
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Role of ultrasound for Down syndrome screening in advanced maternal age. Author(s): Egan JF, Malakh L, Turner GW, Markenson G, Wax JR, Benn PA. Source: American Journal of Obstetrics and Gynecology. 2001 November; 185(5): 102831. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717626&dopt=Abstract
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Safety of neck rotation for ear surgery in children with Down syndrome. Author(s): Todd NW, Holt PJ, Allen AT. Source: The Laryngoscope. 2000 September; 110(9): 1442-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10983939&dopt=Abstract
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Schwangerschafts protein 1 (SP1) adds little to the age-related detection of fetal Down syndrome in the first trimester of pregnancy. Author(s): Kornman LH, Morssink LP, Ten Hoor KA, De Wolf BT, Kloosterman MD, Beekhuis JR, Mantingh A. Source: Prenatal Diagnosis. 1998 October; 18(10): 1086-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9826903&dopt=Abstract
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Schwangerschaftsprotein 1 (SP1) as a maternal serum marker for Down syndrome in the first and second trimesters. Author(s): Qin QP, Christiansen M, Nguyen TH, Sorensen S, Larsen SO, NorgaardPedersen B. Source: Prenatal Diagnosis. 1997 February; 17(2): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9061756&dopt=Abstract
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Screening and counseling for Down syndrome. Author(s): Nicklin DE. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2000 March-April; 13(2): 160. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10764205&dopt=Abstract
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Screening for Down syndrome at 14 weeks of pregnancy. Author(s): Wald NJ, Watt HC, Haddow JE, Knight GJ. Source: Prenatal Diagnosis. 1998 March; 18(3): 291-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9556047&dopt=Abstract
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Screening for Down syndrome using first-trimester ultrasound and second-trimester maternal serum markers in a low-risk population: a prospective longitudinal study. Author(s): Audibert F, Dommergues M, Benattar C, Taieb J, Thalabard JC, Frydman R. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2001 July; 18(1): 26-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11489221&dopt=Abstract
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Second trimester levels of maternal serum total activin A and placental inhibin/activin alpha and betaA subunit messenger ribonucleic acids in Down syndrome pregnancy. Author(s): Lambert-Messerlian GM, Luisi S, Florio P, Mazza V, Canick JA, Petraglia F. Source: European Journal of Endocrinology / European Federation of Endocrine Societies. 1998 April; 138(4): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9578511&dopt=Abstract
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Second trimester maternal serum screening using alpha fetoprotein, free beta human chorionic gonadotropin and maternal age specific risk: result of chromosomal abnormalities detected in screen positive for Down syndrome in an Asian population. Author(s): Chao AS, Chung CL, Wu CD, Chang SD, Cheng PJ, Lin YT, Soong YK. Source: Acta Obstetricia Et Gynecologica Scandinavica. 1999 May; 78(5): 393-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10326883&dopt=Abstract
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Second-trimester maternal serum CA-125 versus estriol in the multiple-marker screening test for Down syndrome. Author(s): Wenstrom KD, Owen J, Boots L. Source: Obstetrics and Gynecology. 1997 March; 89(3): 359-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9052585&dopt=Abstract
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Second-trimester maternal serum inhibin-A screening for fetal Down syndrome in Asian women. Author(s): Lam YH, Tang MH. Source: Prenatal Diagnosis. 1999 May; 19(5): 463-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10360516&dopt=Abstract
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Second-trimester prenatal screening for Down syndrome and the relationship of maternal serum biochemical markers to pregnancy complications with adverse outcome. Author(s): Spencer K. Source: Prenatal Diagnosis. 2000 August; 20(8): 652-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951476&dopt=Abstract
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Second-trimester ultrasound to detect fetuses with Down syndrome: a meta-analysis. Author(s): Smith-Bindman R, Hosmer W, Feldstein VA, Deeks JJ, Goldberg JD. Source: Jama : the Journal of the American Medical Association. 2001 February 28; 285(8): 1044-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11209176&dopt=Abstract
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Selective upregulation of the ubiquitin-proteasome proteolytic pathway proteins, proteasome zeta chain and isopeptidase T in fetal Down syndrome. Author(s): Engidawork E, Juranville JF, Fountoulakis M, Dierssen M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 117-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771738&dopt=Abstract
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Self-regulatory behaviors in children with Down syndrome and typically developing children measured using the Goodman Lock Box. Author(s): Gilmore L, Cuskelly M, Hayes A. Source: Research in Developmental Disabilities. 2003 March-April; 24(2): 95-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623080&dopt=Abstract
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Sequential first and second trimester screening tests: correlation of the markers' levels in normal versus Down syndrome affected pregnancies. Author(s): Maymon R, Bergman M, Segal S, Dreazen E, Weinraub Z, Herman A. Source: Prenatal Diagnosis. 2001 December; 21(13): 1175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11787048&dopt=Abstract
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Seroprevalence of hepatitis a antibodies in a group of normal and Down syndrome children in Porto Alegre, southern Brazil. Author(s): Ferreira CT, Leite JC, Tanaguchi AN, Vieira SM, Pereira-Lima J, da Silveira TR. Source: The Brazilian Journal of Infectious Diseases : an Official Publication of the Brazilian Society of Infectious Diseases. 2002 October; 6(5): 225-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495604&dopt=Abstract
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Serotonin (5-HT) in brains of adult patients with Down syndrome. Author(s): Seidl R, Kaehler ST, Prast H, Singewald N, Cairns N, Gratzer M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 221-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666678&dopt=Abstract
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Serum hyperglycosylated hCG: a potential screening test for fetal Down syndrome. Author(s): Shahabi S, Oz UA, Bahado-Singh RO, Mahoney MJ, Omrani A, Baumgarten A, Cole LA. Source: Prenatal Diagnosis. 1999 May; 19(5): 488-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10360522&dopt=Abstract
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Serum leptin concentrations in obese women with Down syndrome and Prader-Willi syndrome. Author(s): Cento RM, Proto C, Spada RS, Ragusa L, Reitano S, Napolitano V, Lanzone A. Source: Gynecological Endocrinology : the Official Journal of the International Society of Gynecological Endocrinology. 1999 February; 13(1): 36-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10368796&dopt=Abstract
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Serum NGF levels in children and adolescents with either Williams syndrome or Down syndrome. Author(s): Calamandrei G, Alleva E, Cirulli F, Queyras A, Volterra V, Capirci O, Vicari S, Giannotti A, Turrini P, Aloe L. Source: Developmental Medicine and Child Neurology. 2000 November; 42(11): 746-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11104346&dopt=Abstract
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Serum screening for Down syndrome and adverse pregnancy outcomes: a casecontrolled study. Author(s): Ogle R, Jauniaux E, Pahal GS, Dell E, Sheldrake A, Rodeck C. Source: Prenatal Diagnosis. 2000 February; 20(2): 96-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10694681&dopt=Abstract
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Severe impairment of secretory Ig production in parotid saliva of Down syndrome individuals. Author(s): Dawes C. Source: Journal of Dental Research. 2002 September; 81(9): 588; Author Reply 588-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12202636&dopt=Abstract
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Sharing laughter: the humour of pre-school children with Down syndrome. Author(s): Reddy V, Williams E, Vaughan A. Source: Downs Syndr Res Pract. 2001 October; 7(3): 125-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721537&dopt=Abstract
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Short-term memory in Down syndrome: applying the working memory model. Author(s): Jarrold C, Baddeley AD. Source: Downs Syndr Res Pract. 2001 October; 7(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706808&dopt=Abstract
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Should children with Down syndrome be screened for atlantoaxial instability? Author(s): Pueschel SM. Source: Archives of Pediatrics & Adolescent Medicine. 1998 February; 152(2): 123-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9491036&dopt=Abstract
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Should sonographic screening for fetal Down syndrome be applied to low risk women? Author(s): Benacerraf BR. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2000 June; 15(6): 451-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11005109&dopt=Abstract
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Significance of autoantibodies to oxidatively modified LDL in plasma of children with Down syndrome. Author(s): Fulgenzi A, Wasserman K, Corsi MM. Source: Clinical Chemistry. 2001 June; 47(6): 1135-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375314&dopt=Abstract
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Significance of oral health in persons with Down syndrome: a literature review. Author(s): Hennequin M, Faulks D, Veyrune JL, Bourdiol P. Source: Developmental Medicine and Child Neurology. 1999 April; 41(4): 275-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10355815&dopt=Abstract
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Signing and lexical development in children with Down syndrome. Author(s): Clibbens J. Source: Downs Syndr Res Pract. 2001 October; 7(3): 101-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721535&dopt=Abstract
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Similar deficits of central histaminergic system in patients with Down syndrome and Alzheimer disease. Author(s): Schneider C, Risser D, Kirchner L, Kitzmuller E, Cairns N, Prast H, Singewald N, Lubec G. Source: Neuroscience Letters. 1997 February 7; 222(3): 183-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9148245&dopt=Abstract
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Size of ventricular structures influences surgical outcome in Down syndrome infants with atrioventricular septal defect. Author(s): Minich LL, Tani LY, Pagotto LT, Hawkins JA, McGough EC, Shaddy RE. Source: The American Journal of Cardiology. 1998 April 15; 81(8): 1062-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9576172&dopt=Abstract
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Sleep characteristics in children with Down syndrome. Author(s): Levanon A, Tarasiuk A, Tal A. Source: The Journal of Pediatrics. 1999 June; 134(6): 755-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10356146&dopt=Abstract
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Software for prenatal down syndrome risk calculation: a comparative study of six software packages. Author(s): Muller F, Aegerter P, Ngo S, Fort A, Beauchet A, Giraudet P, Dommergues M. Source: Clinical Chemistry. 1999 August; 45(8 Pt 1): 1278-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10430795&dopt=Abstract
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Sonographic identification of fetuses with Down syndrome in the third trimester: a matched control study. Author(s): Ranzini AC, Guzman ER, Ananth CV, Day-Salvatore D, Fisher AJ, Vintzileos AM. Source: Obstetrics and Gynecology. 1999 May; 93(5 Pt 1): 702-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912971&dopt=Abstract
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Sonographic nuchal markers for Down syndrome are more common but less ominous in gestations with a male fetus. Author(s): Drugan A, Weissman A, Avrahami R, Zamir R, Evans MI. Source: Fetal Diagnosis and Therapy. 2002 September-October; 17(5): 295-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169815&dopt=Abstract
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SP1 in pregnancies with Down syndrome in the first trimester of pregnancy. International Prenatal Screening Research Group. Author(s): Wald NJ, Watt HC, Norgaard-Pedersen B, Christiansen M. Source: Prenatal Diagnosis. 1999 June; 19(6): 517-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10416965&dopt=Abstract
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Spatial representation and attention in toddlers with Williams syndrome and Down syndrome. Author(s): Brown JH, Johnson MH, Paterson SJ, Gilmore R, Longhi E, Karmiloff-Smith A. Source: Neuropsychologia. 2003; 41(8): 1037-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12667539&dopt=Abstract
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Spectrum of congenital heart defects associated with Down Syndrome in high consanguineous Omani population. Author(s): Venugopalan P, Agarwal AK. Source: Indian Pediatrics. 2003 May; 40(5): 398-403. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12768040&dopt=Abstract
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Speech production errors in adults with and without Down syndrome following verbal, written, and pictorial cues. Author(s): Bunn L, Simon DA, Welsh TN, Watson C, Elliott D. Source: Developmental Neuropsychology. 2002; 21(2): 157-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139197&dopt=Abstract
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Spinal arthrodesis for scoliosis in Down syndrome. Author(s): Lerman JA, Emans JB, Hall JE, Karlin LI. Source: Journal of Pediatric Orthopedics. 2003 March-April; 23(2): 159-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12604943&dopt=Abstract
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Sports participation of children with Down syndrome. Author(s): Winell J, Burke SW. Source: The Orthopedic Clinics of North America. 2003 July; 34(3): 439-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12974493&dopt=Abstract
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Stamps in cardiology: Down syndrome. Author(s): Davies MK, Hollman A. Source: Heart (British Cardiac Society). 2001 August; 86(2): 130. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454822&dopt=Abstract
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Stimulated parotid salivary flow rate in patients with Down syndrome. Author(s): Chaushu S, Becker A, Chaushu G, Shapira J. Source: Spec Care Dentist. 2002 January-February; 22(1): 41-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12014860&dopt=Abstract
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Stimulated whole saliva components in children with Down syndrome. Author(s): Siqueira WL, Nicolau J. Source: Spec Care Dentist. 2002 November-December; 22(6): 226-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12790231&dopt=Abstract
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Structure and coherence of reasoning ability in Down Syndrome adults and typically developing children. Author(s): Natsopoulo D, Christou C, Koutselini M, Raftopoulos A, Karefillidou C. Source: Research in Developmental Disabilities. 2002 July-August; 23(4): 297-307. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365854&dopt=Abstract
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Structure and polymorphism of the human gene for the interferon-induced p78 protein (MX1): evidence of association with alopecia areata in the Down syndrome region. Author(s): Tazi-Ahnini R, di Giovine FS, McDonagh AJ, Messenger AG, Amadou C, Cox A, Duff GW, Cork MJ. Source: Human Genetics. 2000 June; 106(6): 639-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10942113&dopt=Abstract
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Study of Down syndrome in 238,942 consecutive births. Author(s): Stoll C, Alembik Y, Dott B, Roth MP. Source: Annales De Genetique. 1998; 41(1): 44-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9599651&dopt=Abstract
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Subtle ultrasonographic anomalies: do they improve the Down syndrome detection rate? Author(s): Deren O, Mahoney MJ, Copel JA, Bahado-Singh RO. Source: American Journal of Obstetrics and Gynecology. 1998 March; 178(3): 441-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9539505&dopt=Abstract
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Successful pregnancy and delivery from frozen-thawed embryos after intracytoplasmic sperm injection using round-headed spermatozoa and assisted oocyte activation in a globozoospermic patient with mosaic Down syndrome. Author(s): Kim ST, Cha YB, Park JM, Gye MC. Source: Fertility and Sterility. 2001 February; 75(2): 445-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11172857&dopt=Abstract
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Superior sagittal sinus thrombosis in a child with Down syndrome. Author(s): Williams M, Nand S. Source: Journal of Paediatrics and Child Health. 2003 April; 39(3): 226-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12654149&dopt=Abstract
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Superoxide dismutase SOD1, encoded on chromosome 21, but not SOD2 is overexpressed in brains of patients with Down syndrome. Author(s): Gulesserian T, Seidl R, Hardmeier R, Cairns N, Lubec G. Source: Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research. 2001 January; 49(1): 41-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217146&dopt=Abstract
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Survey of attitudes of pregnant women towards Down syndrome screening. Author(s): Al-Jader LN, Parry-Langdon N, Smith RJ. Source: Prenatal Diagnosis. 2000 January; 20(1): 23-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701846&dopt=Abstract
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Survival of children with Down syndrome in South America. ECLAMC-Downsurv Group. Latin American Collaborative Study of Congenital Malformations. Author(s): Castilla EE, Rittler M, Dutra MG, Lopez-Camelo JS, Campana H, Paz JE, Orioli IM. Source: American Journal of Medical Genetics. 1998 September 1; 79(2): 108-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9741468&dopt=Abstract
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Survival of Down syndrome in utero. Author(s): Benn PA, Egan JF. Source: Prenatal Diagnosis. 2000 May; 20(5): 432-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10820415&dopt=Abstract
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Susceptibility to leukemia and resistance to solid tumors in Down syndrome. Author(s): Zipursky A. Source: Pediatric Research. 2000 June; 47(6): 704. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10832723&dopt=Abstract
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Synaptosomal proteins, beta-soluble N-ethylmaleimide-sensitive factor attachment protein (beta-SNAP), gamma-SNAP and synaptotagmin I in brain of patients with Down syndrome and Alzheimer's disease. Author(s): Yoo BC, Cairns N, Fountoulakis M, Lubec G. Source: Dementia and Geriatric Cognitive Disorders. 2001 May-June; 12(3): 219-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11244216&dopt=Abstract
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Systemic lupus erythematosus associated with Down syndrome. Author(s): Suwa A, Hirakata M, Satoh S, Ezaki T, Mimori T, Inada S. Source: Clin Exp Rheumatol. 2000 September-October; 18(5): 650-1. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11072615&dopt=Abstract
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Task-related social behavior in children with Down syndrome. Author(s): Kasari C, Freeman SF. Source: Am J Ment Retard. 2001 May; 106(3): 253-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11389666&dopt=Abstract
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Teaching basic skills to children with Down syndrome and developmental delays: the relative efficacy of interactive modeling with social rewards for benchmark achievements and passive observation. Author(s): Biederman GB, Fairhall JL, Raven KA, Davey VA. Source: Downs Syndr Res Pract. 1998; 5(1): 26-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890857&dopt=Abstract
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Teenagers with Down syndrome study algebra in High School. Author(s): Martinez EM. Source: Downs Syndr Res Pract. 1998; 5(1): 34-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890858&dopt=Abstract
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Temperament in children with Down syndrome and in prematurely born children. Author(s): Nygaard E, Smith L, Torgersen AM. Source: Scandinavian Journal of Psychology. 2002 February; 43(1): 61-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11885761&dopt=Abstract
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Testicular germ cell tumor and Down syndrome. Author(s): Villanueva MJ, Navarro F, Sanchez A, Provencio M, Bonilla F, Espana P. Source: Tumori. 2000 September-October; 86(5): 431-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11130577&dopt=Abstract
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The “gene dosage effect” hypothesis versus the “amplified developmental instability” hypothesis in Down syndrome. Author(s): Pritchard MA, Kola I. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 293-303. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666684&dopt=Abstract
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The 129 codon polymorphism of the prion protein gene influences earlier cognitive performance in Down syndrome subjects. Author(s): Del Bo R, Comi GP, Giorda R, Crimi M, Locatelli F, Martinelli-Boneschi F, Pozzoli U, Castelli E, Bresolin N, Scarlato G. Source: Journal of Neurology. 2003 June; 250(6): 688-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796830&dopt=Abstract
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The anterior iliac separation: alternative index for pelvic morphometry in fetuses with Down syndrome. Author(s): Kliewer MA, Hertzberg BS, Freed KS, McNally PJ, DeLong DM. Source: Ajr. American Journal of Roentgenology. 2001 April; 176(4): 1003-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11264098&dopt=Abstract
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The association between congenital heart disease and Down syndrome in prenatal life. Author(s): Paladini D, Tartaglione A, Agangi A, Teodoro A, Forleo F, Borghese A, Martinelli P. Source: Ultrasound in Obstetrics & Gynecology : the Official Journal of the International Society of Ultrasound in Obstetrics and Gynecology. 2000 February; 15(2): 104-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10775990&dopt=Abstract
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The Caenorhabditis elegans homologue of Down syndrome critical region 1, RCN-1, inhibits multiple functions of the phosphatase calcineurin. Author(s): Lee JI, Dhakal BK, Lee J, Bandyopadhyay J, Jeong SY, Eom SH, Kim do H, Ahnn J. Source: Journal of Molecular Biology. 2003 April 18; 328(1): 147-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12684004&dopt=Abstract
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The comprehensive midtrimester test: high-sensitivity Down syndrome test. Author(s): Bahado-Singh R, Shahabi S, Karaca M, Mahoney MJ, Cole L, Oz UA. Source: American Journal of Obstetrics and Gynecology. 2002 April; 186(4): 803-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11967511&dopt=Abstract
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The differentially expressed C21orf5 gene in the medial temporal-lobe system could play a role in mental retardation in Down syndrome and transgenic mice. Author(s): Lopes C, Chettouh Z, Delabar JM, Rachidi M. Source: Biochemical and Biophysical Research Communications. 2003 June 13; 305(4): 915-24. Erratum In: Biochem Biophys Res Commun. 2003 August 1; 307(3): 758. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767918&dopt=Abstract
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The Down syndrome critical region. Author(s): Shapiro BL. Source: Journal of Neural Transmission. Supplementum. 1999; 57: 41-60. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10666667&dopt=Abstract
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The effect of age, size of target, and cognitive factors on accommodative responses of children with Down syndrome. Author(s): Woodhouse JM, Cregg M, Gunter HL, Sanders DP, Saunders KJ, Pakeman VH, Parker M, Fraser WI, Sastry P. Source: Investigative Ophthalmology & Visual Science. 2000 August; 41(9): 2479-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10937557&dopt=Abstract
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The effect of fast reporting by amnio-PCR on anxiety levels in women with positive biochemical screening for Down syndrome--a randomized controlled trial. Author(s): Leung WC, Lam YH, Wong Y, Lau ET, Tang MH. Source: Prenatal Diagnosis. 2002 March; 22(3): 256-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11920905&dopt=Abstract
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The effect of foot orthoses on standing foot posture and gait of young children with Down syndrome. Author(s): Selby-Silverstein L, Hillstrom HJ, Palisano RJ. Source: Neurorehabilitation. 2001; 16(3): 183-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11790903&dopt=Abstract
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The effects of early motor intervention on children with Down syndrome or cerebral palsy: a field-based study. Author(s): Mahoney G, Robinson C, Fewell RR. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 2001 June; 22(3): 15362. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11437190&dopt=Abstract
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The effects of quality of life models on the development of research and practice in the field of Down syndrome. Author(s): Brown RI. Source: Downs Syndr Res Pract. 1998; 5(1): 39-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890859&dopt=Abstract
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The genetic sonogram in screening for Down syndrome. Author(s): Smith-Bindman R, Feldstein VA, Goldberg JD. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2001 November; 20(11): 1153-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11758019&dopt=Abstract
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The genetic sonogram in screening for Down syndrome: response to the JAMA study. Author(s): Hobbins JC, Bahado-Singh RO, Lezotte DC. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2001 June; 20(6): 269-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400929&dopt=Abstract
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The genetic sonogram: a method of risk assessment for Down syndrome in the second trimester. Author(s): Bromley B, Lieberman E, Shipp TD, Benacerraf BR. Source: Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine. 2002 October; 21(10): 1087-96; Quiz 1097-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12369663&dopt=Abstract
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The impact of risk factors of Alzheimer's disease in the Down syndrome. Author(s): Folin M, Baiguera S, Conconi MT, Pati T, Grandi C, Parnigotto PP, Nussdorfer GG. Source: International Journal of Molecular Medicine. 2003 February; 11(2): 267-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12525890&dopt=Abstract
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The impact of the use of the isolated echogenic intracardiac focus as a screen for Down syndrome in women under the age of 35 years. Author(s): Caughey AB, Lyell DJ, Filly RA, Washington AE, Norton ME. Source: American Journal of Obstetrics and Gynecology. 2001 November; 185(5): 1021-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11717625&dopt=Abstract
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The implications of a false positive second-trimester serum screen for Down syndrome. Author(s): Summers AM, Huang T, Meier C, Wyatt PR. Source: Obstetrics and Gynecology. 2003 June; 101(6): 1301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798540&dopt=Abstract
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The influence of fetal sex in screening for Down syndrome in the second trimester using AFP and free beta-hCG. Author(s): Spencer K. Source: Prenatal Diagnosis. 2000 August; 20(8): 648-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10951475&dopt=Abstract
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The influence of paternal age on down syndrome. Author(s): Fisch H, Hyun G, Golden R, Hensle TW, Olsson CA, Liberson GL. Source: The Journal of Urology. 2003 June; 169(6): 2275-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12771769&dopt=Abstract
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The joy of having a child with Down syndrome. Author(s): Latini G. Source: Acta Paediatrica (Oslo, Norway : 1992). 2002; 91(12): 1291-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12578282&dopt=Abstract
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The linguistic and cognitive profile of Down syndrome: evidence from a comparison with fragile X syndrome. Author(s): Abbeduto L, Pavetto M, Kesin E, Weissman MD, Karadottir S, O'Brien A, Cawthon S. Source: Downs Syndr Res Pract. 2001 October; 7(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706811&dopt=Abstract
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The National Down Syndrome Cytogenetic Register (NDSCR). Author(s): Alberman E. Source: Journal of Medical Screening. 2002; 9(3): 97-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12370318&dopt=Abstract
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The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Author(s): Pennington BF, Moon J, Edgin J, Stedron J, Nadel L. Source: Child Development. 2003 January-February; 74(1): 75-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12625437&dopt=Abstract
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The oral assessment in Down syndrome questionnaire (OADS): development of an instrument to evaluate oral health problems in individuals with Down syndrome. Author(s): Allison PJ, Hennequin M. Source: Community Dent Health. 2000 September; 17(3): 172-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11108405&dopt=Abstract
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The preparation of reach to grasp movements in adults with Down syndrome. Author(s): Mon-Williams M, Tresilian JR, Bell VE, Coppard VL, Jobling A, Carson RG. Source: Human Movement Science. 2001 November; 20(4-5): 587-602. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11750679&dopt=Abstract
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The reduction of NADH ubiquinone oxidoreductase 24- and 75-kDa subunits in brains of patients with Down syndrome and Alzheimer's disease. Author(s): Kim SH, Vlkolinsky R, Cairns N, Fountoulakis M, Lubec G. Source: Life Sciences. 2001 May 4; 68(24): 2741-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11400916&dopt=Abstract
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The relation between the psychological functioning of children with Down syndrome and their urine peptide levels and levels of serum antibodies to food proteins. Author(s): Nygaard E, Reichelt KL, Fagan JF. Source: Downs Syndr Res Pract. 2001 July; 6(3): 139-45. Erratum In: Downs Syndr Res Pract 2002 March; 8(1): 37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501218&dopt=Abstract
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The relationship between event representation and linguistic skill in narratives of children and adolescents with Down syndrome. Author(s): Boudreau DM, Chapman RS. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 2000 October; 43(5): 1146-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063236&dopt=Abstract
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The relevance of a nonword repetition task to assess phonological short-term memory in individuals with Down syndrome. Author(s): Comblain A. Source: Downs Syndr Res Pract. 1999 September; 6(2): 76-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11276982&dopt=Abstract
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The role of p53 in megakaryocyte differentiation and the megakaryocytic leukemias of Down syndrome. Author(s): Malkin D, Brown EJ, Zipursky A. Source: Cancer Genetics and Cytogenetics. 2000 January 1; 116(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10616523&dopt=Abstract
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The sequence of human chromosome 21 and implications for research into Down syndrome. Author(s): Gardiner K, Davisson M. Source: Genome Biology. 2000; 1(2): Reviews0002. Epub 2000 August 04. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11178230&dopt=Abstract
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The utilisation of nuchal translucency as a prenatal marker of Down syndrome, 19931999. Author(s): Mulvey SF, Atchison WG, Grimwade JC, Renou PM, Shekleton PA, Wallace EM. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2000 November; 40(4): 423-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11194428&dopt=Abstract
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The variation of risk estimates through pregnancy in second trimester maternal serum screening for Down syndrome. Author(s): Christiansen M, Hogdall EV, Larsen SO, Hogdall C. Source: Prenatal Diagnosis. 2002 May; 22(5): 385-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001192&dopt=Abstract
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The World Association movement for Down syndrome. Author(s): Perera J. Source: Downs Syndr Res Pract. 1999 August; 6(1): 43-7. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890246&dopt=Abstract
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Third molar agenesis in Down syndrome. Author(s): Lomholt JF, Russell BG, Stoltze K, Kjaer I. Source: Acta Odontologica Scandinavica. 2002 June; 60(3): 151-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12166908&dopt=Abstract
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Too much of a good thing: mechanisms of gene action in Down syndrome. Author(s): Reeves RH, Baxter LL, Richtsmeier JT. Source: Trends in Genetics : Tig. 2001 February; 17(2): 83-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11173117&dopt=Abstract
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Tooth wear in children with Down syndrome. Author(s): Bell EJ, Kaidonis J, Townsend GC. Source: Aust Dent J. 2002 March; 47(1): 30-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12035955&dopt=Abstract
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Towards optimal mental health of persons with Down syndrome. Author(s): Pueschel SM. Source: Downs Syndr Res Pract. 1998; 5(1): 43-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890860&dopt=Abstract
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Tracheal stenosis and congenital heart disease in patients with Down syndrome: diagnostic approach and surgical options. Author(s): Shapiro NL, Huang RY, Sangwan S, Willner A, Laks H. Source: International Journal of Pediatric Otorhinolaryngology. 2000 August 31; 54(2-3): 137-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10967384&dopt=Abstract
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Training phonological awareness skills in children with Down syndrome. Author(s): Kennedy EJ, Flynn MC. Source: Research in Developmental Disabilities. 2003 January-February; 24(1): 44-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12553967&dopt=Abstract
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Transient myeloproliferative disorder and acute myeloid leukemia in Down syndrome. An immunophenotypic analysis. Author(s): Karandikar NJ, Aquino DB, McKenna RW, Kroft SH. Source: American Journal of Clinical Pathology. 2001 August; 116(2): 204-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488066&dopt=Abstract
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Transient myeloproliferative disorder in Down syndrome presenting with ascites: a case report. Author(s): Shiffer J, Natarajan S. Source: Acta Cytol. 2001 July-August; 45(4): 610-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11480727&dopt=Abstract
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Transient myeloproliferative disorder with erythroid differentiation in Down syndrome. Author(s): Bozner P. Source: Archives of Pathology & Laboratory Medicine. 2002 April; 126(4): 474-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11900577&dopt=Abstract
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Transient myeloproliferative syndrome/transient acute myeloid leukemia in a newborn with Down syndrome: a case report and literature review. Author(s): D'Angelo G, Merlo P. Source: Lab Hematol. 2003; 9(1): 38-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661826&dopt=Abstract
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Translocation Down syndrome. Author(s): Jyothy A, Rao GN, Kumar KS, Rao VB, Uma Devi B, Reddy PP. Source: Indian Journal of Medical Sciences. 2002 May; 56(5): 225-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649945&dopt=Abstract
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Translocation Down syndrome. Author(s): Jyothy A, Rao GN, Kumar KS, Rao VB, Devi BU, Reddy PP. Source: Indian Journal of Medical Sciences. 2002 March; 56(3): 122-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508621&dopt=Abstract
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Treadmill training of infants with Down syndrome: evidence-based developmental outcomes. Author(s): Ulrich DA, Ulrich BD, Angulo-Kinzler RM, Yun J. Source: Pediatrics. 2001 November; 108(5): E84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11694668&dopt=Abstract
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Treating the patient with Down syndrome. Author(s): Pilcher ES. Source: The Journal of Contemporary Dental Practice [electronic Resource]. 2001 November 15; 2(4): 58. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167922&dopt=Abstract
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Treatment of Down syndrome-associated craniovertebral junction abnormalities. Author(s): Taggard DA, Menezes AH, Ryken TC. Source: Journal of Neurosurgery. 2000 October; 93(2 Suppl): 205-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11012050&dopt=Abstract
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Trends in live birth prevalence of down syndrome in the Northern Netherlands 198796: the impact of screening and prenatal diagnosis. Author(s): Wortelboer MJ, De Wolf BT, Verschuuren-Bemelmans CC, Reefhuis J, Mantingh A, Beekhuis JR, Cornel MC. Source: Prenatal Diagnosis. 2000 September; 20(9): 709-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11015698&dopt=Abstract
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Trisomy 11 limited to trisomy 21 cells in a mosaic Down syndrome child with acute myeloid leukemia. Author(s): Punnett HH, Dampier C. Source: Medical and Pediatric Oncology. 2003 July; 41(1): 69-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764749&dopt=Abstract
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Ts65Dn -- localization of the translocation breakpoint and trisomic gene content in a mouse model for Down syndrome. Author(s): Akeson EC, Lambert JP, Narayanswami S, Gardiner K, Bechtel LJ, Davisson MT. Source: Cytogenetics and Cell Genetics. 2001; 93(3-4): 270-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11528125&dopt=Abstract
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Twin Down syndrome babies: the outcome of a pregnancy following endometrial resection. Author(s): Abdel-Fattah MS, White D, Barrington JW. Source: Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology. 2003 July; 23(4): 436-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12881093&dopt=Abstract
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Ultrasonographic femur-tibial length ratio: a marker of Down syndrome from the late second trimester. Author(s): Gupta R, Thomas RD, Sreenivas V, Walter S, Puliyel JM. Source: American Journal of Perinatology. 2001 June; 18(4): 217-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11444366&dopt=Abstract
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Ultrasound dating in first-trimester biochemical screening for Down syndrome. Author(s): Borrell A, Farre MT, Costa D, Fortuny A. Source: Prenatal Diagnosis. 1996 July; 16(7): 675-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8843482&dopt=Abstract
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Ultrasound markers of fetal Down syndrome. Author(s): Bahado-Singh RO, Mendilcioglu I, Copel J. Source: Jama : the Journal of the American Medical Association. 2001 June 13; 285(22): 2857-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401604&dopt=Abstract
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Ultrasound markers of fetal Down syndrome. Author(s): Egan JF, Rodis JF, Benn PA. Source: Jama : the Journal of the American Medical Association. 2001 June 13; 285(22): 2856-7; Author Reply 2858. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401603&dopt=Abstract
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Ultrasound markers of fetal Down syndrome. Author(s): Nyberg DA. Source: Jama : the Journal of the American Medical Association. 2001 June 13; 285(22): 2856; Author Reply 2858. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11401602&dopt=Abstract
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Ultrastructural studies of the megakaryoblastic leukemias of Down syndrome. Author(s): Zipursky A, Christensen H, De Harven E. Source: Leukemia & Lymphoma. 1995 July; 18(3-4): 341-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8535203&dopt=Abstract
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Unaltered expression of Fas (CD95/APO-1), caspase-3, Bcl-2 and annexins in brains of fetal Down syndrome: evidence against increased apoptosis. Author(s): Engidawork E, Balic N, Juranville JF, Fountoulakis M, Dierssen M, Lubec G. Source: Journal of Neural Transmission. Supplementum. 2001; (61): 149-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771740&dopt=Abstract
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Unconjugated estriol as maternal serum marker for the detection of Down syndrome pregnancies. Author(s): David M, Merksamer R, Israel N, Dar H. Source: Fetal Diagnosis and Therapy. 1996 March-April; 11(2): 99-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8838765&dopt=Abstract
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Understanding metaphors and idioms: a single-case neuropsychological study in a person with Down syndrome. Author(s): Papagno C, Vallar G. Source: Journal of the International Neuropsychological Society : Jins. 2001 May; 7(4): 516-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11396554&dopt=Abstract
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Understanding of learning and cognitive development in Down syndrome. Author(s): Buckley S. Source: Downs Syndr Res Pract. 2001 October; 7(2): V-Vii. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11721534&dopt=Abstract
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Unrelated donor bone marrow transplantation for acute mixed lineage (myeloid and B-lymphoid lineage) leukemia in an adult with Down syndrome. Author(s): Takagi K, Yoshida A, Kinoshita K, Iwashima D, Imamaura S, Iwasaki H, Tsutani H, Ueda T. Source: Annals of Hematology. 2003 April; 82(4): 236-40. Epub 2003 March 14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12707727&dopt=Abstract
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Unusual association of hypertrophic cardiomyopathy with complete atrioventricular canal defect and Down syndrome. Author(s): Eidem BW, Jones C, Cetta F. Source: Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2000; 27(3): 289-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11093415&dopt=Abstract
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Unusual clonal chromosomal evolution in a breast carcinoma and its lymph node metastasis in a patient with Down syndrome. Author(s): Bernardino J, Gerbault-Seureau M, Sastre X, Dutrillaux B. Source: Genes, Chromosomes & Cancer. 1997 July; 19(3): 195-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9219002&dopt=Abstract
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Upper airway obstruction in children with Down syndrome. Author(s): Jacobs IN, Gray RF, Todd NW. Source: Archives of Otolaryngology--Head & Neck Surgery. 1996 September; 122(9): 945-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8797558&dopt=Abstract
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Uptake of Down syndrome screening in an Australian Vietnamese population. Author(s): Nagle C, McCarthy P, Wallace EM. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2000 May; 40(2): 157-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10925901&dopt=Abstract
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Urinary analyte screening: a noninvasive detection method for Down syndrome? Author(s): Canick JA, Kellner LH, Cole LA, Cuckle HS. Source: Molecular Medicine Today. 1999 February; 5(2): 68-73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200947&dopt=Abstract
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Urinary free beta hCG, beta core fragment and total oestriol as markers of Down syndrome in the second trimester of pregnancy. Author(s): Hsu JJ, Spencer K, Aitken DA, Crossley J, Choi T, Ozaki M, Tazawa H. Source: Prenatal Diagnosis. 1999 February; 19(2): 146-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10215073&dopt=Abstract
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Urinary screening tests for fetal Down syndrome: I. Fresh beta-core fragment. Author(s): Cole LA, Rinne KM, Mahajan SM, Oz UA, Shahabi S, Mahoney MJ, BahadoSingh RO. Source: Prenatal Diagnosis. 1999 April; 19(4): 340-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327140&dopt=Abstract
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Urinary screening tests for fetal Down syndrome: II. Hyperglycosylated hCG. Author(s): Cole LA, Shahabi S, Oz UA, Rinne KM, Omrani A, Bahado-Singh RO, Mahoney MJ. Source: Prenatal Diagnosis. 1999 April; 19(4): 351-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327141&dopt=Abstract
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Urinary sulfur compounds in Down syndrome. Author(s): Belardinelli MC, Chabli A, Chadefaux-Vekemans B, Kamoun P. Source: Clinical Chemistry. 2001 August; 47(8): 1500-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11468253&dopt=Abstract
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Urine free beta-hCG and total estriol for Down syndrome screening during the second trimester in an Asian population. Author(s): Hsu JJ, Hsu TY, Hsieh TT, Soong YK, Hsieh FJ, Spencer K. Source: Obstetrics and Gynecology. 1999 July; 94(1): 107-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389728&dopt=Abstract
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Urine hyperglycosylated hCG plus ultrasound biometry for detection of down syndrome in the second trimester in a high-risk population. Author(s): Bahado-Singh R, Oz U, Shahabi S, Omrani A, Mahoney M, Cole L. Source: Obstetrics and Gynecology. 2000 June; 95(6 Pt 1): 889-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10831986&dopt=Abstract
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Use of dental implants in patients with Down syndrome: a case report. Author(s): Lustig JP, Yanko R, Zilberman U. Source: Spec Care Dentist. 2002 September-October; 22(5): 201-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12580359&dopt=Abstract
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Use of pointing and other gestures by young children with Down syndrome. Author(s): Franco F, Wishart JG. Source: Am J Ment Retard. 1995 September; 100(2): 160-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8527112&dopt=Abstract
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Use of sonographic markers to determine the risk of Down syndrome in secondtrimester fetuses. Author(s): Benacerraf BR. Source: Radiology. 1996 December; 201(3): 619-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8939206&dopt=Abstract
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Use of the community-oriented primary care model for a special-needs population: a clinic for adults with Down syndrome. Author(s): Chicoine B, McGuire D, Hebein S, Gilly D. Source: American Journal of Public Health. 1995 June; 85(6): 869-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7762729&dopt=Abstract
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Use of videotapes for viewing at home to inform choice in Down syndrome screening: a randomised controlled trial. Author(s): Hewison J, Cuckle H, Baillie C, Sehmi I, Lindow S, Jackson F, Batty J. Source: Prenatal Diagnosis. 2001 February; 21(2): 146-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241545&dopt=Abstract
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Using active medical record review and capture-recapture methods to investigate the prevalence of Down Syndrome among live-born infants in Colorado. Author(s): Orton H, Rickard R, Miller L. Source: Teratology. 2001; 64 Suppl 1: S14-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11745839&dopt=Abstract
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Using augmentative communication with infants and young children with Down syndrome. Author(s): Foreman P, Crews G. Source: Downs Syndr Res Pract. 1998; 5(1): 16-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10890856&dopt=Abstract
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Using Down syndrome serum screening results to predict low birthweight. Author(s): Huang T, Alberman E, Watt HC, Wald NJ. Source: Prenatal Diagnosis. 2003 May; 23(5): 420-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749041&dopt=Abstract
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Using the gross motor function measure to evaluate motor development in children with Down syndrome. Author(s): Gemus M, Palisano R, Russell D, Rosenbaum P, Walter SD, Galuppi B, Lane M. Source: Phys Occup Ther Pediatr. 2001; 21(2-3): 69-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12029855&dopt=Abstract
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Validation of radiographic criteria for the diagnosis of Down syndrome in stillborn infants. Author(s): Dasgupta NR, Pauli RM, Horton VK, Reiser CA. Source: American Journal of Medical Genetics. 1997 October 31; 72(3): 347-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9332668&dopt=Abstract
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Validation of risk estimation using the quadruple test in prenatal screening for Down syndrome. Author(s): Wald NJ, Huttly WJ. Source: Prenatal Diagnosis. 1999 November; 19(11): 1083-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589068&dopt=Abstract
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Validity of parent report measures of vocabulary development for children with Down syndrome. Author(s): Miller JF, Sedey AL, Miolo G. Source: Journal of Speech and Hearing Research. 1995 October; 38(5): 1037-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8558873&dopt=Abstract
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Value of humerus length shortening for prenatal detection of Down syndrome in a Thai population. Author(s): Tannirandorn Y, Manotaya S, Uerpairojkit B, Tanawattanacharoen S, Wacharaprechanont T, Charoenvidhya D. Source: The Journal of Obstetrics and Gynaecology Research. 2002 April; 28(2): 89-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078975&dopt=Abstract
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Variations in measurement of the iliac angle of the fetal pelvis in Down syndrome. Author(s): Gelman R, Martz BL, Pervola L. Source: Radiology. 1998 March; 206(3): 846-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9494514&dopt=Abstract
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Vascular fibrosis and calcification in the hippocampus in aging, Alzheimer disease, and Down syndrome. Author(s): Wegiel J, Kuchna I, Wisniewski T, de Leon MJ, Reisberg B, Pirttila T, Kivimaki T, Lehtimaki T. Source: Acta Neuropathologica. 2002 April; 103(4): 333-43. Epub 2001 November 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11904752&dopt=Abstract
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Verb use by individuals with Down syndrome. Author(s): Hesketh LJ, Chapman RS. Source: Am J Ment Retard. 1998 November; 103(3): 288-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9833659&dopt=Abstract
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Verbal short-term memory deficits in Down syndrome: a consequence of problems in rehearsal? Author(s): Jarrold C, Baddeley AD, Hewes AK. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2000 February; 41(2): 233-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10750549&dopt=Abstract
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Verbal short-term memory in Down syndrome: a problem of memory, audition, or speech? Author(s): Jarrold C, Baddeley AD, Phillips CE. Source: Journal of Speech, Language, and Hearing Research : Jslhr. 2002 June; 45(3): 53144. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12069005&dopt=Abstract
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Vesiculopustular eruptions in Down syndrome neonates with myeloproliferative disorders. Author(s): Nijhawan A, Baselga E, Gonzalez-Ensenat MA, Vicente A, Southern JF, Camitta BM, Esterly NB, Drolet BA. Source: Archives of Dermatology. 2001 June; 137(6): 760-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11405767&dopt=Abstract
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Weight-correction formula for maternal serum screening for Down syndrome in Taiwan. Author(s): Jou HJ, Wu SC, Lu YM, Liao WC, Hsieh FJ. Source: J Formos Med Assoc. 2000 December; 99(12): 931-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11155747&dopt=Abstract
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When are we allowed to use a marker in Down syndrome screening? Author(s): Farina A, Rizzo N, Carinci P, Bovicelli L. Source: Prenatal Diagnosis. 1999 November; 19(11): 1084-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10589069&dopt=Abstract
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White papules in a child with Down syndrome. Author(s): Galbraith SS, Fairley JA, Esterly NB. Source: Pediatric Dermatology. 2002 May-June; 19(3): 271-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12047651&dopt=Abstract
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Whither Down syndrome critical regions? Author(s): Shapiro BL. Source: Human Genetics. 1997 March; 99(3): 421-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9050934&dopt=Abstract
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Wilms tumor in a child with Down syndrome. Author(s): Kusumakumary P, Ninan M, Chellam VG, Jacob R, Nair MK. Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1995 August; 17(3): 276. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7620928&dopt=Abstract
•
Women with a reduced ovarian complement may have an increased risk for a child with Down syndrome. Author(s): Freeman SB, Yang Q, Allran K, Taft LF, Sherman SL. Source: American Journal of Human Genetics. 2000 May; 66(5): 1680-3. Epub 2000 March 24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733467&dopt=Abstract
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Womens' preference in Down syndrome screening. Author(s): de Graaf IM, Tijmstra T, Bleker OP, van Lith JM. Source: Prenatal Diagnosis. 2002 July; 22(7): 624-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12124700&dopt=Abstract
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Women's preferences for reporting of Down syndrome screening results. Author(s): Mulvey S, Pham T, Tyzack K, Wallace EM. Source: The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2002 November; 42(5): 504-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12495095&dopt=Abstract
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Work stress and people with Down syndrome and dementia. Author(s): Donaldson S. Source: Downs Syndr Res Pract. 2002 September; 8(2): 74-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12407972&dopt=Abstract
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Working memory in children and adolescents with Down syndrome: evidence from a colour memory experiment. Author(s): Laws G. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2002 March; 43(3): 353-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944877&dopt=Abstract
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YAC and cosmid FISH mapping of an unbalanced chromosomal translocation causing partial trisomy 21 and Down syndrome. Author(s): Nadal M, Mila M, Pritchard M, Mur A, Pujals J, Blouin JL, Antonarakis SE, Ballesta F, Estivill X. Source: Human Genetics. 1996 October; 98(4): 460-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8792823&dopt=Abstract
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CHAPTER 2. NUTRITION AND DOWN SYNDROME Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Down syndrome.
Finding Nutrition Studies on Down Syndrome 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 “Down syndrome” (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 “Down syndrome” (or a synonym): •
A murine model for Down syndrome shows reduced responsiveness to pain. Author(s): Department of Physiology and Pharmacology, Faculty of Medicine, University of Cantabria, Santander, Spain. Source: Martinez Cue, C Baamonde, C Lumbreras, M A Vallina, I F Dierssen, M Florez, J Neuroreport. 1999 April 6; 10(5): 1119-22 0959-4965
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Adverse effects of phenytoin given for late-onset seizures in adults with Down syndrome. Author(s): George A. Jervis Clinic, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, New York, NY 10314, USA.
[email protected] Source: Tsiouris, J A Patti, P J Tipu, O Raguthu, S Neurology. 2002 September 10; 59(5): 779-80 0028-3878
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An enzymatic marker in mothers of trisomy 21 children: neutrophil alkaline phosphatase. Author(s): Laboratoire d'Enzymologie, INSERM, CNRS, CHU de Rangueil, Toulouse, France. Source: Vergnes, H Grozdea, J Brisson Lougarre, A Bourrouillou, G Blum, C Martin, J Colombies, P Enzyme. 1988; 39(3): 174-80 0013-9432
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Antioxidant system in Down syndrome: a possible role in cataractogenesis. Author(s): I.U. Cerrahpasa Tip Fakultesi, Genetik ve Teratoloji Uygulama ve Arastirma Merkezi, Cerrahpasa, Istanbul, Turkey.
[email protected] Source: Cengiz, M Seven, M Suyugul, N Genet-Couns. 2002; 13(3): 339-42 1015-8146
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Caring for children with Down syndrome and their families. Author(s): College of Nursing, The Ohio State University, 1585 Neil Ave., Columbus, OH 43210, USA. Source: Van Riper, M Cohen, W I J-Pediatr-Health-Care. 2001 May-June; 15(3): 123-31 0891-5245
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Chromosomal break points in irradiated and ethyl methane sulphonate treated leucocytes of patients with Down syndrome. Author(s): Department of Genetics, Dr A.L.M. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani. Source: Reeja, T C Chandra, N Marimuthu, K M Indian-J-Exp-Biol. 1993 Mar; 31(3): 2015 0019-5189
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Chromosome fragile sites in Down syndrome patients. Author(s): Department of Public Health and Cell Biology, II University of Rome, Italy. Source: Tedeschi, B Vernole, P Caporossi, D Nicoletti, B Am-J-Med-Genet-Suppl. 1990; 7192-4 1040-3787
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Detection of apoptosis in peripheral blood cells of 31 subjects affected by Down syndrome before and after zinc therapy. Author(s): Istituto di Morfologia Umana Normale, Universita G. d'Annunzio, Chieti, Italy. Source: Antonucci, A Di Baldassarre, A Di Giacomo, F Stuppia, L Palka, G UltrastructPathol. 1997 Sep-October; 21(5): 449-52 0191-3123
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DSCR1, overexpressed in Down syndrome, is an inhibitor of calcineurin-mediated signaling pathways. Author(s): Down Syndrome Research Group, Medical and Molecular Genetics Center, IRO, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain.
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Source: Fuentes, J J Genesca, L Kingsbury, T J Cunningham, K W Perez Riba, M Estivill, X de la Luna, S Hum-Mol-Genet. 2000 July 1; 9(11): 1681-90 0964-6906 •
Effects of a single transdermal nicotine dose on cognitive performance in adults with Down syndrome. Author(s): Department of Pediatrics, University of Vienna, Austria. Source: Bernert, G Sustrova, M Sovcikova, E Seidl, R Lubec, G J-Neural-Transm-Suppl. 2001; (61): 237-45 0303-6995
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Ethical issues in emerging new treatments such as growth hormone therapy for children with Down syndrome and Prader-Willi syndrome. Author(s): Rainbow Babies and Childrens Hospital, Cleveland, OH, USA. Source: Kodish, E Cuttler, L Curr-Opin-Pediatr. 1996 August; 8(4): 401-5 1040-8703
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Growth delay in Down syndrome and zinc sulphate supplementation. Author(s): Chair of Endocrinology, University G. D'Annunzio, Chieti, Italy. Source: Napolitano, G Palka, G Grimaldi, S Giuliani, C Laglia, G Calabrese, G Satta, M A Neri, G Monaco, F Am-J-Med-Genet-Suppl. 1990; 763-5 1040-3787
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Growth hormone administration normalizes the ovarian responsiveness to folliclestimulating-hormone in the early stages of the follicular maturation in women with Down syndrome. Author(s): Unita di Ostetricia e Ginecologia, OASI-Istituto Scientifico di Ricovero e Cura, Troina, Enna, Italy. Source: Cento, R M Ragusa, L Proto, C Alberti, A Fiore, G Soranna, L Colabucci, F Lanzone, A J-Endocrinol-Invest. 1998 June; 21(6): 342-7 0391-4097
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Growth hormone therapy for Prader-Willi and Down syndromes: a post-modern medical dilemma. Author(s): Maclean Center for Clinical Medical Ethics, University of Chicago Pritzker School of Medicine, Illinois 60637, USA.
[email protected] Source: Lantos, J D Growth-Horm-IGF-Res. 2000 April; 10 Suppl BS93-4 1096-6374
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Growth hormone therapy in young children with Down syndrome and a clinical comparison of Down and Prader-Willi syndromes. Author(s): Department of Genetics and Pathology, Uppsala University, Sweden.
[email protected] Source: Anneren, G Tuvemo, T Gustafsson, J Growth-Horm-IGF-Res. 2000 April; 10 Suppl BS87-91 1096-6374
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Hematological and biochemical studies in children with Down syndrome. Author(s): Division de Genetica, Hospital de Especialidades del Centro Medico de Occidente, IMSS, Guadalajara, Jalisco, Mexico. Source: Ibarra, B Rivas, F Medina, C Franco, M E Romero Garcia, F Enriquez, C Galarza, M Hernandez Cordova, A Hernandez, T Ann-Genet. 1990; 33(2): 84-7 0003-3995
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High-dose cytosine arabinoside and fractionated total body irradiation as a preparative regimen for the treatment of children with acute lymphoblastic leukemia and Down syndrome by allogeneic bone marrow transplantation. Author(s): Pediatric Hematology Department, University of Milan, S Gerardo Hospital, Monza, Italy. Source: Conter, V D'Angelo, P Rizzari, C Jankovic, M Dampier, C Masera, G Johnson, F L Bone-Marrow-Transplant. 1996 February; 17(2): 287-9 0268-3369
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Hypercalcaemia in association with trisomy 21 (Down's syndrome). Author(s): The Royal Hospital for Sick Children, Glasgow G3 8SJ, UK.
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Source: Ramage, I J Durkan, A Walker, K Beattie, T J J-Clin-Pathol. 2002 July; 55(7): 543-4 0021-9746 •
Impaired cyclic AMP production in the hippocampus of a Down syndrome murine model. Author(s): Department of Physiology and Pharmacology, University of Cantabria Medical School, Santander, Spain. Source: Dierssen, M Vallina, I F Baamonde, C Lumbreras, M A Martinez Cue, C Calatayud, S G Florez, J Brain-Res-Dev-Brain-Res. 1996 August 20; 95(1): 122-4 0165-3806
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Inositol and inositol 1,4,5-trisphosphate content of Down syndrome fibroblasts exhibiting enhanced inositol uptake. Author(s): Department of Genetics, University of Minnesota, Minneapolis 55455. Source: Fruen, B R Lester, B R FEBS-Lett. 1991 December 16; 295(1-3): 43-7 0014-5793
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Is there a relationship between zinc and the peculiar comorbidities of Down syndrome? Author(s): Unita Operativa Autonoma di Pediatria, Oasi Institute (IRCCS), Troina, Italy.
[email protected] Source: Romano, C Pettinato, R Ragusa, L Barone, C Alberti, A Failla, P Downs-SyndrRes-Pract. 2002 March; 8(1): 25-8 0968-7912
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Is zinc deficiency a cause of subclinical hypothyroidism in Down syndrome? Author(s): Chairs of Endocrinology, University G. d'Annunzio, Chieti, Italy. Source: Napolitano, G Palka, G Lio, S Bucci, I De Remigis, P Stuppia, L Monaco, F AnnGenet. 1990; 33(1): 9-15 0003-3995
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Maternal risk factors and major associated defects in infants with Down syndrome. Author(s): California Birth Defects Monitoring Program, Emeryville 94608-1811, USA. Source: Torfs, C P Christianson, R E Epidemiology. 1999 May; 10(3): 264-70 1044-3983
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Plasma carnitine levels in children with Down syndrome. Author(s): Genetik Arastirma Merkezi, Cerrahpasa Tip Fakultesi, Istanbul Universitesi, Cerrahpasa, Istanbul, Turkey.
[email protected] Source: Seven, M Cengiz, M Tuzgen, S Iscan, M Y Am-J-Human-Biol. 2001 NovDecember; 13(6): 721-5 1042-0533
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Protein expression in Down syndrome brain. Author(s): Department of Pediatrics, University of Vienna, Austria. Source: Engidawork, E Lubec, G Amino-Acids. 2001 December; 21(4): 331-61 0939-4451
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Reduction of susceptibility to upper respiratory tract infections in Down syndrome children following treatment with GABAergic drugs: report of 70 cases. Source: Cocchi, R Int-J-Psychosom. 1987; 34(2): 3-7 0884-8297
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Stimulated parotid salivary flow rate in patients with Down syndrome. Author(s): Department of Orthodontics, Hebrew University-Hadassah School of Dental Medicine, Jerusalem, Israel.
[email protected] Source: Chaushu, Stella Becker, Adrian Chaushu, Gabriel Shapira, Joseph Spec-CareDentist. 2002 Jan-February; 22(1): 41-4 0275-1879
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Systematic review of the effect of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome. Author(s): Department of Paediatric Neurosciences, King's College Hospital, London, UK.
[email protected] Source: Salman, M Eur-J-Paediatr-Neurol. 2002; 6(4): 213-9 1090-3798
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Tooth wear in children with Down syndrome. Author(s): Dental School, The University of Adelaide, South Australia. Source: Bell, E J Kaidonis, J Townsend, G C Aust-Dent-J. 2002 March; 47(1): 30-5 00450421
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMDHealth: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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The following is a specific Web list relating to Down syndrome; 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 Zinc Source: Prima Communications, Inc.www.personalhealthzone.com
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CHAPTER 3. SYNDROME
ALTERNATIVE MEDICINE AND DOWN
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Down syndrome. 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 Down syndrome 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 “Down syndrome” (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 Down syndrome: •
A four-year longitudinal study of palatal plate therapy in children with Down syndrome: effects on oral motor function, articulation and communication preferences. Author(s): Carlstedt K, Henningsson G, Dahllof G. Source: Acta Odontologica Scandinavica. 2003 February; 61(1): 39-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12635780&dopt=Abstract
•
Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Author(s): James SJ, Pogribna M, Pogribny IP, Melnyk S, Hine RJ, Gibson JB, Yi P, Tafoya DL, Swenson DH, Wilson VL, Gaylor DW. Source: The American Journal of Clinical Nutrition. 1999 October; 70(4): 495-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10500018&dopt=Abstract
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•
An enzymatic marker in mothers of trisomy 21 children: neutrophil alkaline phosphatase. Author(s): Vergnes H, Grozdea J, Brisson-Lougarre A, Bourrouillou G, Blum C, Martin J, Colombies P. Source: Enzyme. 1988; 39(3): 174-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2454188&dopt=Abstract
•
An evaluation of cell therapy in Down syndrome. Author(s): Foreman PJ, Ward J. Source: Aust Paediatr J. 1987 June; 23(3): 151-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2959248&dopt=Abstract
•
Bimanual coordination dynamics in adults with Down syndrome. Author(s): Robertson Ringenbach SD, Chua R, Maraj BK, Kao JC, Weeks DJ. Source: Motor Control. 2002 October; 6(4): 388-407. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429892&dopt=Abstract
•
Caring for children with Down syndrome and their families. Author(s): Van Riper M, Cohen WI. Source: Journal of Pediatric Health Care : Official Publication of National Association of Pediatric Nurse Associates & Practitioners. 2001 May-June; 15(3): 123-31. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11353361&dopt=Abstract
•
Cell therapy in children with Down syndrome: a retrospective study. Author(s): Van Dyke DC, Lang DJ, van Duyne S, Heide F, Chang HJ. Source: Pediatrics. 1990 January; 85(1): 79-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2136948&dopt=Abstract
•
Concern about Piracetam treatment for children with Down syndrome. Author(s): Holmes LB. Source: Pediatrics. 1999 May; 103(5 Pt 1): 1078-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10357649&dopt=Abstract
•
Context of directives given to young children with Down syndrome and nonretarded children: development over two years. Author(s): Maurer H, Sherrod KB. Source: Am J Ment Defic. 1987 May; 91(6): 579-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2954461&dopt=Abstract
•
Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome.
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Author(s): Zwaan CM, Kaspers GJ, Pieters R, Hahlen K, Janka-Schaub GE, van Zantwijk CH, Huismans DR, de Vries E, Rots MG, Peters GJ, Jansen G, Creutzig U, Veerman AJ. Source: Blood. 2002 January 1; 99(1): 245-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11756178&dopt=Abstract •
Down syndrome and religious groups. Author(s): Jongbloet PH, Poestkoke AJ, Hamers AJ, van Erkelens-Zwets JH. Source: Lancet. 1978 December 16; 2(8103): 1310. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=82812&dopt=Abstract
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Educational/support group for Latino families of children with Down syndrome. Author(s): Shapiro J, Simonsen D. Source: Mental Retardation. 1994 December; 32(6): 403-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7854133&dopt=Abstract
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Effects of nutritional supplementation on IQ and certain other variables associated with Down syndrome. Author(s): Weathers C. Source: Am J Ment Defic. 1983 September; 88(2): 214-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6227244&dopt=Abstract
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Electrodermal orienting activity in children with Down syndrome. Author(s): Martinez-Selva JM, Garcia-Sanchez FA, Florit R. Source: Am J Ment Retard. 1995 July; 100(1): 51-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7546636&dopt=Abstract
•
Enhanced DNA repair in lymphocytes of Down syndrome patients: the influence of zinc nutritional supplementation. Author(s): Chiricolo M, Musa AR, Monti D, Zannotti M, Franceschi C. Source: Mutation Research. 1993 August; 295(3): 105-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7689697&dopt=Abstract
•
Folic acid and Down syndrome. Author(s): Trissler RJ. Source: Journal of the American Dietetic Association. 2000 February; 100(2): 159. Erratum In: J Am Diet Assoc 2000 May; 100(5): 516. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10691390&dopt=Abstract
•
Growth delay in Down syndrome and zinc sulphate supplementation. Author(s): Napolitano G, Palka G, Grimaldi S, Giuliani C, Laglia G, Calabrese G, Satta MA, Neri G, Monaco F. Source: Am J Med Genet Suppl. 1990; 7: 63-5.
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http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2149976&dopt=Abstract •
Health care management of adults with Down syndrome. Author(s): Smith DS. Source: American Family Physician. 2001 September 15; 64(6): 1031-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11578024&dopt=Abstract
•
Hearing abilities of Down syndrome and other mentally handicapped adolescents. Author(s): Marcell MM, Cohen S. Source: Research in Developmental Disabilities. 1992 November-December; 13(6): 53351. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1480804&dopt=Abstract
•
High-dose cytosine arabinoside and fractionated total body irradiation as a preparative regimen for the treatment of children with acute lymphoblastic leukemia and Down syndrome by allogeneic bone marrow transplantation. Author(s): Conter V, D'Angelo P, Rizzari C, Jankovic M, Dampier C, Masera G, Johnson FL. Source: Bone Marrow Transplantation. 1996 February; 17(2): 287-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8640182&dopt=Abstract
•
Improving the classroom listening skills of children with Down syndrome by using sound-field amplification. Author(s): Bennetts LK, Flynn MC. Source: Downs Syndr Res Pract. 2002 March; 8(1): 19-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11915433&dopt=Abstract
•
In vivo folic acid supplementation partially corrects in vitro methotrexate toxicity in patients with Down syndrome. Author(s): Peeters MA, Rethore MO, Lejeune J. Source: British Journal of Haematology. 1995 March; 89(3): 678-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7734380&dopt=Abstract
•
Increased plasma and erythrocyte selenium concentrations but decreased erythrocyte glutathione peroxidase activity after selenium supplementation in children with Down syndrome. Author(s): Anneren G, Gebre-Medhin M, Gustavson KH. Source: Acta Paediatr Scand. 1989 November; 78(6): 879-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2532445&dopt=Abstract
•
Intracranial germ cell tumors in children with and without Down syndrome. Author(s): Chik K, Li C, Shing MM, Leung T, Yuen PM.
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Source: Journal of Pediatric Hematology/Oncology : Official Journal of the American Society of Pediatric Hematology/Oncology. 1999 March-April; 21(2): 149-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10206462&dopt=Abstract •
KAP study on mothers of children with Down syndrome. Author(s): Lakshminarayana P, Ibrahim S, Venkataraman P, Jagatheesan T, Kamala KG. Source: Indian Pediatrics. 1991 September; 28(9): 997-1001. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1839390&dopt=Abstract
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Long-term effects of palatal plate therapy on oral motor function in children with Down syndrome evaluated by video registration. Author(s): Carlstedt K, Henningsson G, McAllister A, Dahllof G. Source: Acta Odontologica Scandinavica. 2001 April; 59(2): 63-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11370751&dopt=Abstract
•
Nutritional supplementation in Down syndrome: theoretical considerations and current status. Author(s): Ani C, Grantham-McGregor S, Muller D. Source: Developmental Medicine and Child Neurology. 2000 March; 42(3): 207-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10755461&dopt=Abstract
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Point-of-care time-resolved immunofluorometric assay for human pregnancyassociated plasma protein A: use in first-trimester screening for Down syndrome. Author(s): Qin QP, Christiansen M, Pettersson K. Source: Clinical Chemistry. 2002 March; 48(3): 473-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11861437&dopt=Abstract
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Prognostic factors in children and adolescents with acute myeloid leukemia (excluding children with Down syndrome and acute promyelocytic leukemia): univariate and recursive partitioning analysis of patients treated on Pediatric Oncology Group (POG) Study 8821. Author(s): Chang M, Raimondi SC, Ravindranath Y, Carroll AJ, Camitta B, Gresik MV, Steuber CP, Weinstein H. Source: Leukemia : Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2000 July; 14(7): 1201-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10914543&dopt=Abstract
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Reflex seizures in Down syndrome. Author(s): Pueschel SM, Louis S. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 1993 February; 9(1): 23-4.
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http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8481939&dopt=Abstract •
Short-term efficacy of thyroid hormone supplementation for patients with Down syndrome and low-borderline thyroid function. Author(s): Tirosh E, Taub Y, Scher A, Jaffe M, Hochberg Z. Source: Am J Ment Retard. 1989 May; 93(6): 652-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2524203&dopt=Abstract
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Spontaneous stereotypy in an animal model of Down syndrome: Ts65Dn mice. Author(s): Turner CA, Presti MF, Newman HA, Bugenhagen P, Crnic L, Lewis MH. Source: Behavior Genetics. 2001 July; 31(4): 393-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11720125&dopt=Abstract
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Strabismus and binocular function in children with Down syndrome. A populationbased, longitudinal study. Author(s): Haugen OH, Hovding G. Source: Acta Ophthalmologica Scandinavica. 2001 April; 79(2): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11284750&dopt=Abstract
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Study of spindle microtubule reassembly in cells from Alzheimer and Down syndrome patients following exposure to colcemid. Author(s): Krawczun MS, Jenkins EC, Lele KP, Sersen EA, Wisniewski HM. Source: Alzheimer Disease and Associated Disorders. 1990 Winter; 4(4): 203-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2148262&dopt=Abstract
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Systematic review of the effect of therapeutic dietary supplements and drugs on cognitive function in subjects with Down syndrome. Author(s): Salman M. Source: European Journal of Paediatric Neurology : Ejpn : Official Journal of the European Paediatric Neurology Society. 2002; 6(4): 213-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12374588&dopt=Abstract
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The effect of mitotic inhibitors on DNA strand size and radiation-associated break repair in Down syndrome fibroblasts. Author(s): Woods WG, Steiner ME, Kalvonjian SL. Source: Biochimica Et Biophysica Acta. 1985 March 20; 824(3): 177-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3155969&dopt=Abstract
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Theory of mind abilities in individuals with autism, Down syndrome, and mental retardation of unknown etiology: the role of age and intelligence. Author(s): Yirmiya N, Solomonica-Levi D, Shulman C, Pilowsky T. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1996 November; 37(8): 1003-14.
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http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9119934&dopt=Abstract •
Trisomy 21 associated transient neonatal myeloproliferation in the absence of Down's syndrome. Author(s): Richards M, Welch J, Watmore A, Readett D, Vora AJ. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 1998 November; 79(3): F215-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10194996&dopt=Abstract
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Use of megadoses of vitamins with minerals in Down syndrome. Author(s): Smith GF, Spiker D, Peterson CP, Cicchetti D, Justine P. Source: The Journal of Pediatrics. 1984 August; 105(2): 228-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6235336&dopt=Abstract
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Very low alpha-fetoprotein in Down syndrome maternal serum screening. Author(s): Muller F, Dreux S, Sault C, Galland A, Puissant H, Couplet G, Lemay C, Larcher ME, Renom G; ABA Group. Source: Prenatal Diagnosis. 2003 July; 23(7): 584-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12868089&dopt=Abstract
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Vitamin therapy and children with Down syndrome: a review of research. Author(s): Pruess JB, Fewell RR, Bennett FC. Source: Except Child. 1989 January; 55(4): 336-41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2521601&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/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMDHealth: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to Down syndrome; 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 Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Leukemia Source: Integrative Medicine Communications; www.drkoop.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON DOWN SYNDROME Overview In this chapter, we will give you a bibliography on recent dissertations relating to Down syndrome. 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 “Down syndrome” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Down syndrome, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Down Syndrome 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 Down syndrome. 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: •
A Case Analysis of Three Middle-school Boys Who Have Down Syndrome and Have Been in Regular Education Classes since Preschool by Luddy, Eileen Frances; Phd from Andrews University, 2002, 257 pages http://wwwlib.umi.com/dissertations/fullcit/3058310
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A Comparative Analysis of Playground Peer Interactions of Children with Down Syndrome by Terry-gage, Susann, Phd from University of California, Los Angeles, 1998, 90 pages http://wwwlib.umi.com/dissertations/fullcit/9906219
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A Comparative Study of the Conversational Skills of Fragile-x, Autistic, and Down Syndrome Individuals by Ferrier, Linda J., Phd from Boston University, 1987, 225 pages http://wwwlib.umi.com/dissertations/fullcit/8715419
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A Comparison of the Influence of Maternal Empathy, Child's Independence Skills, and Perceived Social Support, on Parenting Practices of Mothers of Preschool Children with Down Syndrome and Mothers of Preschool Children without
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Disabilities by Garcia-tunon, Aurora Amelia, Phd from New York University, 1997, 147 pages http://wwwlib.umi.com/dissertations/fullcit/9737461 •
A Comparison of the Language, Turn-taking and Gaze Behavior of Down Syndrome and Nonretarded Child-mother Dyads by Brand, Judith Patricia, Phd from Fordham University, 1989, 132 pages http://wwwlib.umi.com/dissertations/fullcit/9007172
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A Descriptive Analysis of Friendship in Children with Down Syndrome by Freeman, Stephanny Fumi Noro, Phd from University of California, Los Angeles, 1997, 88 pages http://wwwlib.umi.com/dissertations/fullcit/9803548
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A Descriptive Study of Visual Behaviors of Children with Down Syndrome by Welsch, Marie Jeanne, Phd from The University of Texas at Austin, 1985, 221 pages http://wwwlib.umi.com/dissertations/fullcit/8609447
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A Handbook on Down Syndrome for School Psychologists by Vicari Appleheimer, Annette E., Psyd from Rutgers the State University of New Jersey, G.s.a.p.p., 1990, 129 pages http://wwwlib.umi.com/dissertations/fullcit/9033376
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A Microgenetic Comparison of Maternal Scaffolding Strategies during Joint Bookreading by Mothers of Children with and without Down Syndrome by Bair, Pauline Helen, Phd from University of Illinois at Urbana-champaign, 1997, 130 pages http://wwwlib.umi.com/dissertations/fullcit/9737040
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A Neuropsychological Model for the Development of the Cognitive Profiles in Mental Retardation Syndromes: Evidence from Down Syndrome and Williams Syndrome by Edgin, Jamie Ogline; Phd from University of Denver, 2003, 91 pages http://wwwlib.umi.com/dissertations/fullcit/3086381
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A Vibratory System Analysis of Motor Control in Selected Down Syndrome Subjects by Davis, Walter E., Phd from The University of Connecticut, 1980, 172 pages http://wwwlib.umi.com/dissertations/fullcit/8106699
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An Analysis of the Effects of Visual and Somatosensory-vestibular Input on the Postural Reactions of Infants Having Down Syndrome (physical Therapy) by Effgen, Susan K., Phd from Georgia State University, 1984, 151 pages http://wwwlib.umi.com/dissertations/fullcit/8417130
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An Approach to Identify Genes Involved in Trisomy-associated Phenotypes: Application to Atrioventricular Septal Defects in Down Syndrome by Kerstann, Kimberly Fowler; Phd from Emory University, 2003, 149 pages http://wwwlib.umi.com/dissertations/fullcit/3080334
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An Efficacy Study: the Influence of Early Intervention on the Subsequent School Placements of Children with Down Syndrome by Wybranski, Nancy Ann Mcgowan, Edd from Widener University, 1996, 152 pages http://wwwlib.umi.com/dissertations/fullcit/9701172
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An Ethnographic Study of the Inclusive Education of David, a Child with Down Syndrome by Tibbs, Kathleen; Edd from University of Missouri - Saint Louis, 2000, 233 pages http://wwwlib.umi.com/dissertations/fullcit/9961999
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An Exploration of the Separation-individuation Processes in the Down Syndrome Child by Peterson, Karen Lee, Phd from Smith College School for Social Work, 1984, 371 pages http://wwwlib.umi.com/dissertations/fullcit/8417620
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An Investigation of the Relative Effects of Blocked and Random Practice on the Learning of Ballistic Motor Skills in Typically Developing Children and Children with Down Syndrome by Baker, Bruce James; Phd from University of Washington, 2002, 115 pages http://wwwlib.umi.com/dissertations/fullcit/3072055
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And then Came John: an Ethnographic Case Study of the Roles Played by Community and Culturation in the Creation of an 'abnormal' or 'deviant' Human Being (down Syndrome, Mentally Retarded) by Andrews, Scott S., Phd from Stanford University, 1989, 179 pages http://wwwlib.umi.com/dissertations/fullcit/8925822
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Assessing the Impact of a Swimming Intervention Program on Speech Production in Adolescents with Down Syndrome by Casey, Amanda Faith; Msc from University of Calgary (canada), 2002, 97 pages http://wwwlib.umi.com/dissertations/fullcit/MQ76205
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Assessment of Down Syndrome Children: Mullen Scales of Early Learning by Chiodo, Angela A. Psyd from Carlos Albizu University, 2002, 68 pages http://wwwlib.umi.com/dissertations/fullcit/3077969
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Assessments, Goals, and Expectations of Mothers of Children with Down Syndrome Enrolled in Early Intervention Programs by Jameson-bloom, Christina, Phd from Brandeis U., the F. Heller Grad. Sch. for Adv. Stud. in Soc. Wel., 1980, 364 pages http://wwwlib.umi.com/dissertations/fullcit/8112866
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Attachment Behaviors and the Development of the Concept of Permanence in Young Children with Down Syndrome by Morecki-oberg, Carol, Phd from The Claremont Graduate University, 1984, 264 pages http://wwwlib.umi.com/dissertations/fullcit/8407461
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Attitudes of High School Seniors toward Individuals with Mental Retardation and Down Syndrome Following Participation in a Social Integration Friendship Program: an Exploratory Study by Glenn, Anthony T. Edd from Wilmington College (delaware), 2001, 164 pages http://wwwlib.umi.com/dissertations/fullcit/3004825
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Attitudes of Parents in the United States toward Facial Reconstructive Surgery for Children with Down Syndrome by Tenicki, Cynthia Potter, Edd from Columbia University Teachers College, 1994, 242 pages http://wwwlib.umi.com/dissertations/fullcit/9432583
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Atypical Patterns of Release from Proactive Interference As Cognitive Indicators of Dementia of the Alzheimer Type in Adults with Down Syndrome by Calnen, Terrence, Edd from Columbia University Teachers College, 1999, 237 pages http://wwwlib.umi.com/dissertations/fullcit/9921382
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Behavioral Transitions in Children with Autism Compared to Children with Down Syndrome in Their Natural Habitats by Brown, Shannon Ann; Phd from Indiana University, 2002, 159 pages http://wwwlib.umi.com/dissertations/fullcit/3038606
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Beliefs about Maternal Roles and Developmental Benefits in Parent-infant Play Contexts: Learning from Taiwanese Mothers of Children with Down Syndrome by Chen, Yu-jun; Phd from University of Illinois at Urbana-champaign, 2001, 155 pages http://wwwlib.umi.com/dissertations/fullcit/3017041
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Children with Down Syndrome: an Epidemiological Study with Special Focus on Congenital Heart Defects by Frid, Christina Ebba; Phd from Uppsala Universitet (sweden), 2003, 62 pages http://wwwlib.umi.com/dissertations/fullcit/f113889
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Cognitive and Behavioral Effects of Obstructive Sleep Apnea in Toddlers with Down Syndrome by Gaither, Rebecca Ann; Phd from Illinois Institute of Technology, 2003, 49 pages http://wwwlib.umi.com/dissertations/fullcit/3087837
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Computer-assisted Language Intervention: Production, Content, and Modality Effects in Children with Down Syndrome by Archer, Diane Elizabeth (anne), Phd from University of Toronto (canada), 1996, 213 pages http://wwwlib.umi.com/dissertations/fullcit/NN11661
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Coping in Families with a Child Who Has Down Syndrome: a Grounded Theory Study by Shrouf, Ellen Marie, Phd from The University of Texas at Austin, 1997, 196 pages http://wwwlib.umi.com/dissertations/fullcit/9803025
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Creation and Use of Mouse Models to Understand Gene Action in Down Syndrome by Olson, Lisa Erin; Phd from The Johns Hopkins University, 2003, 129 pages http://wwwlib.umi.com/dissertations/fullcit/3080739
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Demographic Trends of Down Syndrome in the State of North Dakota from 1960-1964 to 1980-1984 (maternal, Paternal Age, Gender) by Butts, Carol Sue, Edd from University of Northern Colorado, 1986, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8621956
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Development in Down Syndrome and Normal Infants Attention, Exploration and Environmental Responsivity by Gerrior, Patricia Farrell; Phd from Simon Fraser University (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL48770
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Development of Fundamental Motor Skills in Down Syndrome Preschool Children by Kurz-mcpherson, Karen Ann, Edd from West Virginia University, 1988, 264 pages http://wwwlib.umi.com/dissertations/fullcit/8905119
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Evaluating an Interpersonal Model of Depression with Adults with Down Syndrome by Ailey, Sarah Herrink; Phd from University of Illinois at Chicago, Health Sciences Center, 2002, 152 pages http://wwwlib.umi.com/dissertations/fullcit/3058228
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Family Environment and Coping Strategies of Parents Who Have a Child with Down Syndrome (down Syndrome) by Axelrod, Alice Ann, Edd from Boston University, 1991, 157 pages http://wwwlib.umi.com/dissertations/fullcit/9120020
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Family Functioning of Children with Down Syndrome. by Daniels, Jean Ellen, Dsw from University of California, Los Angeles, 1976, 250 pages http://wwwlib.umi.com/dissertations/fullcit/7701621
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Family Interaction and the School-based Competence of Children with Down Syndrome by Abery, Brian Hinton, Phd from University of Minnesota, 1988, 228 pages http://wwwlib.umi.com/dissertations/fullcit/8907362
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Genetic Basis of Down Syndrome: Physical, Comparative, and Molecular Analysis of Chromosome 21 by Pletcher, Mathew Tyler; Phd from The Johns Hopkins University, 2002, 184 pages http://wwwlib.umi.com/dissertations/fullcit/3046533
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Interaction of Down Syndrome Toddlers and Their Mothers: a Comparative Study with a Chinese Population by Wang, Tien-miau, Phd from The University of North Carolina at Chapel Hill, 1989, 116 pages http://wwwlib.umi.com/dissertations/fullcit/9002447
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Interdigit Force Coordination in Visually Guided Pinch: Studies of Dynamic Isometric Pinch Control in Adults, Typically Developing Children, and Adolescents with Down Syndrome by Moerchen, Victoria Ann; Phd from The University of Wisconsin - Madison, 2002, 258 pages http://wwwlib.umi.com/dissertations/fullcit/3060481
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Lateralization of Speech Perception and Knowledge of Number Concepts in Adolescents with Down Syndrome by Mcnamara, Andrew William; Phd from University of Toronto (canada), 2001, 249 pages http://wwwlib.umi.com/dissertations/fullcit/NQ63671
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Literacy Behaviors of Two First-grade Children with Down Syndrome (inclusion) by Wright, Sarah, Phd from Texas Woman's University, 1995, 283 pages http://wwwlib.umi.com/dissertations/fullcit/9615503
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Maternal Attitude and Adjustment: a Look at Mothers of Twins; One Child with Down Syndrome and One Child with Normal Development by Schumacher, Alison, Edd from Temple University, 1993, 88 pages http://wwwlib.umi.com/dissertations/fullcit/9316527
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Mother-child Interaction: Scaffolded Instruction and the Learning of Problem-solving Skills in Children with Down Syndrome (down Syndrome) by D'amico, Miranda, Phd from Mcgill University (canada), 1991, 179 pages http://wwwlib.umi.com/dissertations/fullcit/NN72139
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Mother-infant Interaction in Relation to the Onset of Intentional Communication: Infants with and without Down Syndrome by Gallagher, Diane L., Phd from Temple University, 1995, 208 pages http://wwwlib.umi.com/dissertations/fullcit/9535743
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Mother-infant Interactions with Normal and Down Syndrome Infants by Markowitz, Susan L., Phd from University of California, Los Angeles, 1980, 157 pages http://wwwlib.umi.com/dissertations/fullcit/8102858
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Mothers' Attributions of Causality for the Birth of a Child with Down Syndrome by Harvey-yoder, Jaye Fulton, Edd from Memphis State University, 1989, 87 pages http://wwwlib.umi.com/dissertations/fullcit/8921994
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Motor Control Strategies Using Feedback and Motor Programs in Young Children with Down Syndrome by Harris, Daslyn Elaine E., Phd from The University of Toledo, 1995, 102 pages http://wwwlib.umi.com/dissertations/fullcit/9540366
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Motor Skill Development of Children with Down Syndrome by Passarini, John Richard; Edd from Boston University, 2001, 264 pages http://wwwlib.umi.com/dissertations/fullcit/3002605
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Object Permanence and Expressive Language Skills in Visually Typical, Visually Atypical and Down Syndrome Infants (uzgiris-hunt, Assessment) by Tulloch, Deborah, Edd from Columbia University Teachers College, 1985, 134 pages http://wwwlib.umi.com/dissertations/fullcit/8525531
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Parent Education and Support Within a Developmental Perspective: a Program Design for the Down Syndrome of Louisville (kentucky) by Williams, Jennifer Louise; Psyd from Spalding University, 2003, 123 pages http://wwwlib.umi.com/dissertations/fullcit/3076347
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Patterns of Play: the Deployment of Attention of Children with and without Down Syndrome during Unstructured Play by Linn, Margaret Inman, Phd from University of Pennsylvania, 1995, 184 pages http://wwwlib.umi.com/dissertations/fullcit/9615078
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Positive Self-evaluation in Young Children with Down Syndrome in Achievement Settings by Hughes, Margaret Ann, Phd from University of California, Los Angeles, 1993, 125 pages http://wwwlib.umi.com/dissertations/fullcit/9329979
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Predictors of Normalized Work for Adults with Down Syndrome by Adams, Patricia B., Jr., Phd from University of California, Los Angeles, 1998, 131 pages http://wwwlib.umi.com/dissertations/fullcit/9906205
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Psychological Distress and Cognitive Coping Processes in Parents of Infants with Down Syndrome by Scott, Brian S; Phd from University of Windsor (canada), 1988 http://wwwlib.umi.com/dissertations/fullcit/NL48178
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Reduction of Stigma toward Children with Down Syndrome Through Inclusion by Liffick, Gregory Gene; Phd from University of California, Los Angeles, 1999, 80 pages http://wwwlib.umi.com/dissertations/fullcit/9940509
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Relationship between Postural Reactions and Motor Milestones in Infants with Down Syndrome by Haley, Stephen Moler, Phd from University of Washington, 1983, 145 pages http://wwwlib.umi.com/dissertations/fullcit/8326873
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Short-term Memory Skills in Down Syndrome and Non-down Children and Adults by Fejes-mendoza, Kathy E., Phd from Arizona State University, 1987, 108 pages http://wwwlib.umi.com/dissertations/fullcit/8713655
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Siblings As Communication Trainers for Prelinguistic Infants with Down Syndrome by Richard, Nancy Barton, Phd from University of Washington, 1987, 241 pages http://wwwlib.umi.com/dissertations/fullcit/8713401
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Siblings of Children with Down Syndrome and Their Perceptions of Family Functioning by Sullivan, Molly Blake; Ms from Texas Woman's University, 2002, 71 pages http://wwwlib.umi.com/dissertations/fullcit/1410095
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Socio-affective and Behavioural Changes in Alzheimer Dementia: Comparing Individuals with and without Down Syndrome by Temple, Valerie Karen; Phd from University of Guelph (canada), 2002, 174 pages http://wwwlib.umi.com/dissertations/fullcit/NQ67240
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Spatial Memory Abilities and Abnormal Development of the Hippocampal Formation in Down Syndrome by Mangan, Peter Anthony, Phd from The University of Arizona, 1992, 139 pages http://wwwlib.umi.com/dissertations/fullcit/9223567
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Stress Experience in Parents Raising a Child with Down Syndrome As Related to the Child's Transitional Developmental Period, Parents' Appraisal of the Child's Handicapping Condition, and Their Personal Coping and Social Resources by Zajicek-farber, Michaela L., Dsw from The Catholic University of America, 1990, 267 pages http://wwwlib.umi.com/dissertations/fullcit/9027644
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Stress, Social Support, and Sense of Parenting Competence: a Comparison of Mothers and Fathers of Children with Autism, Down Syndrome, and Normal Development across the Family Life Cycle by Belchic, Jill Kimberly, Phd from Rutgers the State University of New Jersey - New Brunswick, 1995, 67 pages http://wwwlib.umi.com/dissertations/fullcit/9618823
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Survival of the Fittest: Treatment Issues Involving Newborns with Mental and Physical Handicaps Especially Down Syndrome and Spina Bifida (mental Handicaps, Medical Ethics) by Haunss, Charles Edward, Edd from Columbia University Teachers College, 1991, 103 pages http://wwwlib.umi.com/dissertations/fullcit/9210537
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Swedish Parents of Children with Down Syndrome: a Study on the Initial Information and Support, and the Subsequent Daily Life by Hedov, Gerth; Phd from Uppsala Universitet (sweden), 2002, 53 pages http://wwwlib.umi.com/dissertations/fullcit/f661601
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Temperament in Children with Down Syndrome by Ratekin, Cynthia Sue, Phd from University of California, Los Angeles, 1990, 126 pages http://wwwlib.umi.com/dissertations/fullcit/9111331
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Temporal Processing of Phonated Pitch Pattern Stimuli in Individuals with Down Syndrome (music) by Buckwell, Patricia Jordan, Phd from The University of Toledo, 1986, 162 pages http://wwwlib.umi.com/dissertations/fullcit/8708648
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The Effects of Various Types of Verbal Feedback on the Performance of Selected Motor Development Skills of Adolescent Males with Down Syndrome by Santini Rivera, Mariano, Phd from New York University, 1998, 150 pages http://wwwlib.umi.com/dissertations/fullcit/9832765
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The Influence of the Use of Different Didactic Strategies in the General Performance from the Student with Down Syndrome (spanish Text) by Liesa Orus, Marta; Dr from Universidad De Zaragoza (spain), 2002, 840 pages http://wwwlib.umi.com/dissertations/fullcit/3076282
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The Mother-child Communicative Interactions of Educationally Advantaged Down Syndrome and Normal Children Matched for Auditory Comprehension (language, Speech, Mental Retardation) by Horstmeier, Deanna Smith, Phd from The Ohio State University, 1985, 127 pages http://wwwlib.umi.com/dissertations/fullcit/8603008
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The Prevention and Remediation of Down Syndrome by Piper, Martha C; Phd from Mcgill University (canada), 1979 http://wwwlib.umi.com/dissertations/fullcit/NK42999
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The Relation between Speaking Rate and Verbal Short-term Memory in Individuals with Down Syndrome by Seung, Hye-kyeung, Phd from The University of Wisconsin Madison, 1998, 192 pages http://wwwlib.umi.com/dissertations/fullcit/9825755
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The Relation of Maternal Style and the Language Development of Children with Down Syndrome by Harris, Sharon Sachiko, Phd from University of California, Los Angeles, 1994, 105 pages http://wwwlib.umi.com/dissertations/fullcit/9431180
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The Role of Temperament and Emotion Regulation in the Social Adjustment of Children with Fragile X Syndrome and Down Syndrome by Urv, Tiina Karin, Phd from Columbia University, 1998, 206 pages http://wwwlib.umi.com/dissertations/fullcit/9910672
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The Social Representation of Children with Down Syndrome: an Interpretivist Analysis by Kliewer, Christopher Lee, Phd from Syracuse University, 1995, 395 pages http://wwwlib.umi.com/dissertations/fullcit/9620103
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The Talk of Mothers and Their Children with and without Down Syndrome While Reading Scripted and Nonscripted Picture Books by Allen, Jennifer M. Msc from Dalhousie University (canada), 2002, 121 pages http://wwwlib.umi.com/dissertations/fullcit/MQ75434
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Use of Part I of the Adaptive Behavior Scale in the Assessment of Dementia: Detection of Suspected Alzheimer-like Brain Changes in Persons with Down Syndrome Through Adaptive Behavior Measurement (dementia Assessment) by Tucker, Michael Barton, Edd from Columbia University Teachers College, 1992, 184 pages http://wwwlib.umi.com/dissertations/fullcit/9306316
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Utilizing Group Art Therapy to Enhance the Social Skills of Children with Autism and Down Syndrome by Kanareff, Rita Lynn; Ma from Ursuline College, 2002, 182 pages http://wwwlib.umi.com/dissertations/fullcit/1408034
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 TRIALS AND DOWN SYNDROME Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Down syndrome.
Recent Trials on Down Syndrome The following is a list of recent trials dedicated to Down syndrome.8 Further information on a trial is available at the Web site indicated. •
Chemotherapy in Treating Children With Down Syndrome Plus Myeloproliferative Disorder, Acute Myelogenous Leukemia, or Myelodysplastic Syndrome Condition(s): atypical chronic myeloid leukemia; childhood acute monocytic leukemia; childhood acute myeloid leukemia and other myeloid malignancies; Essential Thrombocythemia; myelodysplastic and myeloproliferative disease Study Status: This study is currently recruiting patients. Sponsor(s): Children's Oncology Group; National Cancer Institute (NCI) Purpose - Excerpt: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase III trial to study the effectiveness of combination chemotherapy in treating children who have Down syndrome plus myeloproliferative disorder, acute myelogenous leukemia, or myelodysplastic syndrome. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00003593
8
These are listed at www.ClinicalTrials.gov.
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•
Vitamin E in Aging Persons With Down Syndrome Condition(s): Down Syndrome; Alzheimer Disease Study Status: This study is currently recruiting patients. Sponsor(s): National Institute on Aging (NIA); National Institute of Child Health and Human Development (NICHD); National Center for Complementary and Alternative Medicine (NCCAM) Purpose - Excerpt: The goal of this study is to determine the safety and efficacy of the administration of vitamin E, which has been shown to delay the progression of Alzheimer's disease, in slowing the rate of cognitive/functional decline in older persons with Down syndrome. Phase(s): Phase III Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00056329
•
Down Syndrome - Comparison of Screening Methods in the 1st and 2nd Trimesters Condition(s): Down Syndrome; Chromosome Abnormalities Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Child Health and Human Development (NICHD) Purpose - Excerpt: Too much or too little genetic information (chromosome material) can cause abnormal development of the fetus or death. Each year approximately 2.5 million pregnant women are screened for Down Syndrome using invasive screening methods (amniocentesis or chorionic villus sampling). This 11 center study of 38,000 women will compare the accuracy of the several non-invasive tests in the first and second trimesters of pregnancy versus amniocentesis or diagnosis at birth to diagnose aneuploidy or Down Syndrome. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006445
•
Reproduction and Survival After Cardiac Defect Repair Condition(s): Cardiovascular Diseases; Heart Diseases; Defect, Congenital Heart; Aortic Valve Stenosis; Transposition of Great Vessels; Ductus Arteriosus, Patent; Heart Septal Defects, Atrial; Heart Septal Defects, Ventricular; Down Syndrome; Tetralogy of Fallot; Pulmonic stenosis; Coarctation of aorta Study Status: This study is completed. Sponsor(s): National Heart, Lung, and Blood Institute (NHLBI) Purpose - Excerpt: To create a registry of all Oregon children undergoing surgical repair of congenital heart disease since 1958 in order to determine mortality, morbidity, and disability after surgery and to assess the safety of pregnancy in women with corrected congenital heart disease and the risk of prematurity and occurrence of congenital heart defects in offspring. Study Type: Observational Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00005190
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 “Down syndrome” (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/
•
For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
•
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/
•
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. PATENTS ON DOWN SYNDROME 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 “Down syndrome” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Down syndrome, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Down Syndrome By performing a patent search focusing on Down syndrome, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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The following is an example of the type of information that you can expect to obtain from a patent search on Down syndrome: •
Crossed immunoelectrophoretic occurrence
technique
for
predicting
Down's
syndrome
Inventor(s): Kerkay; Julius (8040 Barbara Dr., Strongsville, OH 44136) Assignee(s): none reported Patent Number: 4,818,708 Date filed: May 21, 1985 Abstract: An improved crossed electrophoretic technique is disclosed, which is especially adapted for detecting the presence in serum of a protein associated with parenting a Down's syndrome child. The improved technique comprises reducing the second dimension gel antiserum concentration and increasing the second dimension voltage, to be within certain limits. Excerpt(s): This invention relates to prediction and diagnosis by assay of blood serum proteins. In particular, it relates to a crossed immunoelectrophoretic technique for detecting the presence in serum of a protein associated with parenting a Down's syndrome child. Down's syndrome, the major cause of congenital mental retardation, is also the most common birth defect in man. It was traditionally called "mongolism", a name which has fallen from favor. In addition to the more modern name, Down's syndrome, this anomaly is often referred to as trisomy 21. Whereas "Down's syndrome" is used to describe those individuals who present certain clinical features, the term, trisomy 21, refers to the presumed chromosomal basis for these features. Over 90 percent of the individuals affected with Down's syndrome have an extra number 21 chromosome in their cells. Trisomy 21 results from nondisjunction or failure of chromosomes to separate sometime during either division of meiosis or mitosis. Most Down's syndrome individuals have trisomy 21, and conversely, in individuals who carry a translocation involving chromosome 21, and in mosaics who have both trisomic and normal cells, the characteristics of the syndrome are seen. Web site: http://www.delphion.com/details?pn=US04818708__ •
Diagnostic test for prenatal identification of Down's syndrome and mental retardation and gene therapy therefor Inventor(s): Rubin; Edward M. (Berkeley, CA), Smith; Desmond J. (Oakland, CA) Assignee(s): The Regents of the University of California (Oakland, CA) Patent Number: 6,100,033 Date filed: April 30, 1998 Abstract: A a diagnostic test useful for prenatal identification of Down syndrome and mental retardation. A method for gene therapy for correction and treatment of Down syndrome. DYRK gene involved in the ability to learn. A method for diagnosing Down's syndrome and mental retardation and an assay therefor. A pharmaceutical composition for treatment of Down's syndrome mental retardation. Excerpt(s): This invention concerns a diagnostic test useful for prenatal identification of Down syndrome and mental retardation and a gene therapy for correction and
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treatment thereof. In particular, this invention concerns identification of DYRK gene involved in the ability to learn. The invention further concerns a method for diagnosing Down's syndrome and mental retardation and an assay therefor, a method for gene therapy of Down's syndrome and a pharmaceutical composition for treatment of Down's syndrome mental retardation. Down syndrome occurs in about one out of every 800 newborns, with the incidence increasing markedly in the offspring of women over 35. Affecting an estimated one million Americans, it is the leading genetic cause of mental retardation and is associated with a shorter than average life expectancy. Other symptoms are heart and intestinal defects, problems with the immune and endocrine systems, and raft of tissue and skeletal deformities. Individuals with Down syndrome carry a complete extra copy of chromosome 21 in all of their cells, giving each cell a total of 47 chromosomes rather than the normal 46. For this reason, the condition is also known as "Trisomy 21". There are, however, rare forms of Down syndrome in which only part of chromosome 21 is present in triplicate. Web site: http://www.delphion.com/details?pn=US06100033__ •
Down syndrome screening method utilizing dried blood samples Inventor(s): Macri; James N. (170 Sidney St., Oyster Bay, NY 11771) Assignee(s): none reported Patent Number: 5,252,489 Date filed: August 7, 1992 Abstract: The present invention relates to a method for detecting fetal Down syndrome (Trisomy 21), trisomy 13, trisomy 18 and other chromosomal anomalies during prenatal screening by analyzing a dried blood sample from a pregnant woman. More particularly the present invention relates to a method for improving detection efficiency in screening for the anomalies by measuring the amount of the free beta human chorionic gonadotropin (HCG) and nicked or fragmented or aberrant forms of free beta (HCG), all of which are referenced throughout this application as free beta (HCG) in dried blood samples from pregnant women. Excerpt(s): The present invention relates to a method for detecting fetal Down syndrome (Trisomy 21), trisomy 13, trisomy 18, Turners syndrome and other chromosomal anomalies during prenatal screening by analyzing a dried blood sample from a pregnant woman. More particularly the present invention relates to a method for improving detection efficiency in prenatal screening for Down syndrome by measuring the amount of free beta (human chorionic gonadotropin "HCG") and nicked or fragmented or aberrant forms of free beta (HCG) all of which are referenced throughout this application as free beta (HCG) in dried blood samples from pregnant women. Down syndrome, also referred to as Trisomy 21, is the most common congenital cause of severe mental retardation. Generally, fetal Down syndrome can be determined by diagnostic procedures including amniocentesis or chorionic villus sampling and karyotyping. However, these diagnostic procedures are invasive and involve risk to the woman and the fetus. For this and other reasons, amniocentesis or chorionic villus sampling and karyotyping are not routinely performed during all pregnancies. Instead, one or more screening methods may be utilized to determine when the risk to the pregnancy warrants the risk of undergoing an invasive diagnostic procedure. The incidence of Down syndrome increases significantly with increasing maternal age. Historically, the prenatal detection of Down syndrome has focused on pregnant women at and over the age of 35, at which ages the risks of Down syndrome approach or exceed
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the risks of diagnostic procedures utilized to detect fetal Down syndrome. Therefore the standard method of prenatal screening has involved selecting women for diagnostic amniocentesis on the basis of maternal age. Age, however, is an inadequate screening criterion in that only about 20% of all Down syndrome pregnancies can be detected by carrying out amniocentesis and karyotyping on the 5% of pregnant women most at risk, that is, those aged 35 years or greater. And, because in actual clinical practice only about half of the women aged 35 years or greater undergo amniocentesis and karyotyping, fewer than 10% of Down syndrome pregnancies are prenatally detected. Web site: http://www.delphion.com/details?pn=US05252489__ •
Human gene sequence of the down syndrome critical region of human chromosome 21, coding for a serine-threonine protein kinase (MNB), expressed in the neuronal regions affected in down syndrome Inventor(s): Guimera Vilaro; Jordi (Barcelona, ES), Estivill Palleja; Xavier (Instituto de Investigacion Oncologica Autovia de Castelldefells, Km. 2, 7, Barcelona, ES), Pritchard; Melanie (Barcelona, ES) Assignee(s): Estivill Palleja; Xavier (Barcelona, ES) Patent Number: 6,251,664 Date filed: January 28, 1997 Abstract: An isolated human Down Syndrome critical region (MNB) DNA sequence having the nucleotide sequence depicted in SEQ ID NO:1; vector including the human Down Syndrome critical region (MNB) sequence; and isolated host cells containing the vector are provided. Excerpt(s): The minibrain (mnb) gene of Drosophila melanoaster encodes a serinethreonine protein kinase with an essential role in post-embryonic neurogenesis. A corresponding human gene with similar function to mnb could provide important. insights into both normal brain development and the abnormal. brain development and mental retardation observed in many congenital disorders. Trisomy 21 or Down syndrome (DS) is the most frequent human birth defect. It is associated with mental retardation and a broad spectrum of physical abnormalities. A region on human chromosome 21 has been designated the Down syndrome critical region (DSCR) and when present in three copies, this is responsible for many of the characteristic features of DS, including mental retardation. We have isolated a human homologue of mnb from the DSCR. Using a human probe of MNB, expression was detected in situ in several regions of the mouse brain, including the olfactory bulb, the cerebellum, the cerebral cortex, the pyramidal cell layer of the hippocampus and several hypothalamic nuclei. This expression pattern corresponds to the regions of the brain that are abnormal in individuals with DS and suggests that overexpression of MNB could have detrimental consequences in DS patients. Down syndrome (DS) is one of the most frequent congenital defects. There is a broad spectrum of physical abnormalities associated with the syndrome, including anomalies of the gastrointestinal tract, increased risk of leukemia, defects of the immune and endocrine systems, early onset of Alzheimer's dementia and distinct facial and physical features, but perhaps the most debilitating is a rather severe mental retardation. In most cases DS is due to three full copies of human chromosome 21 which arise primarily during maternal non-disjunction, but occasionally DS occurs in people carrying unbalanced translocations, which result in the triplication of only a part of chromosome 21. By correlating phenotype with genotype in patients with partial trisomies a region has been defined, named the DSCR (Down syndrome
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critical region) which, when present in three copies, is responsible for many of the characteristic features of DS including mental retardation (1). The phenotypic consequences of DS presumably result from the overexpression and subsequent interactions of a subset of chromosome 21 genes and the future challenge is to correlate overexpression of these genes, singly or in combination, with the presence of the DS phenotype. The first step is to identify the genes in the DSCR and then assess their potential contributions to the pathophysiology of DS. Assigning a function to a gene, particularly in humans, is not simple. Investigators rely on finding clues to function by analyzing the expression pattern of a gene, by looking for protein domains or motifs with known functions or by extrapolating from another species in which the function of the homologous gene is known. Web site: http://www.delphion.com/details?pn=US06251664__ •
Method for detecting trisomy 13 and Down syndrome by non-invasive maternal blood screening Inventor(s): Macri; James N. (170 Sidney St., Oyster Bay, NY 11771) Assignee(s): none reported Patent Number: 5,324,668 Date filed: February 3, 1993 Abstract: A method and apparatus for determining if a pregnant woman is at significant risk of carrying a fetus with Down syndrome, The method comprises measuring the pregnant woman's maternal blood levels of the free beta subunit of human chorionic gonadotropin. The level of free beta subunit of human chorionic gonadotropin individually or with other markers may be compared to reference data. A computerized apparatus for making the determination preferably using a probability density function generated from a set of reference data by a linear discriminant analysis procedure is disclosed. Excerpt(s): The present invention relates to a method for detecting fetal Down syndrome (Trisomy 21) during prenatal screening. This method also relates to other more rare but detectable chromosomal trisomies such as Trisomy 13 and Trisomy 18. More particularly the present invention relates to a method for improving detection efficiency in screening for Down syndrome by measuring the amount of the free beta subunit of human chorionic gonadotropin (hCG) in the blood of pregnant women. Down syndrome, also referred to as Trisomy 21, is the most common congenital cause of severe mental retardation. Generally, fetal Down syndrome can be determined by a diagnostic procedure including amniocentesis and karyotyping. However, this diagnostic procedure is invasive and involves risk to the woman and the fetus. Amniocentesis and karyotyping are not routinely performed during all pregnancies. Instead, one or more screening methods may be utilized to determine when the risk to the pregnancy warrants the risk of undergoing an invasive diagnostic procedure. The incidence of Down syndrome increases significantly with increasing maternal age. Historically, the prenatal search for Down syndrome has focused on pregnant women at and over the age of 35, at which ages the risks of Down syndrome approach or exceed the risks of diagnostic procedures utilized to detect fetal Down syndrome. Therefore the standard method of prenatal screening has involved selecting women for diagnostic amniocentesis on the basis of maternal age. Age, however, is an inadequate screening criterion in that only about 20% of all Down syndrome pregnancies can be detected by carrying out amniocentesis and karyotyping on the 5% of pregnant women most at risk,
244 Down Syndrome
that is, those aged 35 years or greater. And, because in actual clinical practice only about half of the women aged 35 years or greater undergo amniocentesis and karyotyping, fewer than 10% of Down syndrome pregnancies are prenatally detected. Web site: http://www.delphion.com/details?pn=US05324668__ •
Method for determining the risk of trisomy 21 in the second trimester Inventor(s): Vintzileos; Anthony M. (Bridgewater, NJ), Egan; James F.X. (Longmeadow, MA) Assignee(s): University Of Medicine & Dentistry of NJ (Newark, NJ) Patent Number: 5,622,176 Date filed: July 26, 1995 Abstract: The present invention pertains to a method for the prenatal detection of trisomy 21 in the second trimester by adjusting the risk of trisomy 21 based on fetal long bone biometry which comprises the steps of (a) measuring ultrasonically the biparietal diameter and the length of the femur, humerus, tibia, and fibula bones in fetuses of a patient population in the second trimester; (b) performing amniocentesis on the patient population in step (a) to determine which fetuses are normal and which fetuses have trisomy 21; (c) from the normal fetuses, deriving equations describing the predicted lengths of the lemur, humerus, tibia, and fibula based on the biparietal diameter measurements; (d) calculating a ratio of observed lengths to predicted lengths of the femur, humerus, tibia, and fibula for all fetuses; (e) comparing the ratios calculated in step (d) for normal fetuses against the ratios calculated for fetuses having trisomy 21 and determining a threshold, as a percentile of these ratios, for abnormally short bone lengths in the fetuses having trisomy 21; and (f) employing the threshold determined in step (e) to detect prenatally trisomy 21 by fetal long bone biometry. In another embodiment, the method comprises the steps of (f) employing the threshold determined in step (e) to determine sensitivity and specificity in detecting prenatally trisomy 21 by fetal long bone biometry; and (g) employing the sensitivity and specificity determined in step (f) to adjust the risk of trisomy 21. Excerpt(s): This invention relates to a method for the prenatal detection of trisomy 21 in the second trimester by adjusting the risk of trisomy 21 based on fetal long bone biometry. More particularly, this invention relates to (a) measuring ultrasonically the biparietal diameter and the length of the femur, humerus, tibia, and fibula bones in fetuses of a patient population in the second trimester; (b) performing amniocentesis on the patient population in step (a) to determine which fetuses are normal and which fetuses have trisomy 21; (c) from the normal fetuses, deriving equations describing the predicted lengths of the femur, humerus, tibia, and fibula based on the biparietal diameter measurements; (d) calculating a ratio of observed lengths to predicted lengths of The femur, humerus, tibia, and fibula for all fetuses; (e) comparing the ratios calculated in step (d) for normal fetuses against the ratios calculated for fetuses having trisomy 21 and determining a threshold, as a percentile of these ratios, for abnormally short bone lengths in the fetuses having trisomy 21; and (f) employing the threshold determined in step (e) to detect prenatally trisomy 21 by fetal long bone biometry. In another embodiment, the method comprises the steps of (f) employing the threshold determined in step (e) to determine sensitivity and specificity in detecting prenatally trisomy 21 by fetal long bone biometry; and (g) employing the sensitivity and specificity determined in step (f) to adjust the risk of trisomy 21. The disclosures referred to herein to illustrate the background of the invention and to provide additional detail with
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respect to its practice are incorporated herein by reference. For convenience, the disclosures are referenced in the following text and respectively grouped in the appended bibliography. Trisomy 21 (trisomy G, Down's syndrome, mongolism) is a condition characterized by a small, anteroposteriorly flattened skull, short, flat-bridged nose, epicanthal fold, short phalanges, and widened space between the first and second digits of hands and feet, with moderate to severe retardation, and associated with a chromosomal abnormality. In about 85% of cases of trisomy 21, there is an extra chromosome 21. Typically, the affected children are born to older mothers, but sporadic or trisomic mongolism may also occur in children of young mothers. The overall incidence of trisomy 21 is about 1:700 live births, but there is a marked variability depending on maternal age. In the early child-bearing years, the incidence of trisomy 21 is about 1:2000 live births whereas for mothers over 40, the incidence rises to about 45:1000 live births. Close to 50% of infants with trisomy 21 are born to mothers over 35. Nevertheless, recent studies have shown that the extra chromosome 21 can occasionally come from the father. Web site: http://www.delphion.com/details?pn=US05622176__ •
Methods of treatment of down syndrome by interferon antagonists Inventor(s): Maroun; Leonard E. (Springfield, IL) Assignee(s): Meiogen Biotechnology Corporation (Springfield, IL) Patent Number: 5,780,027 Date filed: July 14, 1995 Abstract: The present invention relates to a process for ameliorating or preventing neurological diseases that are caused, in part, by an increased and/or abnormal responsivity to interferon. Down Syndrome (DS) and Alzheimer's Disease (AD) are examples of such diseases. Specifically, the invention provides a method for treating subjects suffering from or at risk for such diseases by the administration of a pharmacological preparation that antagonizes interferon's action. Excerpt(s): The present invention relates to a process for ameliorating or preventing neurological diseases that are caused, in part, by an increased and/or abnormal responsivity to interferon. Down Syndrome (DS) and Alzheimer's Disease (AD) are examples of such diseases. Specifically, the invention provides a method for treating subjects suffering from or at risk for such diseases by the administration of a pharmacological preparation that antagonizes interferons' action. Interferons are proteins that alter and regulate the transcription of genes within a cell by binding to interferon receptors on the regulated cell's surface and thus prevent viral replication within the cells. There are five types of interferons (IFN), which are designated.alpha. (formerly.alpha.sub.1),.omega. (formerly.alpha.sub.2),.beta.,.gamma. and.tau. Mature human interferons are between 165 and 172 amino acids in length. In humans IFN.alpha. and IFN-.omega. are encoded by multiple, closely related non-allelic genes. Additionally, there are pseudo-genes of IFN-.alpha. and IFN-.omega. By contrast, IFN.beta. and IFN-.gamma. are encoded by unique genes. The interferons can be grouped into two types. IFN-.gamma. is the sole type II interferon; all others are type I interferons. Type I and type II interferons differ in gene structure (type II interferon genes have three exons, type I one), chromosome location (in humans, type II is located on chromosome-12; the type I interferon genes are linked and on chromosome-9), and the types of tissues where they are produced (type I interferons are synthesized ubiquitously, type II by lymphocytes). Type I interferons competitively inhibit each
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others binding to cellular receptors, while type II interferon has a distinct receptor. Reviewed by Sen, G. C. & Lengyel, P., 1992, J. Biol. Chem. 267:5017-5020. Web site: http://www.delphion.com/details?pn=US05780027__ •
Prenatal down syndrome screening with assays specific for UGP Inventor(s): Walker; Roger P. (Benicia, CA), Cuckle; Howard S. (North Yorkshire, GB) Assignee(s): Chiron Diagnostics Corporation (Medfield, MA) Patent Number: 5,716,853 Date filed: April 30, 1996 Abstract: Herein disclosed are methods for prenatally assessing risks of a pregnancy being affected by Down syndrome by testing maternal urine samples for levels of urinary gonadotropin peptide (UGP) elevated above normal. The methods employ immunoassays that are highly specific for UGP and have molar cross-reactivities of less than about 10% with intact hCG, with.beta.-subunit hCG, and with.alpha.-subunit hCG. The immunoassay methods of this invention are useful to test first trimester maternal urine samples. Among other benefits, first trimester prenatal screening provides the opportunity to terminate the pregnancy at an early gestational age, in the case of an unfavorable outcome. Excerpt(s): The present invention is in the field of prenatal diagnosis. It concerns noninvasive methods to screen prenatally for fetal Down syndrome by immunoassays employing antibodies that are specific for urinary gonadotropin peptide (UGP) ›also known as.beta.-core or urinary gonadotropin fragment (UGF)!. Trisomy 21, commonly known as Down syndrome, is characterized by an extra copy of chromosome 21. People afflicted with Down syndrome have severe mental retardation, reduced life expectancies, and abnormal immune responses that predispose them to serious infections as well as thyroid autoimmunity. Further, 40% of Down syndrome patients have congenital heart disease and a 10 to 20-fold increased risk of developing leukemia over the general population. All Down syndrome patients older than 40 develop neuropathological changes characteristic of Alzheimer's disease. Prenatal tests to detect aneuploidy, such as trisomy 21, by amniocentesis or chorionic villus sampling (CVS) have been available since the late 1960s. Amniocentesis is the most common invasive prenatal diagnostic procedure. In amniocentesis, amniotic fluid is sampled by inserting a hollow needle through the mother's anterior abdominal and uterine walls into the amniotic cavity by piercing the chorion and amnion. It is usually performed in the second trimester of pregnancy. CVS is performed primarily during the first trimester, and involves collecting cells from the chorion which develops into the placenta. Web site: http://www.delphion.com/details?pn=US05716853__
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•
Screening extra-cellular body fluids for superoxide dismutase (SOD-1) for determining fetal trisomy 21 down syndrome Inventor(s): Khan; Abbas A. (Houston, TX), Merril; Carl R. (Rockville, MD), Warrington; Richard E. (Houston, TX) Assignee(s): Monoclonetics International, Inc. (Houston, TX) Patent Number: 4,940,659 Date filed: February 20, 1987 Abstract: Disclosed is a screening assay for determining the amount of Superoxide Dismutase (SOD-1) in extra-cellular body fluids, for use in determining Trisomy 21 Down syndrome in a fetus. The assay can be done by any of a number of well known techniques including Radioimmunoassay, an Enzyme Linked Immunoassay, or a luminescence assay, single or tandem antibody type, carried out in solid or liquid phase. Polyclonal or monoclonal antibodies can be used. In the preferred embodiment, the assay is used to determine SOD-1 levels in amniotic fluid. A level above a threshold indicates a high probability of Trisomy 21 Down Syndrome for the fetus. Excerpt(s): The invention relates to the detection of potential Down syndrome progeny (Trisomy 21) by screening for the presence of SOD-1 in extra-cellular body fluid. Trisomy 21 (i.e., one additional 21st chromosome) accounts for 95 per cent of all cases of Down syndrome. This condition is among the most common genetic defects, occurring in about 1 in every 800 births. Patients with this syndrome have characteristic faces, are mentally retarded, and at least 30 per cent have congenital heart disease. Trisomy 21 occurs when homologous chromosomes fail to separate at anaphase, resulting in nondisjunction and the production of one monosomic and one trisomic daughter nuclei. In chromosomally normal women, the frequency of nondisjunction is age related. For women ages 20 to 30, the incidence increases linearly from about 0.3 per 1000 births to about 2 per 1000 births. After the age of 30, the incidence increases exponentially, at a rate of about 30 per cent per year. Women over 35 give birth to 35 per cent of all children with Trisomy 21 Down Syndrome. Web site: http://www.delphion.com/details?pn=US04940659__
•
Urinary screening for down syndrome and other aneuploidies Inventor(s): Iles; Raymond K. (West Drayton, GB), Cuckle; Howard S. (Harrogate, GB), Chard; Timothy (London, GB) Assignee(s): Yale University (New Haven, CT) Patent Number: 6,025,149 Date filed: July 3, 1996 Abstract: This invention represents a significant advance in prenatal diagnosis by providing urinary screening to detect fetal aneuploidies. Herein disclosed are methods for prenatally assessing risks of a pregnancy being affected by Down syndrome and other aneuploidies by testing maternal urine samples for levels of.beta.-core-hCG. Levels of maternal urinary.beta.-core-hCG above normal indicate a risk that the pregnancy is affected with Down syndrome, and in general risks of other fetal aneuploidies are indicated by either lower than normal or higher than normal maternal urinary.beta.-core-hCG levels. Assessments can be made based on urinary.beta.-core-
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hCG levels alone or in conjunction with levels of other urinary and/or serum markers, ultrasound parameters and other factors, such as, maternal age. Excerpt(s): The present invention is in the field of prenatal diagnosis. It concerns noninvasive methods to screen prenatally for fetal Down syndrome and other fetal aneuploidies by determining the levels of urinary.beta.-core-hCG [also known as urinary gonadotropin peptide (UGP),.beta.-core,.beta.-core fragment, or urinary gonadotropin fragment (UGF)] in maternal urine samples, alone or in conjunction with other markers. Prenatal tests to detect fetal aneuploidies, such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), triploidy (69 chromosomes), Klinefelter syndrome (47, XXY), triple X (47,XXX) and Turner syndrome (45,X) among other aneuploidies, by amniocentesis or chorionic villus sampling (CVS) have been available since the late 1960s. Amniocentesis is the most common invasive prenatal diagnostic procedure. In amniocentesis, amniotic fluid is sampled by inserting a hollow needle through the mother's anterior abdominal and uterine walls into the amniotic cavity by piercing the chorion and amnion. It is usually performed in the second trimester of pregnancy. CVS is performed primarily during the first trimester, and involves collecting cells from the chorion which develops into the placenta. Another invasive prenatal diagnostic technique is cordocentesis or percutaneous umbilical cord blood sampling, commonly known as fetal blood sampling. Fetal blood sampling involves obtaining fetal blood cells from vessels of the umbilical cord, and is often performed about the 20th gestational week. Web site: http://www.delphion.com/details?pn=US06025149__
Patent Applications on Down Syndrome 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 Down syndrome: •
Down syndrome critical region 1-like protein Inventor(s): Streeter, David G. (Boulder Creek, CA), Tingley, Debora W. (San Francisco, CA), Edwards, Carla M. (Half Moon Bay, CA), Loring, Jeanne F. (Foster City, CA) Correspondence: INCYTE CORPORATION (formerly known as Incyte; Genomics, Inc.); 3160 PORTER DRIVE; PALO ALTO; CA; 94304; US Patent Application Number: 20030186333 Date filed: November 6, 2002 Abstract: The invention provides a Down syndrome critical region 1-like 1 protein, its encoding cDNAs, and antibodies that specifically bind the protein. The invention also provides for the use of these compositions in the diagnosis, prognosis, treatment and evaluation of progression and treatment of neurodegenerative disorders. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 09/614,474 filed Jul. 11, 2000. This invention relates to Down syndrome critical region 1-like 1 protein, its encoding cDNA, and an antibody that specifically bind the protein and their use in the diagnosis, prognosis, treatment and evaluation of the progression and treatment of
10
This has been a common practice outside the United States prior to December 2000.
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neurodegenerative disorders, and in particular, Alzheimer's disease. Alzheimer's disease is a progressive neurodegenerative disorder that is characterized by the formation of senile plaques and neurofibrillary tangles containing amyloid beta peptide. These plaques are found in limbic and association cortices of the brain, including hippocampus, temporal cortices, cingulate cortex, amygdala, nucleus basalis and locus caeruleus. Early in Alzheimer's pathology, physiological changes are visible in the cingulate cortex (Minoshima et al. (1997) Annals of Neurology 42:85-94). In subjects with advanced Alzheimer's disease, accumulating plaques damage the neuronal architecture in limbic areas and eventually cripple the memory process. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Methods for inhibiting cognitive deterioration in adults with down's syndrome Inventor(s): Belanoff, Joseph K. (Woodside, CA) Correspondence: TOWNSEND AND TOWNSEND AND CREW, LLP; TWO EMBARCADERO CENTER; EIGHTH FLOOR; SAN FRANCISCO; CA; 94111-3834; US Patent Application Number: 20030064974 Date filed: August 28, 2002 Abstract: This invention generally pertains to the field of psychiatry. In particular, this invention pertains to the discovery that agents capable of inhibiting the binding of cortisol to its receptors can be used in methods for preventing or reversing cognitive deterioration in adults with Down's syndrome. Mifepristone, a potent specific glucocorticoid receptor antagonist, can be used in these methods. The invention also provides a kit for preventing or reversing cognitive deterioration in a DS patient including a glucocorticoid receptor antagonist and instructional material teaching the indications, dosage and schedule of administration of the glucocorticoid receptor antagonist. Excerpt(s): The present application claims priority to U.S. Ser. No. 60/316,653 filed Aug. 31, 2001 herein incorporated by reference in its entirety. This invention relates to the discovery that agents capable of inhibiting the biological action of the glucocorticoid receptor can be used in methods for preventing, reversing, or inhibiting cognitive deterioration in adults with Down's syndrome. Down's syndrome (DS) is the most common genetic cause of mental retardation and probably the earliest identified condition associated with mental retardation (Pulsifer, J Int Neuropsychol Soc 2:159-76 (1996). DS arises from one of three chromosomal abnormalities. Most commonly (95% of cases) DS is the result of trisomy 21, or the presence of an extra chromosome 21 in otherwise diploid cells. Trisomy 21 usually results from nondisjunction of chromosome 21 during meiosis of the gametes, and brings the total number of chromosomes in the adult offspring to 47. DS may also result (in about 2-4% of cases) from translocation events, occurring when a fragment of chromosome 21 becomes attached to another chromosome, most typically chromosome 14. The rarest form of DS(about 1-4% of cases) results from nondisjunction of chromosome 21 during early embryogenesis. Such individuals are mosaic, with both normal and trisomic cells being present. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Trisomy 21 cytotrophoblast cultures,and uses thereof for obtaining trisomy 21 markers Inventor(s): Frendo, Jean-Louis; (Paris, FR), Evain-Brion, Daniele; (Bourg-La-Reine, FR) Correspondence: MORGAN LEWIS & BOCKIUS LLP; 1111 PENNSYLVANIA AVENUE NW; WASHINGTON; DC; 20004; US Patent Application Number: 20030138435 Date filed: December 16, 2002 Abstract: The invention concerns trisomy 21 cytotrophoblast cultures. Proteins differentially secreted by said cultures and by normal cytotrophoblast cultures are in particular useful as trisomy 21 markers. Excerpt(s): The invention relates to trisomy 21 cytotrophoblasts cultures, and to uses thereof. Trisomy 21, responsible for Down's syndrome which is more commonly called mongolism, is the most frequent of autosomal trisomies since observed in nearly 1 out of 800 neonates during childbirth [FERGUSON-SMITH et al., Prenat. Diagn., 4, 5-44, (1984)]. It is the major genetic cause of mental retardation [CUNNINGHAM et al., Williams Obstetrics, ed. 19, 919-938, (1993)]. Prenatal diagnosis of trisomy 21 is essentially based on the establishment of the fetal karyotype, an examination most often performed on fetal cells of the amniotic fluid collected by amniocentesis, more rarely on trophoblast cells collected by biopsy of the chorionic villi. 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 Down syndrome, 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 “Down syndrome” (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 Down syndrome. You can also use this procedure to view pending patent applications concerning Down syndrome. 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. BOOKS ON DOWN SYNDROME Overview This chapter provides bibliographic book references relating to Down syndrome. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Down syndrome 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 “Down syndrome” (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 Down syndrome: •
Alzheimer Disease, Down Syndrome, and Their Relationship Source: New York, NY: Oxford University Press. 1993. 297 p. Contact: Available from Oxford University Press. 200 Madison Avenue, New York, NY 10016. (800) 451-7556. PRICE: $85.00. ISBN: 0192623826. Summary: This book considers the association between Down syndrome (DS) and Alzheimer's disease (AD). It provides overviews of each disorder, followed by detailed accounts and analyses of hypotheses that attempt to account for the presence of DS as a risk factor for AD. Specific discussions include clinical and neurological observations of the association between AD and DS, diagnostic and management considerations of AD in people with DS, assessment of cognitive functioning in people with DS who develop AD, communication impairments, neuroimaging in adults with DS, biological markers for AD in the general population and in DS, and the etiological aspects.
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•
Improving the Communication of People with Down Syndrome Source: Baltimore, MD: Paul H. Brookes Publishing Company. 1999. 289 p. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775. Fax (410) 337-8539. E-mail:
[email protected]. Website: www.brookespublishing.com. PRICE: $34.95 plus shipping and handling. ISBN: 1557663505. Summary: This book provides a framework for assessing and treating speech, language, and communication problems in children and adults with Down syndrome. The authors describe the speech, language, and communication abilities of people with Down syndrome; review the assessments and interventions that have proved effective in promoting the development of communication skills; and summarize long-term family outcomes. Topics include the biological bases of speech; the evaluation of communication skills; language development in children and adolescents; fluency, intelligibility, and communicative effectiveness; interventions to improve communication skills; speech and language skill enhancement for adults; and assistive technology. The authors focus on individuals specific abilities, the relationships among their specific cognitive and language skills, and how these abilities contribute to the communication development process from childhood to adulthood. Appendices include lists of resources and World Wide Web sites devoted to Down syndrome and related topics. Each of the twelve chapters includes references, and a subject index concludes the volume.
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Communication Skills in Children With Down Syndrome: A Guide for Parents Source: Rockville, MD: Woodbine House, Inc. 1994. 250 p. Contact: Available from Woodbine House, Inc. 5615 Fishers Lane, Rockville, MD 20852. (800) 843-7323. PRICE: $14.94 plus shipping and handling. ISBN: 0933149530. Summary: This book provides parents with information about speech and language development in children with Down syndrome. The book describes what to expect as communication skills progress from infancy through early adolescence, how Down syndrome can affect those skills, and what parents can do to help maximize their child's potential in this crucial area of development. The book includes hundreds of activities and exercises for parents to do at home with their children that address specific language and speech problems. The author also discusses speech and language assessment and therapy, hearing problems, school performance, and speech intelligibility. A subject index concludes the book.
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Keys to parenting a child with Down Syndrome Source: Hauppauge, NY: Barron's Educational Series. 1993. 200 pp. Contact: Available from Barron's Educational Series, 250 Wireless Boulevard, Hauppauge, NY 11788. Telephone: (800) 645-3476. $5.95 plus $1.75 postage and handling. Summary: This book is designed to provide parents of a Down Syndrome child information about the current medical perspective on the syndrome, and addresses various aspects of parenting a child with Down Syndrome. Topics covered include myths and facts about Down Syndrome, adjusting to a child with Down Syndrome, balancing family relationships, respite care, health problems, early development, tips for managing behavior and discipline, recent legislation on children with disabilities,
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mainstreaming, assistive technology, sex education, and alternatives for housing, employment, and financial planning for the grown Down Syndrome child. •
Differences in common: Straight talk on mental retardation, Down syndrome, and life Source: Bethesda, MD: Woodbine House. 1991. 231 pp. Contact: Available from Woodbine House, 6510 Bells Mill Road, Bethesda, MD 20817. Telephone: (800) 843-7323 or (301) 897-3570 / fax: (301) 897- 5838. $14.95. Summary: This book contains essays based upon the author's interactions with her son who has Down syndrome, which is a clinical cause of mental retardation. It covers his life from birth to young adulthood, and it relates the story of a family learning to accommodate a person with special health needs and their efforts to provide appropriate parenting.
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Down syndrome: The facts Source: New York, NY: Oxford University Press. 1990. 205 pp. Contact: Available from Oxford University Press, 2001 Evans Road, Cary, NC 27513. Telephone: (800) 451-7556 or (919) 677-0977 / fax: (919) 677- 1303. $18.95. Summary: This book is written for parents who have a child with Down syndrome. It covers the challenges parent face during infancy, childhood and adulthood, causes of Down syndrome, antenatal diagnosis, development, health and education. It also gives advice on behavior management and coping with the reactions of family members and friends. Types of services and some controversial treatments are discussed.
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A parent's guide to Down syndrome: Toward a brighter future Source: Baltimore, MD: Paul H. Brookes Publishing Company. 1990. 315 pp. Contact: Available from Paul H. Brookes Publishing Company, P.O. Box 10624, Baltimore, MD 21285-0624. Telephone: (800) 638-3775 or (410) 337-9580 / fax: (410) 3378539 / e-mail:
[email protected]. $20.00. Summary: This book, a new edition of 'Down Syndrome: Growing and Learning,' focuses on the progress that has been made to create better life chances for these children. It provides guidance for parents and others working with children with Down syndrome to help them further the physical, social, mental, and emotional development of the children, with special emphasis given to early intervention. New areas covered include educational programming, language development, and the sexual development of the adolescent.
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 “Down syndrome” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “Down syndrome” (or a synonym) in
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their titles. The following is indicative of the results you might find when searching for “Down syndrome” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
A Parent's Guide to Down Syndrome : Toward a Brighter Future, Revised Edition by Siegfried M. Pueschel (Editor); ISBN: 1557664528; http://www.amazon.com/exec/obidos/ASIN/1557664528/icongroupinterna
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Adolescents With Down Syndrome: Toward a More Fulfilling Life by Siegfried M. Pueschel (Editor), Maria Sustrova (Editor) (1997); ISBN: 1557662819; http://www.amazon.com/exec/obidos/ASIN/1557662819/icongroupinterna
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Advances in Down Syndrome by Valentine Dmitriev, Patricia L. Oelwein (Editor); ISBN: 0875620922; http://www.amazon.com/exec/obidos/ASIN/0875620922/icongroupinterna
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Alzheimer Disease, Down Syndrome, and Their Relationship (Oxford Medical Publications) by J. M. Berg (Editor), et al; ISBN: 0192623826; http://www.amazon.com/exec/obidos/ASIN/0192623826/icongroupinterna
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Babies With Down Syndrome: A New Parent's Guide (The Special-Needs Collection) by Karen Stray-Gundersen (Editor) (1995); ISBN: 0933149646; http://www.amazon.com/exec/obidos/ASIN/0933149646/icongroupinterna
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Biomedical Concerns in Persons With Down Syndrome by Siegfried M. Pueschel (Editor), Jeanette K. Pueschel (Editor); ISBN: 1557660891; http://www.amazon.com/exec/obidos/ASIN/1557660891/icongroupinterna
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Chris Burke: He Overcame Down Syndrome (Reaching Your Goal) by Gregory Lee, Glenn Davis (Illustrator); ISBN: 0865932638; http://www.amazon.com/exec/obidos/ASIN/0865932638/icongroupinterna
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Classroom Language Skills for Children With Down Syndrome: A Guide for Parents and Teachers (Topics in Down Syndrome) by Libby, Ph.D Kumin (2001); ISBN: 1890627119; http://www.amazon.com/exec/obidos/ASIN/1890627119/icongroupinterna
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Clinical Perspectives in the Management of Down Syndrome (Disorders of Human Learning, Behavior, and Communication) by Don C. Van Dyke, et al; ISBN: 038796987X; http://www.amazon.com/exec/obidos/ASIN/038796987X/icongroupinterna
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Common Threads: Celebrating Life with Down Syndrome by Cynthia Kidder, Brian Skotko (2001); ISBN: 1930868049; http://www.amazon.com/exec/obidos/ASIN/1930868049/icongroupinterna
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Communication Behaviors and Skills of Children Having Down Syndrome (Journal of Childhood Communication Disorder, Special Issue); ISBN: 9999641008; http://www.amazon.com/exec/obidos/ASIN/9999641008/icongroupinterna
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Communication Skills in Children With Down Syndrome: A Guide for Parents (Topics in Down Syndrome) by Libby, PH.D. Kumin; ISBN: 0933149530; http://www.amazon.com/exec/obidos/ASIN/0933149530/icongroupinterna
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Continuity and Change in the Social Competence of Children With Autism, Down Syndrome, and Developmental Delays (Monographs of the Society for Research) by Marian Sigman, et al (1999); ISBN: 0631215913; http://www.amazon.com/exec/obidos/ASIN/0631215913/icongroupinterna
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Count Us In: Growing Up with Down Syndrome by Jason Kingsley (Author), Mitchell Levitz (Author) (1994); ISBN: 015622660X; http://www.amazon.com/exec/obidos/ASIN/015622660X/icongroupinterna
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Danny: The Murder of a Man With Down Syndrome by Patricia Smith, George Smith (2000); ISBN: 0595005136; http://www.amazon.com/exec/obidos/ASIN/0595005136/icongroupinterna
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Differences in Common: Straight Talk on Mental Retardation, Down Syndrome, and Your Life by Marilyn Trainer, Helen Featherstone (2003); ISBN: 0933149409; http://www.amazon.com/exec/obidos/ASIN/0933149409/icongroupinterna
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Don't Sing Any Sad Songs: A Down Syndrome Daughter's Joyful Journey by Rosalie B. Icenhower, Rosalie Icenhower; ISBN: 1893162834; http://www.amazon.com/exec/obidos/ASIN/1893162834/icongroupinterna
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Down Is Up for Aaron Eagle: A Mother's Spiritual Journey With Down Syndrome by Vicki Noble, Vicki Nobel; ISBN: 0062507370; http://www.amazon.com/exec/obidos/ASIN/0062507370/icongroupinterna
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Down Syndrome by Ann Garcia; ISBN: 096301580X; http://www.amazon.com/exec/obidos/ASIN/096301580X/icongroupinterna
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Down Syndrome (Diseases and Disorders) by Christina M. Girod (2001); ISBN: 1560068248; http://www.amazon.com/exec/obidos/ASIN/1560068248/icongroupinterna
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Down Syndrome (Venture Book (Franklin Watts, Inc.).) by Salvatore Tocci (2000); ISBN: 0531115895; http://www.amazon.com/exec/obidos/ASIN/0531115895/icongroupinterna
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Down Syndrome : Visions for the 21st Century by William I. Cohen (Editor), et al; ISBN: 0471418153; http://www.amazon.com/exec/obidos/ASIN/0471418153/icongroupinterna
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Down Syndrome Across the Life Span by Monica Cuskelly (Editor), et al; ISBN: 1861562306; http://www.amazon.com/exec/obidos/ASIN/1861562306/icongroupinterna
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Down Syndrome and Alzheimer Disease by National Down Syndrome Society Conference on Down Syndrome and Alzheim, et al; ISBN: 0471588415; http://www.amazon.com/exec/obidos/ASIN/0471588415/icongroupinterna
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Down Syndrome and Health Care by Vee Prasher, Beryl Smith; ISBN: 1902519205; http://www.amazon.com/exec/obidos/ASIN/1902519205/icongroupinterna
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Down Syndrome Behind the Dykes: Research in the Netherlands by Erik A. B. De Graaf (Editor), et al (1998); ISBN: 9053836101; http://www.amazon.com/exec/obidos/ASIN/9053836101/icongroupinterna
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Down Syndrome, One Family's Journey: Beth Exceeds Expectations by Donald Bakely, Bakely Donald; ISBN: 1571290907; http://www.amazon.com/exec/obidos/ASIN/1571290907/icongroupinterna
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Down Syndrome: A Promising Future, Together by Terry J. Hassold (Editor), David Patterson (Editor); ISBN: 0471296872; http://www.amazon.com/exec/obidos/ASIN/0471296872/icongroupinterna
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Down Syndrome: A Resource Handbook by Carol Tingey (Editor); ISBN: 0890793115; http://www.amazon.com/exec/obidos/ASIN/0890793115/icongroupinterna
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Down Syndrome: A Review of Current Knowledge by J. A. Rondal (Editor), et al (1999); ISBN: 1861560621; http://www.amazon.com/exec/obidos/ASIN/1861560621/icongroupinterna
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Down Syndrome: Advances in Biomedicine and the Behavioral Science S by S. M. Pueschel (Editor); ISBN: 0938552503; http://www.amazon.com/exec/obidos/ASIN/0938552503/icongroupinterna
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Down Syndrome: Advances in Medical Care by Ira Lott, Ernest E. McCoy; ISBN: 0471561843; http://www.amazon.com/exec/obidos/ASIN/0471561843/icongroupinterna
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Down Syndrome: Growing and Learning (Human Potentials for Children Series) by S. M. Pueschel (Editor), F. R. Seigfried; ISBN: 0836228057; http://www.amazon.com/exec/obidos/ASIN/0836228057/icongroupinterna
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Down Syndrome: Living and Learning in the Community by Lynn Nadel (Editor), Donna Rosenthal (Editor); ISBN: 0471022012; http://www.amazon.com/exec/obidos/ASIN/0471022012/icongroupinterna
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Down Syndrome: Moving Through Life by Yvonne R. Burns (Editor), Pat Gunn (Editor) (1993); ISBN: 0412461803; http://www.amazon.com/exec/obidos/ASIN/0412461803/icongroupinterna
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Down Syndrome: New Perspective in Biomedicine and the Behavioral Sciences by Siegfried M. and Rynders, John E. Pueschel; ISBN: 0824071980; http://www.amazon.com/exec/obidos/ASIN/0824071980/icongroupinterna
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Down Syndrome: Now What Do I Do by Anne F. Squires, et al (1990); ISBN: 0962639303; http://www.amazon.com/exec/obidos/ASIN/0962639303/icongroupinterna
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Down Syndrome: Successful Parenting of Children With Down Syndrome by John F. Unruh (1994); ISBN: 0961533242; http://www.amazon.com/exec/obidos/ASIN/0961533242/icongroupinterna
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Down Syndrome: the Facts by Mark Selikowitz; ISBN: 0192626620; http://www.amazon.com/exec/obidos/ASIN/0192626620/icongroupinterna
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Early Communication Skills for Children With Down Syndrome: A Guide for Parents and Professionals by Libby Kumin (2003); ISBN: 1890627275; http://www.amazon.com/exec/obidos/ASIN/1890627275/icongroupinterna
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Early Education for Children With Down Syndrome: Time to Begin by Valentine Dmitriev (2001); ISBN: 0890798605; http://www.amazon.com/exec/obidos/ASIN/0890798605/icongroupinterna
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Etiology and Pathogenesis of Down Syndrome by Charles J. Epstein (Editor), et al; ISBN: 047112317X; http://www.amazon.com/exec/obidos/ASIN/047112317X/icongroupinterna
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Everything You Need to Know About Down Syndrome (Need to Know Library) by Mary Bowman-Kruhm; ISBN: 0823929493; http://www.amazon.com/exec/obidos/ASIN/0823929493/icongroupinterna
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Exceptional Language Development in Down Syndrome : Implications for the Cognition-Language Relationship by Jean A. Rondal (Author) (1994); ISBN: 0521361672; http://www.amazon.com/exec/obidos/ASIN/0521361672/icongroupinterna
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Fine Motor Skills in Children With Down Syndrome: A Guide for Parents and Professionals (Topics in Down Syndrome) by Maryanne Bruni (1998); ISBN: 1890627038; http://www.amazon.com/exec/obidos/ASIN/1890627038/icongroupinterna
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For the Love of Matthew: Growing Up With Down Syndrome by Janice Credit Houska (2002); ISBN: 1553951719; http://www.amazon.com/exec/obidos/ASIN/1553951719/icongroupinterna
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Genetic Disorders Sourcebook: Basic Consumer Health Information About Hereditary Diseases and Disorders, Including Cystic Fibrosis, Down Syndrome, Hemophilia, Huntington's Disease (Health Reference Series) by Kathy Massimini (Editor) (2000); ISBN: 0780802411; http://www.amazon.com/exec/obidos/ASIN/0780802411/icongroupinterna
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Gross Motor Skills in Children With Down Syndrome: A Guide for Parents and Professionals (Topics in Down Syndrome) by Patricia C. Winders (1997); ISBN: 0933149816; http://www.amazon.com/exec/obidos/ASIN/0933149816/icongroupinterna
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Heart Disease in Persons With Down Syndrome by Bruno, MD Marino (Editor), Siegfried M. Pueschel (Editor); ISBN: 155766224X; http://www.amazon.com/exec/obidos/ASIN/155766224X/icongroupinterna
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Improving the Communication of People With Down Syndrome by Jon F. Miller (Editor), et al (1998); ISBN: 1557663505; http://www.amazon.com/exec/obidos/ASIN/1557663505/icongroupinterna
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International Conference on Chromosome 21 & Medical Research on Down Syndrome: March, Barcelona, 1997: Abstracts (Cytogenetics & Cell Genetics) by M. Trueta (Editor), Agusti Seres-Santamaria (Editor) (1997); ISBN: 3805565321; http://www.amazon.com/exec/obidos/ASIN/3805565321/icongroupinterna
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Jackie: The Heart Warming, Inspirational True Story of a Remarkable Down Syndrome Girl by Dan Junot, et al; ISBN: 0971724601; http://www.amazon.com/exec/obidos/ASIN/0971724601/icongroupinterna
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Karina Has Down Syndrome: One Family's Account of the Early Years With a Child Who Has Special Needs by Cheryl Rogers, et al (1999); ISBN: 1853028207; http://www.amazon.com/exec/obidos/ASIN/1853028207/icongroupinterna
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Let's Talk About Down Syndrome (Let's Talk Library) by Melanie Apel Gordon; ISBN: 0823951979; http://www.amazon.com/exec/obidos/ASIN/0823951979/icongroupinterna
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Living With Down Syndrome by Jenny Bryan (1999); ISBN: 081725577X; http://www.amazon.com/exec/obidos/ASIN/081725577X/icongroupinterna
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Medical & Surgical Care for Children With Down Syndrome: A Guide for Parents (Topics in Down Syndrome) by Don C., Md. Van Dyke (Editor), et al (1995); ISBN: 0933149549; http://www.amazon.com/exec/obidos/ASIN/0933149549/icongroupinterna
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Medical Care in Down Syndrome: A Preventive Medicine Approach (Pediatric Habilitation, Vol 8) by Paul T. Rogers, et al; ISBN: 082478684X; http://www.amazon.com/exec/obidos/ASIN/082478684X/icongroupinterna
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Molecular Genetics of Chromosome 21 and Down Syndrome: Proceedings (Progress in Clinical and Biological Research, Vol. 360) by David Patterson (Editor), et al; ISBN:
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0471568384; http://www.amazon.com/exec/obidos/ASIN/0471568384/icongroupinterna •
Molecular structure of the number 21 chromosome and Down syndrome; ISBN: 0897662954; http://www.amazon.com/exec/obidos/ASIN/0897662954/icongroupinterna
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Molecular Structure of the Number 21 Chromosome and Down Syndrome (Annals of the New York Academy of Sciences, Vol 450) by George F. Smith (Editor), N.Y.) National Down Syndrome Society Symposium 1984 New York; ISBN: 0897662946; http://www.amazon.com/exec/obidos/ASIN/0897662946/icongroupinterna
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New Approaches to Down Syndrome by Brian Stratford (Editor), Pat Gunn (Editor) (1996); ISBN: 0304333506; http://www.amazon.com/exec/obidos/ASIN/0304333506/icongroupinterna
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New Perspectives on Down Syndrome by Siegfried M. Pueschel (Contributor), et al; ISBN: 0933716699; http://www.amazon.com/exec/obidos/ASIN/0933716699/icongroupinterna
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Oncology and Immunology of Down Syndrome (Progress in Clinical and Biological Research, Vol 246) by Ernest E. McCoy (Editor), Charles J. Epstein (Editor); ISBN: 0471638110; http://www.amazon.com/exec/obidos/ASIN/0471638110/icongroupinterna
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Oncology and immunology of Down Syndrome : proceedings of the National Down Syndrome Society Symposium held in New York, December 4 and 5, 1986; ISBN: 0845150960; http://www.amazon.com/exec/obidos/ASIN/0845150960/icongroupinterna
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Overview of Down Syndrome by Siegfried Pueschel; ISBN: 9998115426; http://www.amazon.com/exec/obidos/ASIN/9998115426/icongroupinterna
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Perceptual-Motor Behavior in Down Syndrome by Daniel J. Weeks (Editor), et al (2000); ISBN: 0880119756; http://www.amazon.com/exec/obidos/ASIN/0880119756/icongroupinterna
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Protein Expression in Down Syndrome Brain (Journal of Neural Transmission) by Gert Lubec (Editor) (2002); ISBN: 3211837329; http://www.amazon.com/exec/obidos/ASIN/3211837329/icongroupinterna
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Resource Pack for Carers of Adults with Down Syndrome and Dementia by Karen Dodd, et al (2002); ISBN: 1904082378; http://www.amazon.com/exec/obidos/ASIN/1904082378/icongroupinterna
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Schooling Children With Down Syndrome: Toward an Understanding of Possibility (Special Education Series (New York, N.Y.).) by Christopher Kliewer (1998); ISBN: 0807737313; http://www.amazon.com/exec/obidos/ASIN/0807737313/icongroupinterna
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Screening for Down Syndrome in the First Trimester by J. Gedis Grudzinskas (Editor), R. Humphry T. Ward (Editor) (1997); ISBN: 0902331981; http://www.amazon.com/exec/obidos/ASIN/0902331981/icongroupinterna
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Speech and Language Intervention in Down Syndrome by Jean Rondal, Sue Buckley (2003); ISBN: 1861562969; http://www.amazon.com/exec/obidos/ASIN/1861562969/icongroupinterna
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Taking Down Syndrome to School (Special Kids in School) by Jenna Glatzer, et al (2002); ISBN: 1891383191; http://www.amazon.com/exec/obidos/ASIN/1891383191/icongroupinterna
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Teaching Reading to Children With Down Syndrome: A Guide for Parents and Teachers (Topics in Down Syndrome) by Patricia Logan Oelwein (1995); ISBN: 0933149557; http://www.amazon.com/exec/obidos/ASIN/0933149557/icongroupinterna
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Teaching the Infant With Down Syndrome: A Guide for Parents and Professionals by Marci J. Hanson (1996); ISBN: 0890791031; http://www.amazon.com/exec/obidos/ASIN/0890791031/icongroupinterna
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Tears & Triumphs: A Look into the World of Children With Down Syndrome or Other Developmental Delays by Valentine Dmitriev, et al (1997); ISBN: 0897167155; http://www.amazon.com/exec/obidos/ASIN/0897167155/icongroupinterna
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The 2002 Official Parent's Sourcebook on Down Syndrome by James N. Parker, Icon Health Publications (2002); ISBN: 0597832005; http://www.amazon.com/exec/obidos/ASIN/0597832005/icongroupinterna
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The Book of Matthew: Our Baby Has Down Syndrome by John Breitling, et al; ISBN: 0933703945; http://www.amazon.com/exec/obidos/ASIN/0933703945/icongroupinterna
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The Down Syndrome Nutrition Handbook: A Guide to Promoting Healthy Lifestyles by Joan E. Guthrie Medlen, et al (2002); ISBN: 1890627232; http://www.amazon.com/exec/obidos/ASIN/1890627232/icongroupinterna
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The Molecular Biology of Down Syndrome (Journal of Neural Transmission, 57) by Gert Lubec (Editor) (2000); ISBN: 3211833781; http://www.amazon.com/exec/obidos/ASIN/3211833781/icongroupinterna
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The Morphogenesis of Down Syndrome: Proceedings of the National Down Syndrome Society Conference on Morphogenesis and Down Syndrome, Held in New York (Progress in Clinical and Biological Research, V. 373.) by National Down Syndrome Society Conference on Morphogenesis and Down Sy, et al; ISBN: 0471561681; http://www.amazon.com/exec/obidos/ASIN/0471561681/icongroupinterna
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The Neurobiology of Down Syndrome/#1682 by Charles J. Epstein (Editor); ISBN: 0881672289; http://www.amazon.com/exec/obidos/ASIN/0881672289/icongroupinterna
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The Phenotypic Mapping of Down Syndrome and Other Aneuploid Conditions: Proceedings of the National Down Syndome Society Conference Held in New York (Progress in Clinical and Biological Research, Vol 384) by Charles J. Epstein (Editor), National Down Syndrome Society; ISBN: 0471304492; http://www.amazon.com/exec/obidos/ASIN/0471304492/icongroupinterna
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The Psychobiology of Down Syndrome (Issues in the Biology of Language and Cognition) by Lynn Nadel (Editor); ISBN: 0262140438; http://www.amazon.com/exec/obidos/ASIN/0262140438/icongroupinterna
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The Young Child With Down Syndrome by Siegfried M. Pueschel (1984); ISBN: 0898851203; http://www.amazon.com/exec/obidos/ASIN/0898851203/icongroupinterna
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The Young Person With Down Syndrome: Transition from Adolescence to Adulthood by Siegfried M. Pueschel (Photographer); ISBN: 0933716907; http://www.amazon.com/exec/obidos/ASIN/0933716907/icongroupinterna
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Trisomy 21 Down's Syndrome: Research Perspectives by Felix De Lacruz; ISBN: 0839115881; http://www.amazon.com/exec/obidos/ASIN/0839115881/icongroupinterna
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Trisomy 21: An International Symposium, Convento Delle Clarisse, Rapallo, Italy, November 8-10, 1979 by De LA Cruz; ISBN: 0387106537; http://www.amazon.com/exec/obidos/ASIN/0387106537/icongroupinterna
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Understanding Down Syndrome: An Introduction for Parents by Cliff Cunningham (1996); ISBN: 1571290095; http://www.amazon.com/exec/obidos/ASIN/1571290095/icongroupinterna
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Yoga for the Special Child: A Therapeutic Approach for Infants and Children With Down Syndrome, Cerabral Palsy, and Learning Disabilities by Sonia Sumar, et al (1998); ISBN: 096580240X; http://www.amazon.com/exec/obidos/ASIN/096580240X/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Down syndrome” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •
Better healthcare for adults with Down syndrome: a guide for professionals, carers, and families on the health needs of adults with Down syndrome Author: Prasher, Vee P.; Year: 1964; Kidderminster, Worcs.: BILD, c2002; ISBN: 1902519205 http://www.amazon.com/exec/obidos/ASIN/1902519205/icongroupinterna
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First trimester prenatal testing for down syndrome using nuchal translucency Author: Institute for Clinical Systems Improvement. Technology Assessment Committee.; Year: 1964; [Bloomington, Minn.]: Institute for Clinical Systems Improvement, c2002
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Speech and language intervention in Down syndrome Author: Rondal, J. A.; Year: 2002; London: Whurr, 2003; ISBN: 1861562969 http://www.amazon.com/exec/obidos/ASIN/1861562969/icongroupinterna
11 In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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Chapters on Down Syndrome In order to find chapters that specifically relate to Down syndrome, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Down syndrome 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 “Down syndrome” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on Down syndrome: •
Alzheimer Disease: A Health Risk of Growing Older With Down Syndrome Source: in Nadel, L. Rosenthal, D. Down Syndrome: Living and Learning in the Community. New York, NY: Wiley-Liss, Inc. 1995. p. 58- 64. Contact: Available from Wiley-Liss, Inc. 605 Third Avenue, New York, NY 10158-0012. (212) 850-6000. PRICE: $17.95. ISBN: 0471022012. Summary: This chapter discusses the health risk of developing Alzheimer's disease (AD) in people with Down syndrome (DS) who live beyond the age of 40 years. It discusses the susceptibility of people with DS to acquiring AD. The author indicates that knowledge about AD's connection with age and DS is incomplete and no test or procedure yet can identify the presence of AD before the onset of clinical manifestations, or monitor the total range of deficits induced by AD. Additionally, diagnosis of AD in people with DS must rely on procedures developed for people without DS. The diagnostic procedures, which may involve several stages spread over several weeks or months and include neurological assessment, are not perfect. One New York study indicates the diagnosis of AD in people with DS was four to five times more common than in other developmentally challenged people of comparable age, level of function, health, and lifestyles. The author indicates that inaccurate diagnoses may hamper research studies that seek to establish the incidence and prevalence of AD, identify as yet unknown risk factors, and establish patterns of disease frequency and severity among family members and relatives. 29 references.
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Aging and Alzheimer's Disease in People With Down Syndrome Source: in Lott, I.T. McCoy, E.E. Down Syndrome: Advances in Medical Care. New York, NY: Wiley-Liss. 1992. p. 167-183. Contact: Available from Wiley-Liss. 605 Third Avenue, New York, NY 10158. (800) 8794539 or (212) 850-8888 (FAX). PRICE: $54.95 (cloth); $27.95 (paper). Summary: This book chapter, which was first presented as a paper at professional conference on medical care of Down syndrome, provides an overview of the relationship between Down syndrome and Alzheimer's disease. People with Down syndrome are at particularly high risk for Alzheimer's disease, and because they age faster than the general population, they are likely to develop Alzheimer's disease at a much earlier age. This is particularly true now that medical advances have tended to prolong the lifespan of persons with Down syndrome. The following specific topics are discussed in the chapter: delayed and abnormal clinical and neuropathological brain development in persons with Down syndrome; definition and assessment of dementia; differential diagnosis of the etiology of dementia in a person with Down syndrome; clinical signs of aging and Alzheimer's disease in Down syndrome individuals; aging
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and Alzheimer's disease neuropathology in Down syndrome individuals; and, genetic factors in Alzheimer's disease and Down syndrome. 99 references. •
Language Development in Children and Adolescents with Down Syndrome Source: in Miller, J.F. Leddy, M. Leavitt, L.A., eds. Improving the Communication of People with Down Syndrome. Baltimore, MD: Paul H. Brookes Publishing Company. 1999. p. 41-60. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775. Fax (410) 337-8539. E-mail:
[email protected]. Website: www.brookespublishing.com. PRICE: $34.95 plus shipping and handling. ISBN: 1557663505. Summary: This chapter from a book about assessing and treating speech, language, and communication problems in children and adults with Down syndrome summarizes cross-sectional research on language development in older children and adolescents with Down syndrome. The research focuses on three areas: whether children with Down syndrome have a characteristic pattern of specific language impairment (SLI) relative to expectations based on their mental age (MA); how the gap between the language comprehension skills and language production skills of children with Down syndrome changes with age; and the processes of language acquisition that are associated with individual variations in language skills among these children. The section on language comprehension covers findings in the areas of vocabulary and syntax comprehension; the section on cognition discusses pervasive sequencing impairment and auditory shortterm memory impairment. Other topics include hearing status, language production, expressive language impairments, the Critical Period hypothesis, grammatical morpheme impairment, and language acquisition processes. The author concludes with a discussion of the implications of this research for intervention with children and adolescents with Down syndrome. 5 tables. 36 references.
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Assistive Technology: Strategies and Tools for Enhancing the Communication Skills of Children with Down Syndrome Source: in Miller, J.F. Leddy, M. Leavitt, L.A., eds. Improving the Communication of People with Down Syndrome. Baltimore, MD: Paul H. Brookes Publishing Company. 1999. p. 161-204. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775. Fax (410) 337-8539. E-mail:
[email protected]. Website: www.brookespublishing.com. PRICE: $34.95 plus shipping and handling. ISBN: 1557663505. Summary: This chapter from a book about assessing and treating speech, language, and communication problems in children and adults with Down syndrome discusses the use of assistive technology in this population. The authors focus on the use of computers and communication aids as assistive technology (AT) tools that help those with Down syndrome achieve their maximum communication potential. Specifically, these AT tools can help children with Down syndrome develop skills and perform communication behaviors that are particularly challenging to them. The chapter focuses on AT as it supports six communication behaviors: enhancing thinking skills related to communication development; learning to use symbols (i.e., words) for communicating; using alternate methods to express ideas when speech is difficult to understand; learning to use words in combination to create longer sentences; learning to understand sentences of greater length; and establishing social relationships with peers. The authors
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outline the helpful features of computers and other communication aids for teaching children with Down syndrome, and present case studies that demonstrate the use of these AT tools. 12 figures. 1 table. 67 references. •
Enhancing the Speech and Language Skills of Adults with Down Syndrome Source: in Miller, J.F. Leddy, M. Leavitt, L.A., eds. Improving the Communication of People with Down Syndrome. Baltimore, MD: Paul H. Brookes Publishing Company. 1999. p. 205-216. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775. Fax (410) 337-8539. E-mail:
[email protected]. Website: www.brookespublishing.com. PRICE: $34.95 plus shipping and handling. ISBN: 1557663505. Summary: This chapter from a book about assessing and treating speech, language, and communication problems in children and adults with Down syndrome discusses strategies to enhance the speech and language skills of adults with Down syndrome. The authors report on their findings from communication assessments conducted in this population. The authors stress that, contrary to general pessimism about improving communication in an adult population, their work showed that speech and language skills could be improved and that this improvement could also be seen during communication at home and outside the clinical setting. The communication assessments showed that most adults with Down syndrome evidenced strengths in the following areas: visual memory, vocabulary and semantics, the use of reading and writing, the use of hand signs and gestures to communicate, and the motivation to communicate. The authors describe how to use their strengths to address the typical challenges of reduced speech intelligibility, difficulties with auditory memory and comprehension, and poor grammatical construction skills. The authors conclude with a brief discussion of age factors, noting that young adults who participated in treatment were very different from the older adults.
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View Toward the Future: Improving the Communication of People with Down Syndrome Source: in Miller, J.F. Leddy, M. Leavitt, L.A., eds. Improving the Communication of People with Down Syndrome. Baltimore, MD: Paul H. Brookes Publishing Company. 1999. p. 241-262. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775. Fax (410) 337-8539. E-mail:
[email protected]. Website: www.brookespublishing.com. PRICE: $34.95 plus shipping and handling. ISBN: 1557663505. Summary: This final chapter from a book about assessing and treating speech, language, and communication problems in children and adults with Down syndrome considers future possibilities for improving the communication of people with Down syndrome. The authors note that there is reason to be optimistic about the future for people with Down syndrome in communication, educational opportunities, and community involvement, but caution that the future role of language and communication skills in society in general must also be evaluated (i.e., the increasing demand for language, communication, and literacy skills in American society). The authors provide a summary of expectations for communication development among people with Down syndrome, drawn from the research literature to date. This summary focuses on what
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needs attention early in these individuals development if their environments are to be optimized to establish a firm foundation for their future learning. 2 tables. 30 references. •
Down Syndrome: The Impact of Speech Production on Language Development Source: in Paul, R., ed. Exploring the Speech-Language Connection. Baltimore, MD: Paul H. Brookes Publishing Company. 1998. p. 163-177. Contact: Available from Paul H. Brookes Publishing Company. P.O. Box 10624, Baltimore, MD 21285-0624. (800) 638-3775. Fax (410) 337-8539. E-mail:
[email protected]. Website: www.brookespublishing.com. PRICE: $42.00 plus shipping and handling. ISBN: 1557663254. Summary: This chapter is from a textbook that investigates the various connections between the earliest human sounds and subsequent language development. This chapter describes impairments in the speech production mechanism of children with Down syndrome and discusses their implications for language learning and oral communication. Topics include an overview of the Down syndrome population, including neurological characteristics, cognitive skills, speech skills, and language skills; speech production mechanisms, including the skeletal system, muscular system, and nervous system; the causes of dysfluent speech production, including the speech motor basis for stuttering, and the cluttering or language-based hypothesis; speech intelligibility; and how speech production impairments influence language and communication performance. The authors conclude that both unintelligible and dysfluent speech have adverse effects on language and communication performance in children with Down syndrome. However, both behaviors are amenable to intervention in children and adults with Down syndrome. 64 references.
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Health Supervision for Children with Down Syndrome Source: in Committee on Genetics, American Academy of Pediatrics. Genetic Disorders and Birth Defects: A Compendium of AAP Guidelines and Resources for the Primary Care Practitioner. Elk Grove Village, IL: American Academy of Pediatrics (AAP). 1997. p. 16-20.AV.Available from American Academy of Pediatrics (AAP). 141 Northwest Point Boulevard, Elk Grove Village, IL 60007-1098. (800) 433-9016 (members) or (888) 227-1773 (nonmembers). Fax (847) 434-8000. Website: www.aap.org. PRICE: $24.95 each (members); $29.95 each (nonmembers); plus shipping and handling. Order Number BMA0097. Contact: Available from American Academy of Pediatrics. Division of Publications, 141 Northwest Point Boulevard, P.O. Box 927, Elk Grove Village, IL 60009-0927. (800) 4339016 or (847) 228-5005. Fax (847) 228-1281. Website: www.aap.org. PRICE: $24.95 each (members); $29.95 each (nonmembers); plus shipping and handling. Order Number BMA0097. Summary: This chapter on health supervision for children with Down syndrome is from a compendium of the American Academy of Pediatrics (AAP) guidelines and resources for physicians who are working with patients who have genetic disorders and birth defects. The compendium serves as a diagnostic and management resource guide for pediatricians and primary care physicians. This chapter offers guidelines designed to assist the pediatrician in caring for the child in whom the diagnosis of Down syndrome has been confirmed by karyotype. The introductory section reviews the symptoms and complications of Down syndrome and notes several areas that will require ongoing assessment through childhood and adolescence. The guidelines then outline strategies for the prenatal visit (some pregnant women are referred for consultation), health
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supervision for newborns (birth to one month), infants (one month to one year), early childhood (one to five years), late childhood (five to thirteen years), and adolescence to early adulthood (thirteen years to twenty-one years or older). Each section notes recommendations for examination and anticipatory guidance. The statement emphasizes that medical management, home environment, education, and vocational training can significantly affect the level of functioning of children and adolescents with Down syndrome and facilitate their transition to adulthood. The guidelines conclude with a brief list of recommended resources for new parents. 14 references. •
Ear, Nose, and Sinus Conditions of Children with Down Syndrome Source: in Van Dyke, D.C., et al., eds. Medical and Surgical Care for Children with Down Syndrome: A Guide for Parents. Bethesda, MD: Woodbine House. 1995. p. 155174. Contact: Available from Woodbine House. 6510 Bells Mill Road, Bethesda, MD 20817. (800) 843-7323 or (301) 897-3570; Fax (301) 897-5838. PRICE: $14.95 plus shipping and handling. ISBN: 0933149549. Summary: This chapter, from a guide for parents of children with Down syndrome, discusses ear, nose, and sinus conditions typical in this population. The author notes that for typical ear, nose, and throat conditions, treatment for children with Down syndrome is the same as for other children. The author focuses on those circumstances in which special considerations exist. Topics covered include the impact of hearing loss on language development, how hearing impairments are classified, the causes of hearing loss, hearing loss treatment options, neck instability, breathing concerns, tonsillectomy, sinusitis, tongue protrusion, and drooling. 4 figures. 1 table. 8 references.
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Down Syndrome: Trisomy 21, Mongolism 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. 66-73. 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: Down syndrome is one of the most common causes of generalized developmental delay and mild to moderate mental retardation. This chapter on Down syndrome 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 characteristic features of the disorder; orthopedic and skeletal problems, neurological problems, sensory problems, 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. 1 figure. 15 references.
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Down Syndrome and the Gastrointestinal Tract Source: in Van Dyke, D.C., et al., eds. Medical and Surgical Care for Children with Down Syndrome: A Guide for Parents. Bethesda, MD: Woodbine House, Inc. 1995. p. 175-188.
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Contact: Available from Woodbine House, Inc. 6510 Bells Mill Road, Bethesda, MD 20817. (800) 843-7323. PRICE; $14.95. ISBN: 0933149549. Summary: This chapter, from a guide for parents of children with Down syndrome, discusses Down syndrome and the gastrointestinal (GI) tract. The authors review the most common and serious GI problems and explain their symptoms and treatment. Topics include the prevalence of anatomical anomalies, aganglionic megacolon (Hirschsprung's disease), annular pancreas, duodenal atresia and duodenal stenosis, imperforate anus, pyloric stenosis, tracheo-esophageal fistula, esophageal motility disorders, gastroesophageal reflux disease (GERD), and malabsorption syndromes. The authors encourage parents to use an interdisciplinary approach to the special health care needs of children with Down syndrome. 12 references. •
Dental Concerns of Children with Down Syndrome Source: in Van Dyke, D.C., et al, eds. Medical and Surgical Care for Children with Down Syndrome: A Guide for Parents. Bethesda, MD: Woodbine House. 1995. p. 229-251. Contact: Available from Woodbine House. 6510 Bells Mill Road, Bethesda, MD 20817. (800) 843-7323 or (301) 897-3570; Fax (301) 897-5838. PRICE: $14.95 plus shipping and handling. ISBN: 0933149549. Summary: Appropriate and early oral hygiene and care are essential for children with Down syndrome. This chapter, from a parent's guide to medical and surgical care for children with Down syndrome, reviews the best methods of dental care for these children and explains how to find good dental care. Topics covered include general oral and dental development and the differences in the mouth and teeth of children with Down syndrome, including xerostomia and tooth eruption; dental disease, including dental caries and periodontal disease; the role of early dental intervention; the elements of good dental care, including toothbrushing, anti-cavity treatments, diet, sealants, mouthwashes and rinses, and dental visits; choosing and working with a dentist; and orthodontics. The chapter concludes with a list of resources for parents who wish to obtain additional information. 3 figures. 11 references.
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Trisomy 21 (Down's Syndrome): a Model for the Study of Alzheimer's Disease Source: in Courtois, Y., et al., eds. Modern Trends in Aging Research: Proceedings of the International INSERM-EURAGE Symposium 'Modern Trends in Aging, Research, Gerontology and Geriatrics' held in Paris, March 1986. London, England: John Libbey and Company. 1986. p. 73-76. Contact: Available from John Libbey and Company. 80/84 Bondway, London SW8 1SF, ENGLAND. (71) 582-5266. ISBN: 086916103X. PRICE: Call for information. Summary: This paper summaries available evidence supporting the rationale of considering Down's syndrome (DS) as a model for studying and understanding Alzheimer's disease (AD). It is pointed out that adults with DS get a form of dementia that appears like AD, and all such adults over age 30 have the typical brain lesions of AD, plaques and tangles. It is suggested that the excess of one or more genes located on chromosome 21 may induce AD brain lesions, and that a possible strategy for studying the pathogenesis of AD is to isolate genes of chromosome 21 and introduce them into cells of appropriate test animals such as transgenic mice. Genetic research along these lines is discussed, supporting this proposed research approach. 14 references.
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Directories In addition to the references and resources discussed earlier in this chapter, a number of directories relating to Down syndrome have been published that consolidate information across various sources. The Combined Health Information Database lists the following, which you may wish to consult in your local medical library:12 •
Self-Help Sourcebook: Finding and Forming Mutual Aid Self-Help Groups. 4th ed Source: Denville, NJ: American Self-Help Clearinghouse. 1992. 226 p. Contact: Available from American Self-Help Clearinghouse. Attn: Sourcebook, St. Clares-Riverside Medical Center, 25 Pocono Road, Denville, NJ 07834. Voice (201) 6257101; TTY (201) 625-9053. PRICE: $9.00 book rate; $10.00 first class mail. ISBN: 0963432206. Summary: This sourcebook lists self-help groups in a wide variety of topic areas, including addictions and dependencies, bereavement, disabilities, health, mental health, parenting and family, physical and/or emotional abuse, and miscellaneous categories. Topics relevant to deafness and communication disorders include acoustic neuroma, alternative/augmentative communication, autism, cleft palate and cleft lip, cochlear implants, developmental disabilities, developmentally delayed children, down syndrome, dystonia, ear anomalies, elective mutism, hearing impairment, inner ear problems, laryngectomy, late-deafened adults, learning disabilities, Meniere's disease, neck-head-oral cancer, parents of children with hearing impairment, speech dysfunction, speech impairments, stuttering, tinnitus, Tourette syndrome, and Usher's syndrome. In addition to basic information about the self-help groups, the sourcebook lists self-help clearinghouses, toll-free helplines, resources for rare disorders, resources for genetic disorders, housing and neighborhood resources and resources for the homeless, how-to ideas for developing self-help groups, and using a home computer for mutual help. The book includes a bibliography and key word index.
12
You will need to limit your search to “Directory” and “down syndrome” using the "Detailed Search" option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find directories, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Select your preferred language and the format option “Directory.” Type “down syndrome” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months.
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CHAPTER 8. MULTIMEDIA ON DOWN SYNDROME Overview In this chapter, we show you how to keep current on multimedia sources of information on Down syndrome. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on Down syndrome is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “Down syndrome” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, 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 “Videorecording (videotape, videocassette, etc.).” Type “Down syndrome” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on Down syndrome: •
Hi Buddy: The Developmentally Delayed Individual With Alzheimer Disease Source: Baltimore, MD: Video Press. 1998. (videocassette). Contact: Available from Video Press. 100 N Greene Street, Suite 300, Baltimore, MD 21201. (800) 328-7450; (410) 706-5497; FAX (410) 706-8471. PRICE: $200.00. Summary: This videotape tells the story of Roger, a 53-year-old man with Down syndrome (DS) who is in the early stages of Alzheimer's disease (AD). The purpose is to help other families and caregivers understand and recognize the signs of AD in an aging person with DS, and learn how to help that person live as independently as possible for as long as possible. As the viewer watches Roger interacting with his caregiver and friends at home and work, the narrator describes some of the early symptoms to look for. The caregiver talks with a specialist in mental retardation and dementing illness, and explains some of changes she has noticed in Roger. He has started to become frustrated more easily, has lost his previously hearty appetite, is having trouble speaking and understanding others, has difficulty sleeping, and is often disoriented. The
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video also talks about the higher risk of AD in people with DS, how the physician can help make the diagnosis of AD, what to do if the person has a seizure, what will happen as the disease progresses, and how to make modifications at work to make the job less demanding. •
An inside look: Helping parents receive a difficult diagnosis Source: [Portland, ME:} Parents in Partnership. ca. 1993. 1 videotape (VHS 1/2 inch). Contact: Available from Parents in Partnership, University of Southern Maine, Public Policy and Management Program In Human Resources, Portland, ME 04103. Telephone: (207) 780-4430. Summary: This videotape is an edited version of a pediatrics grand round at the Maine Medical Center in Portland. It presents three stories by parents who discuss the experience of receiving a difficult diagnosis about their child, how they were well or not well supported by health professionals, and the difficulties they had in communicating their concerns to health professionals at later periods during the child's life. The conditions the children had included down syndrome, premature birth with long hospitalizations, and multiple developmental problems with no clear diagnosis. [Funded by the Maternal and Child Health Bureau].
Bibliography: Multimedia on Down Syndrome The National Library of Medicine is a rich source of information on healthcare-related multimedia productions including slides, computer software, and databases. To access the multimedia database, go to the following Web site: http://locatorplus.gov/. Select “Search LOCATORplus.” Once in the search area, simply type in Down syndrome (or synonyms). Then, in the option box provided below the search box, select “Audiovisuals and Computer Files.” From there, you can choose to sort results by publication date, author, or relevance. The following multimedia has been indexed on Down syndrome: •
Down syndrome [videorecording]: optimizing health and development Source: a production of VES, Video Educational Services; Year: 1992; Format: Videorecording; Amherst, NY: VES, c1992
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CHAPTER 9. SYNDROME
PERIODICALS AND NEWS ON DOWN
Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Down syndrome.
News Services and Press Releases One of the simplest ways of tracking press releases on Down syndrome 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 “Down syndrome” (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 Down syndrome. 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 “Down syndrome” (or synonyms). The following was recently listed in this archive for Down syndrome: •
Early screening may help detect Down syndrome Source: Reuters Health eLine Date: October 08, 2003 http://www.reutershealth.com/archive/2003/10/08/eline/links/20031008elin013.htm l
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•
Amniotic fluid PCR helpful in Down syndrome screening Source: Reuters Medical News Date: May 23, 2003
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Risk of Down syndrome linked to other birth defects Source: Reuters Health eLine Date: April 18, 2003
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'Quadruple' test may better Down syndrome screening Source: Reuters Health eLine Date: March 07, 2003
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Second-trimester biochemical and ultrasound screening accurately detects Down syndrome Source: Reuters Medical News Date: December 27, 2002
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First trimester sonography better than later for detection of Down syndrome Source: Reuters Medical News Date: December 20, 2002
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Fetal nasal bone appearance on ultrasound may guide Down syndrome detection Source: Reuters Medical News Date: November 07, 2002
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Microarray technology may lead to improved assay for fetal Down syndrome Source: Reuters Medical News Date: September 05, 2002
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Blood flow test may improve Down syndrome detection Source: Reuters Health eLine Date: August 29, 2002
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Oncogenic transcription factor initiates path leading to leukemia in Down syndrome Source: Reuters Medical News Date: August 14, 2002
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Gene behind Down syndrome-linked cancer Source: Reuters Health eLine Date: August 12, 2002
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Use of four serum markers improve the accuracy of detecting Down syndrome Source: Reuters Medical News Date: July 19, 2002
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New Down syndrome screening test no better than old Source: Reuters Health eLine Date: July 05, 2002
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Life expectancy for Down syndrome patients doubled in US over last two decades Source: Reuters Medical News Date: March 21, 2002
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Screen could allow earlier Down syndrome detection Source: Reuters Health eLine Date: January 17, 2002
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Noninvasive screening method could allow earlier Down syndrome detection Source: Reuters Medical News Date: January 17, 2002
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Down syndrome study provides Alzheimer's clues Source: Reuters Health eLine Date: December 13, 2001
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Test can screen for Down syndrome in 1st trimester Source: Reuters Health eLine Date: November 16, 2001
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UK clinics don't offer best Down syndrome tests Source: Reuters Health eLine Date: August 24, 2001
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High altitude travel risky for Down syndrome child Source: Reuters Health eLine Date: August 06, 2001
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Treatment outcome of AMKL is often poor in absence of Down syndrome Source: Reuters Medical News Date: July 09, 2001
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New test said to detect Down syndrome in embryos Source: Reuters Health eLine Date: July 03, 2001
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Survival of US patients with Down syndrome differs by ethnicity Source: Reuters Medical News Date: June 07, 2001
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•
Blacks with Down syndrome have shorter life span Source: Reuters Health eLine Date: June 07, 2001
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Down syndrome screen less accurate in short women Source: Reuters Health eLine Date: May 01, 2001
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Piracetam shows no benefit for Down syndrome Source: Reuters Industry Breifing Date: April 30, 2001
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Drug shows no benefit for Down syndrome Source: Reuters Health eLine Date: April 30, 2001
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Ultrasound findings may not predict Down syndrome Source: Reuters Health eLine Date: February 28, 2001
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Second-trimester ultrasonography impractical screening test for Down syndrome Source: Reuters Medical News Date: February 27, 2001
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Age threshold for Down syndrome testing questioned Source: Reuters Health eLine Date: January 18, 2001
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Down syndrome screening accuracy can be improved Source: Reuters Medical News Date: December 04, 2000
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Impact of maternal age on Down syndrome risk affected by ethnicity Source: Reuters Medical News Date: November 23, 2000
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Cluster of Down syndrome cases in Ireland investigated Source: Reuters Health eLine Date: November 14, 2000
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Women's attitudes toward Down syndrome testing vary Source: Reuters Health eLine Date: October 09, 2000
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Women's attitudes toward prenatal testing for Down syndrome vary widely Source: Reuters Medical News Date: October 06, 2000
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Researchers study earlier screening for Down syndrome Source: Reuters Health eLine Date: September 12, 2000
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Combination screening improves first-trimester detection of Down syndrome Source: Reuters Medical News Date: August 09, 2000
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Combination of tests allows earlier Down syndrome diagnosis Source: Reuters Health eLine Date: August 07, 2000
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Maternal urine assay aids detection of Down syndrome fetus Source: Reuters Medical News Date: June 01, 2000
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Old test as good as new for Down syndrome Source: Reuters Health eLine Date: March 03, 2000
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Mouse provides clue to Down syndrome Source: Reuters Health eLine Date: February 25, 2000
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Levels of serum markers for Down syndrome differ in IVF pregnancies Source: Reuters Medical News Date: January 07, 2000
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Down syndrome risk linked to abnormal maternal folate metabolism Source: Reuters Medical News Date: September 29, 1999
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Down syndrome linked to abnormal gene in mothers Source: Reuters Health eLine Date: September 28, 1999
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APOE-e2 allele protects against Alzheimer's disease in Down syndrome patients Source: Reuters Medical News Date: August 27, 1999
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Numerous defects common in older Down syndrome patients Source: Reuters Medical News Date: July 29, 1999
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Third-trimester ultrasound abnormalities help identify fetuses with Down syndrome Source: Reuters Medical News Date: May 18, 1999
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Alzheimer's drug may treat Down syndrome Source: Reuters Health eLine Date: March 26, 1999
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Treadmills help Down syndrome kids walk sooner Source: Reuters Health eLine Date: March 19, 1999
•
Algorithm based on ultrasound, urine measurements has "high" sensitivity for Down syndrome Source: Reuters Medical News Date: March 11, 1999 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 “Down syndrome” (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.
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Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Down syndrome” (or synonyms). If you know the name of a company that is relevant to Down syndrome, 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 “Down syndrome” (or synonyms).
Newsletters on Down Syndrome Find newsletters on Down syndrome using the Combined Health Information Database (CHID). You will need to use the “Detailed Search” option. To access CHID, go to the following hyperlink: http://chid.nih.gov/detail/detail.html. Limit your search to “Newsletter” and “Down syndrome.” Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter.” Type “Down syndrome” (or synonyms) into the “For these words:” box. The following list was generated using the options described above: •
Dimensions. [Newsletter] Source: Seattle, WA: University of Washington Alzheimer's Disease Center. 1986. [6 p. average]. Contact: Available from University of Washington Alzheimer's Disease Center. RP-10, Seattle, WA 98195. (206) 543-1871. PRICE: Free. Summary: This six-page quarterly newsletter provides general information about Alzheimer's disease, along with information about events at the Alzheimer's Disease Center (ADC) at the University of Washington in Seattle. Each issue also includes a question and answer column and a guest column written by a representative of one of the Alzheimer's groups in the state. The Spring 1992 issue included articles about the opening of a satellite ADC clinic in King County, Washington; research on connections between Down syndrome and Alzheimer's disease; and a description of the ADC training program for nursing home staff.
•
Introducing the Idea Exchange: Home-to-School Communication Source: Disability Solutions. 4(2): 1-15. March-April 2000. Contact: Available from Disability Solutions. PMB 179, 9220 S.W. Barbur Boulevard, Number 119, Portland, OR 97219.
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Summary: This issue of the Disability Solutions newsletter, a publication for families and others interested in Down syndrome and related disabilities, is the first to introduce the Idea Exchange. The Idea Exchange offers a way for parents and professionals to share practical strategies that are successful. This installment gathers ideas for home to school communication systems parents have designed with their IEP (Individualized Education Plan) teams across the country. The lead story explains the rationale for home to school communication stories, and introduces a notebook style format for the actual communication method. A second article explains methods for families to design home to school communication systems that the child can complete his or her own record keeping. The issue includes photographs and reprints of the communication devices and forms used. The editorial introduction to the issue reminds readers to check the Idea Exchange section of the organization's website for more ideas (www.disabilitysolutions.org/idea.htm). A list of resources and their manufacturers is also included. 18 figures. •
Assistive Technology: Putting the Puzzle Together Source: Disability Solutions. 3(2): 1-16. July-August 1998. Contact: Available from Disability Solutions. 9220 S.W. Barbur Boulevard, Number 119179, Portland, OR 97219-5428. (503) 224-7662. Fax (503) 246-3869. E-mail:
[email protected]. Website: www.teleport.com/~dsolns. Summary: This issue of the Disability Solutions newsletter focuses on the use of assistive technology for families and others interested in Down syndrome and related disabilities. Assistive technology is defined as anything that can help a person with a disability do something they cannot do or that can help them to do it better than they can without it. Assistive technology ranges from lengthened light switches, to wheelchairs, to adaptive equipment, to computer software. Assistive technology is available to help with spoken communication, written communication, mobility, seeing, reading, eating, feeding, hearing, dressing, and playing. Topics include the array of devices that are considered assistive technology, the Abledata Database, how to learn about assistive technology, assistive technology in the classroom, the assistive technology evaluation, and organizations and resources that can help. The newsletter also includes the Wisconsin Assistive Technology Initiative Assistive Technology Checklist, a comprehensive list of assistive technology strategies and devices. The final three pages of the newsletter list resource organizations for readers who wish to obtain additional information or assistance.
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “Down syndrome” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on Down syndrome:
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•
Teaching Sign Language Source: Disability Solutions. 2(5): 1, 3-8. January-February 1998. Contact: Available from Disability Solutions. 9220 Southwest Barbur Boulevard, Number 119-179, Portland, OR 97219-5428. (503) 244-7662; Fax (503) 246-3869; E-mail:
[email protected]; http://www.teleport.com/~dsolns. Summary: This article describes the use of sign language to augment communication for children who are deaf, have a hearing loss, have oral-motor difficulties, or have developmental disabilities. The article is from a newsletter for families and others interested in Down syndrome and related disabilities. The author first describes the differences between American Sign Language (ASL) and Signed English, including total communication. The author notes that young children with Down syndrome are usually excellent communicators. They use facial expressions, gestures, mime, and vocalizations to express their ideas. Because spoken language often develops more slowly than receptive language or a desire to communicate, sign language is often the tool they need to build their confidence in communicating. The author encourages parents to start using sign language and provides specific examples of how to begin. Topics include choosing signs, common early signs children learn and use, signs to be introduced later, strategies for incorporating sign language into every day activities, and where to find additional resources. The article is illustrated with line drawings of signers making common signs (the word they represent is also noted). A page listing recommended resources is appended to the article.
Academic Periodicals covering Down Syndrome Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Down syndrome. In addition to these sources, you can search for articles covering Down syndrome that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute13: •
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/
13
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
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
•
National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
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
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
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.14 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:15 •
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
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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
14
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). 15 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 Combined Health Information Database
A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “Down syndrome” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “Down syndrome” (or synonyms) into the “For these words:” box. The following is a sample result: •
Increased Risk of Alzheimer's Disease in Mothers of Adults With Down's Syndrome Source: Lancet. 344(8919): 353-356. August 6, 1994. Summary: This study compared the frequency of Alzheimer's disease (AD) in parents of adults with Down syndrome (DS) and in parents of adults with other forms of mental retardation. Researchers postulated an increased frequency of dementia among mothers who were age 35 or younger compared with mothers who were older than 35 when their children with DS were born and compared with mothers of people with other forms of mental retardation. Fathers of adults with DS were not expected to have an increased risk of dementia. Families of 96 adults with DS and families of 80 adults with other forms of mental retardation were located through the New York State Developmental Disabilities services network. A semi-structured interview was used to obtain information on the presence or absence of non-stroke-related dementia and other disorders in parents. Findings show an increase in risk of dementia among mothers of DS children compared with the control mothers. The risk of dementia among mothers who were 35 years old or younger when their DS children were born was five times that of the control subjects mothers. There was no increase in risk of dementia among mothers who were over 35 years old at their children's births. There was no difference in risk of dementia between fathers of DS cases and fathers of control subjects and no discernible influence of age on this risk. Familial aggregation of dementia among mothers of adults with DS supports the hypothesis of a shared genetic susceptibility to DS and AD. 1 figure, 2 tables, 26 references.
•
Early intervention: Child development and family adaptation Source: Arlington, VA: National Center for Education in Maternal and Child Health. 1993. 10 pp. Contact: Available from Librarian, National Center for Education in Maternal and Child Health, 2000 15th Street, North, Suite 701, Arlington, VA 22201-2617. Telephone: (703) 524-7802 / fax: (703) 524-9335 / e-mail:
[email protected] / Web site: http://www.ncemch.org. Photocopy available at no charge; also available from the Web site at no charge.
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Summary: This report summarizes a Maternal and Child Health Bureau project on the efficacy of early intervention services to families and family adaptations presented at a seminar December 2, 1993. The study focused on three target groups: children with down syndrome, children with motor impairments, and children with developmental delays. The report concludes with reaction to the project and a list of references. [Funded by the Maternal and Child Health Bureau].
The NLM Gateway16 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.17 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Down syndrome” (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 14295 407 42 23 2 14769
HSTAT18 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.19 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.20 Simply search by “Down syndrome” (or synonyms) at the following Web site: http://text.nlm.nih.gov. 16
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
17
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). 18 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 19 20
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 Biologists21 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.22 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.23 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
The Genome Project and Down Syndrome In the following section, we will discuss databases and references which relate to the Genome Project and Down syndrome. Online Mendelian Inheritance in Man (OMIM) The Online Mendelian Inheritance in Man (OMIM) database is a catalog of human genes and genetic disorders authored and edited by Dr. Victor A. McKusick and his colleagues at Johns Hopkins and elsewhere. OMIM was developed for the World Wide Web by the National Center for Biotechnology Information (NCBI).24 The database contains textual information, pictures, and reference information. It also contains copious links to NCBI’s Entrez database of MEDLINE articles and sequence information. 21 Adapted 22
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. 23 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. 24 Adapted from http://www.ncbi.nlm.nih.gov/. Established in 1988 as a national resource for molecular biology information, NCBI creates public databases, conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information--all for the better understanding of molecular processes affecting human health and disease.
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To search the database, go to http://www.ncbi.nlm.nih.gov/Omim/searchomim.html. Type “Down syndrome” (or synonyms) into the search box, and click “Submit Search.” If too many results appear, you can narrow the search by adding the word “clinical.” Each report will have additional links to related research and databases. In particular, the option “Database Links” will search across technical databases that offer an abundance of information. The following is an example of the results you can obtain from the OMIM for Down syndrome: •
Cataracts, Congenital, with Sensorineural Deafness, Down Syndrome-like Facial Appearance, Short Stature, and Mental Retardation Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601088
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Down Syndrome Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?190685
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Down Syndrome Cell Adhesion Molecule Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602523
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Down Syndrome Critical Region Gene 1 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602917
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Down Syndrome Critical Region Gene 1-like 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605860
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Down Syndrome Critical Region Gene 2 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605296
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Down Syndrome Critical Region Gene 3 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605298
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Down Syndrome Critical Region Gene 4 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?604829
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Down Syndrome Critical Region Gene 5 Web site: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?605938 Genes and Disease (NCBI - Map)
The Genes and Disease database is produced by the National Center for Biotechnology Information of the National Library of Medicine at the National Institutes of Health. This Web site categorizes each disorder by system of the body. Go to http://www.ncbi.nlm.nih.gov/disease/, and browse the system pages to have a full view of important conditions linked to human genes. Since this site is regularly updated, you may wish to revisit it from time to time. The following systems and associated disorders are addressed: •
Cancer: Uncontrolled cell division. Examples: Breast and ovarian cancer, Burkitt lymphoma, chronic myeloid leukemia, colon cancer, lung cancer, malignant melanoma, multiple endocrine neoplasia, neurofibromatosis, p53 tumor suppressor, pancreatic cancer, prostate cancer, Ras oncogene, RB: retinoblastoma, von Hippel-Lindau syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Cancer.html
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Immune System: Fights invaders. Examples: Asthma, autoimmune polyglandular syndrome, Crohn’s disease, DiGeorge syndrome, familial Mediterranean fever, immunodeficiency with Hyper-IgM, severe
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combined immunodeficiency. Web site: http://www.ncbi.nlm.nih.gov/disease/Immune.html •
Metabolism: Food and energy. Examples: Adreno-leukodystrophy, atherosclerosis, Best disease, Gaucher disease, glucose galactose malabsorption, gyrate atrophy, juvenile-onset diabetes, obesity, paroxysmal nocturnal hemoglobinuria, phenylketonuria, Refsum disease, Tangier disease, Tay-Sachs disease. Web site: http://www.ncbi.nlm.nih.gov/disease/Metabolism.html
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Muscle and Bone: Movement and growth. Examples: Duchenne muscular dystrophy, Ellis-van Creveld syndrome, Marfan syndrome, myotonic dystrophy, spinal muscular atrophy. Web site: http://www.ncbi.nlm.nih.gov/disease/Muscle.html
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Nervous System: Mind and body. Examples: Alzheimer disease, amyotrophic lateral sclerosis, Angelman syndrome, Charcot-Marie-Tooth disease, epilepsy, essential tremor, fragile X syndrome, Friedreich’s ataxia, Huntington disease, Niemann-Pick disease, Parkinson disease, Prader-Willi syndrome, Rett syndrome, spinocerebellar atrophy, Williams syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Brain.html
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Signals: Cellular messages. Examples: Ataxia telangiectasia, Cockayne syndrome, glaucoma, male-patterned baldness, SRY: sex determination, tuberous sclerosis, Waardenburg syndrome, Werner syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Signals.html
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Transporters: Pumps and channels. Examples: Cystic fibrosis, deafness, diastrophic dysplasia, Hemophilia A, long-QT syndrome, Menkes syndrome, Pendred syndrome, polycystic kidney disease, sickle cell anemia, Wilson’s disease, Zellweger syndrome. Web site: http://www.ncbi.nlm.nih.gov/disease/Transporters.html Entrez
Entrez is a search and retrieval system that integrates several linked databases at the National Center for Biotechnology Information (NCBI). These databases include nucleotide sequences, protein sequences, macromolecular structures, whole genomes, and MEDLINE through PubMed. Entrez provides access to the following databases: •
3D Domains: Domains from Entrez Structure, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Books: Online books, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=books
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Genome: Complete genome assemblies, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Genome
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NCBI’s Protein Sequence Information Survey Results: Web site: http://www.ncbi.nlm.nih.gov/About/proteinsurvey/
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Nucleotide Sequence Database (Genbank): Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Nucleotide
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OMIM: Online Mendelian Inheritance in Man, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
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PopSet: Population study data sets, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Popset
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ProbeSet: Gene Expression Omnibus (GEO), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=geo
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Protein Sequence Database: Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Protein
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PubMed: Biomedical literature (PubMed), Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
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Structure: Three-dimensional macromolecular structures, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Structure
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Taxonomy: Organisms in GenBank, Web site: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Taxonomy
To access the Entrez system at the National Center for Biotechnology Information, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=genome, and then select the database that you would like to search. The databases available are listed in the drop box next to “Search.” Enter “Down syndrome” (or synonyms) into the search box and click “Go.” Jablonski’s Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes Database25 This online resource has been developed to facilitate the identification and differentiation of syndromic entities. Special attention is given to the type of information that is usually limited or completely omitted in existing reference sources due to space limitations of the printed form. At http://www.nlm.nih.gov/mesh/jablonski/syndrome_toc/toc_a.html, you can search across syndromes using an alphabetical index. Search by keywords at http://www.nlm.nih.gov/mesh/jablonski/syndrome_db.html. The Genome Database26 Established at Johns Hopkins University in Baltimore, Maryland in 1990, the Genome Database (GDB) is the official central repository for genomic mapping data resulting from the Human Genome Initiative. In the spring of 1999, the Bioinformatics Supercomputing Centre (BiSC) at the Hospital for Sick Children in Toronto, Ontario assumed the management of GDB. The Human Genome Initiative is a worldwide research effort focusing on structural analysis of human DNA to determine the location and sequence of the estimated 100,000 human genes. In support of this project, GDB stores and curates data generated by researchers worldwide who are engaged in the mapping effort of the Human 25 Adapted from the National Library of Medicine: http://www.nlm.nih.gov/mesh/jablonski/about_syndrome.html. 26 Adapted from the Genome Database: http://gdbwww.gdb.org/gdb/aboutGDB.html - mission.
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Genome Project (HGP). GDB’s mission is to provide scientists with an encyclopedia of the human genome which is continually revised and updated to reflect the current state of scientific knowledge. Although GDB has historically focused on gene mapping, its focus will broaden as the Genome Project moves from mapping to sequence, and finally, to functional analysis.
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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 Down syndrome 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 Down syndrome. 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 Down syndrome. 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 “Down syndrome”:
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Guides on Down syndrome Down Syndrome http://www.nlm.nih.gov/medlineplus/downsyndrome.html
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Other guides Birth Defects http://www.nlm.nih.gov/medlineplus/birthdefects.html Bone Marrow Diseases http://www.nlm.nih.gov/medlineplus/bonemarrowdiseases.html Genetic Brain Disorders http://www.nlm.nih.gov/medlineplus/geneticbraindisorders.html Genetic Disorders http://www.nlm.nih.gov/medlineplus/geneticdisorders.html Genetic Testing/Counseling http://www.nlm.nih.gov/medlineplus/genetictestingcounseling.html Prader-Willi Syndrome http://www.nlm.nih.gov/medlineplus/praderwillisyndrome.html Turner's Syndrome http://www.nlm.nih.gov/medlineplus/turnerssyndrome.html
Within the health topic page dedicated to Down syndrome, the following was listed: •
General/Overviews Down Syndrome Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/professionals/681_1214.asp Down Syndrome Source: Nemours Foundation http://kidshealth.org/parent/medical/genetic/down_syndrome.html Questions and Answers about Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResGeneralArticle&article=194
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Specific Conditions/Aspects Alzheimer's Disease and Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResHlthArticle&article=33 Clinical Info: Endocrine Conditions in Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResHlthArticle&article=36 Clinical Info: The Heart and Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResHlthArticle&article=44
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Diseases of the Blood in Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResHlthArticle&article=201 Futures & Special Needs Planning for Persons with a Disability Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResLifePlanArticle&article=231 Is It Possible to Breastfeed My Baby Who Was Born with Down Syndrome? Source: La Leche League International http://www.lalecheleague.org/FAQ/down.html Sexuality in Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResHlthArticle&article=43 •
Children Clinical Info: Early Intervention and Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResHlthArticle&article=35 Coping with Disaster: Suggestions for Helping Children with Cognitive Disabilities Source: Administration for Children and Families http://www.acf.dhhs.gov/programs/add/Sept11/addcoping.html Down Syndrome Source: Nemours Foundation http://kidshealth.org/kid/health_problems/birth_defect/down_syndrome.html Speech And Language Skills In Infants, Toddlers and Young Children With Down Syndrome Source: National Down Syndrome Society http://www.ndss.org/content.cfm?fuseaction=InfoResDevArticle&article=216
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From the National Institutes of Health Facts about Down Syndrome Source: National Institute of Child Health and Human Development http://www.nichd.nih.gov/publications/pubs/downsyndrome/down.htm
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Latest News Early Screening May Help Detect Down Syndrome Source: 10/08/2003, Reuters Health http://www.nlm.nih.gov//www.nlm.nih.gov/medlineplus/news/fullstory_14221 .html
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Organizations March of Dimes Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/
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National Down Syndrome Society http://www.ndss.org/ National Institute of Child Health and Human Development http://www.nichd.nih.gov/ •
Prevention/Screening Prenatal Diagnosis: Amniocentesis and CVS Source: American Academy of Family Physicians http://familydoctor.org/handouts/144.html Prenatal Testing: What's Involved and Who Should Consider It Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=PR00014 Triple Screen Source: March of Dimes Birth Defects Foundation http://www.marchofdimes.com/pnhec/159_522.asp
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Research First Trimester Ultrasound Identifies More Cases of Down Syndrome Than Second Trimester Maternal Serum Screening and Is More Cost Effective Source: Agency for Healthcare Research and Quality http://www.ahrq.gov/research/may03/0503ra9.htm Same Old Story, Told by Individuals with Down Syndrome Source: American Speech-Language-Hearing Association http://www.asha.org/press/down_syndrome_narratives.cfm Treadmill Training May Help Children with Down Syndrome Walk Sooner Source: Nemours Foundation http://kidshealth.org/research/treadmill.html
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Statistics FASTATS: Birth Defects Source: National Center for Health Statistics http://www.cdc.gov/nchs/fastats/bdefects.htm
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Teenagers Young People with Down Syndrome: Transition from Childhood to Adulthood Source: National Down Syndrome Society http://www.ndss.org/ndss/main/content.cfm?fuseaction=InfoResLifePlanArticle &article=227
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.
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The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on Down syndrome. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Alzheimer's Disease and Down Syndrome Source: New York, NY: National Down Syndrome Society. 1995. 1 page, 6 panels. Contact: National Down Syndrome Society. 666 Broadway, New York, NY 10012-2317. (212) 460-9330; (800) 221-4602. PRICE: Free. Summary: Alzheimer's disease is far more common in people with Down syndrome than it is in the general population. However, not all people with Down syndrome will develop Alzheimer's disease, and even those showing Alzheimer's-type symptoms may not have Alzheimer's disease, since other conditions can mimic the symptoms. According to the author, it seemys reasonable to estimate that 25 percent or more of people with Down syndrome over age 35 show clinical signs and symptoms of Alzheimer's-type dementia, and the percentage increases with age. It is important to be sure that the symptoms do not result from other conditions, such as thyroid disease, depression, a brain tumor, recurrent strokes, metabolic imbalances, and various neurological conditions. The National Down Syndrome Society recommends that people with Down syndrome be tested at age 30 to provide a baseline reading for cognitive function. Periodic tests thereafter can show deterioration. Current research shows that the extra gene dosage caused by the abnormal third chromosome 21 of Down syndrome may have a causative relationship with Down syndrome.
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Alzheimer's Disease and Down Syndrome: The Connection Source: Rochester, NY: Alzheimer's Association, Rochester Chapter. 1993. [6 p.]. Contact: Alzheimer's Association, Rochester Chapter. 274 Goodman Street, Rochester, NY 14607. (800) 724-0587; (716) 442-3820. PRICE: $0.20, minimum order 50 copies; $15.00 charge to personalize with your organization's name. Summary: This brochure describes Alzheimer's disease, Down syndrome, and the connection between the two disorders. The brochure explains the symptoms and progression of Alzheimer's disease, the caregiving demands placed on family members, and the difficulty of making an accurate diagnosis. It also discusses the physical and mental effects of Down syndrome, the likelihood that older persons with Down syndrome will develop Alzheimer's disease, the similarities and differences between the brain changes seen in Down syndrome and those seen in Alzheimer's disease, the genetic link between the two disorders, and the effects of Alzheimer's disease on the person with Down syndrome and his or her caregivers. The brochure also explains how the Alzheimer's Association can help support persons who have this disease and their caregivers by offering monthly support group meetings where family members can share their concerns and receive practical advice from others in the same situation.
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Facts about Down Syndrome Source: Bethesda, MD: National Institute of Child Health and Human Development. 1997. 20 pp. Contact: Available from National Institute of Child Health and Human Development Clearinghouse, P.O. Box 3006, Rockville, MD 20847. Telephone: (800) 370-2943 TTY: (888) 320-6942 / fax: (301) 984-1473 / e-mail:
[email protected] / Web site: http://www.nichd.nih.gov/publications/info.htm. Available at no charge. Summary: This booklet for consumers describes the following aspects of Down Syndrome: the chromosomal basis; the possible factors in occurrence; prenatal testing and screening; diagnosis; associated medical disorders; Down Syndrome and newborns, infancy, preschool children, adolescents, and adults; areas of future research; and questions and answers. Additional organizational resources for information and assistance are included. The brochure is available in English and Spanish.
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Down syndrome: Guidelines for care for children with special health care needs Source: Minneapolis, MN: Services for Children with Handicaps, Minnesota Department of Health. 1992. 52 pp. Contact: Available from Minnesota Children with Special Health Care Needs, 717 Delaware Street, S.E., Box 9441, Minneapolis, MN 55440. Telephone: (612) 623-5150 or (800) 728-5420. Summary: This publication was developed for families and health professionals caring for children with Down syndrome. The guidelines are aimed at helping families coordinate the health care needed for the optimal growth and development of their child. General information concerning Down syndrome is provided along with an overview of the family centered health care team approach to treating a child or adolescent with this chromosome disorder. The publication also outlines the child's needs at various stages of her life in terms of health care, development, school, and child care. A glossary and list of resources are also included.
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National Association for Down Syndrome Source: Oak Brook, IL: National Association for Down Syndrome. 199x. 4 p. Contact: Available from National Association for Down Syndrome. P.O. Box 4542, Oak Brook, IL 60522-4542. (708) 325-9112. PRICE: Single copy free. Summary: The National Association for Down Syndrome (NADS) is a not-for-profit organization, formed in 1961 by parents of children with Down syndrome. This brochure outlines the purpose and activities of NADS. Topics covered include the goals of the organization, parent support, community parent groups, educational activities, seminars, the audio/visual programs and speakers bureau, the newsletter, research, and membership. The brochure includes a membership application form.
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ETC.: Effective Therapies Through Cued Speech. Articulation, Learning Disabilities, Phonics, Down Syndrome, Deaf-Blind, etc Source: Cleveland, OH: National Cued Speech Association. 1996. (Information Package). Contact: Available from Cued Speech Discovery. Bookstore of the National Cued Speech Association, 23970 Hermitage Road, Cleveland, OH 44122-4008. Voice/TTY (800) 459-
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3529 or (216) 292-6213; E-mail:
[email protected]. PRICE: $10.00 plus $3.00 shipping and handling. Summary: This information package contains a variety of information about cued speech and its use with children who have hearing impairments and a disability such as Down syndrome, learning disability, visual impairment, etc. The package is designed for the families of these children, and for professionals who work with them. It combines fact sheets, articles, and commentaries on cued speech. Topics include autism, pervasive developmental disorders, and cued speech; cued speech for children who are deaf-blind; cued speech and phonics; students who have reading difficulties and cued speech; the self-monitoring cue card (SMCC) format; cued speech for articulation therapy; cued speech for persons who have mental retardation; and the views of speechlanguage pathologists on cued speech. The information packet also lists recommended readings and resources for additional materials. •
Down Syndrome and Alzheimer Disease Source: Toronto, Ontario: Alzheimer Society of Canada. April 1995. [2 p.]. Contact: Alzheimer Society of Canada. 1320 Yonge Street, Suite 201, Toronto, Ontario M4T 1X2, CANADA. (416) 925-3552. PRICE: Free. Summary: This fact sheet explains what Down syndrome (DS) is, how it is associated with Alzheimer's disease (AD), what considerations exist for making a diagnosis of AD when DS is involved, and whether there are differences in caring for a patient with AD and DS as opposed to someone with AD. The sheet explains that in patients with DS, the prevalence of AD increases with age, as it does with the general population. It suggests that making a diagnosis of AD is more difficult in people with DS because of the similarities in symptoms, the inability of the assessment process to adequately distinguish between the two diseases, and the limited communication skills of patients with DS. Physicians may rely on caregivers for a detailed medical history to separate AD symptoms from pre-existing disabilities. While there are no real differences in care for patients with both DS and AD, certain considerations may need to be addressed when AD symptoms become more apparent, such as the need for additional caregiver support and education. Also available in French. (See: AZDC05407).
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Down Syndrome Source: in DeFeo, A.B., ed. Parent Articles 2. San Antonio, TX: Communication Skill Builders. 1995. p. 125-127. Contact: Available from Communication Skill Builders. Customer Service, 555 Academic Court, San Antonio, TX 78204-2498. (800) 211-8378; Fax (800) 232-1223. PRICE: $55.00 plus shipping and handling. Order Number 076-163-0732. Summary: This fact sheet, from a communication skills book for parents, provides information on Down syndrome. Topics covered include a description of Down syndrome, speech and language skills in children with Down syndrome, and the importance of early speech language therapy in this population. The author provides detailed suggestions for parent-child interaction, including recommended activities and language to use in conversation. The author encourages parents to incorporate these suggestions into everyday routines. The fact sheet concludes with a list of related vocabulary and a brief list of resources. 4 references.
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Health Care Management of Adults with Down Syndrome Source: American Family Physician. 64(6): 1031-1038. September 15, 2001. Contact: Available from American Academy of Family Physicians. Publications Division, 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 944-0000. Website: www.aafp.org/afp. Summary: The family physician's holistic approach to patients forms the basis of good health care for adults with Down syndrome. This article reviews the health care management of adults with Down syndrome, including the need for adequate oral health care. Patients with Down syndrome are likely to have a variety of illnesses, including thyroid disease, diabetes, depression, obsessive-compulsive disorder, hearing loss, atlantoaxial subluxation, and Alzheimer disease. In addition to routine health screening, patients with Down syndrome should be screened for sleep apnea, hypothyroidism, signs and symptoms of spinal cord compression, and dementia. Patients with Down syndrome may have an unusual presentation of an ordinary illness or condition, and behavior changes or a loss of function may be the only indication of medical illnesses. Plans for long term living arrangements, estate planning, and custody arrangements should be discussed with the parents or guardians. Because of improvements in health care and better education, and because more people with this condition are being raised at home, most adults with Down syndrome can expect to function well enough to live in a group home and hold a meaningful job. A patient information handout on health issues in adults with Down syndrome accompanies the article. 1 figure. 2 tables. 37 references.
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Primary Care of Infants and Young Children with Down Syndrome Source: American Family Physician. 59(2): 381-396. January 15, 1999. Contact: Available from American Academy of Family Physicians. Publications Division, 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672. (800) 944-0000. Website: www.aafp.org/afp. Summary: Down syndrome is caused by triplicate material of chromosome 21. The syndrome has a variable physical expression, but congenital cardiac (heart) defects, transient myelodysplasias (defective development of the spinal cord) of the newborn, and duodenal atresia (closure or blockage of the duodenum, the opening between stomach and small intestine) are highly specific for this chromosomal disorder. Routine health maintenance is important because infants and children with Down syndrome are more likely to have otitis media (middle ear infection), thyroid disease, congenital cataracts, leukemoid reactions, dental problems, and feeding difficulties. This article helps primary care physicians understand the varied aspects of treating infants and young children with Down syndrome. The author notes that since infants with this syndrome are prone to respiratory infections, immunization recommendations should be followed closely. Motor, language, social, and adaptive skills should be assessed at each office visit. The psychosocial aspects of care should be discussed with the parents of an infant with Down syndrome. If necessary, the parents should be referred to family support and specialty resources. With newer surgical techniques, early therapy to minimize developmental delay, and proper health supervision, the functional prognosis for infants with Down syndrome is considerably improved. 7 tables. 39 references.
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Trisomy 21-Down Syndrome Source: Kansas City, MO: University of Missouri, School of Dentistry. 1990. 1 p.
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Contact: Available from University of Missouri, Kansas City. School of Dentistry, 650 East 25th Street, Kansas City, MO 64108. (816) 235-2111; http://www.umkc.edu/dentistry. PRICE: Single copy free. Summary: This fact sheet, part of a series on oral health and various disabling conditions, discusses trisomy 21-Down Syndrome. The authors note that although a unique set of dental conditions associated with this syndrome, the risk of dental diseases is related to the client's age, degree of mental disability, home environment, and ability to perform daily oral care. Topics covered include common dental problems associated with developmental changes in the teeth; common dental problems associated with poor or incomplete oral hygiene and/or infrequent professional cleanings; clients with heart defects and possible prophylactic use of antibiotics; other conditions, including pica, tongue thrusting habit, clenching and bruxing teeth, drooling, and self-injurious behaviors; and preventive management concerns and strategies. The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “Down syndrome” (or synonyms). The following was recently posted: •
Health supervision for children with Down syndrome Source: American Academy of Pediatrics - Medical Specialty Society; 2001 February; 8 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2778&nbr=2004&a mp;string=Down+AND+syndrome 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: •
Down Syndrome Fact Sheet Source: NOAH: New York Online Access to Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=3264
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Down Syndrome Information for Parents and Professionals Summary: There is information on this site for both professionals and consumers. Source: National Down Syndrome Society http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=2575
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The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Down syndrome. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. PEDBASE Similar to NORD, PEDBASE covers relatively rare disorders, limited mainly to pediatric conditions. PEDBASE was designed by Dr. Alan Gandy. To access the database, which is more oriented to researchers than patients, you can view the current list of health topics covered at the following Web site: http://www.icondata.com/health/pedbase/pedlynx.htm. Additional Web Sources
A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Associations and Down Syndrome The following is a list of associations that provide information on and resources relating to Down syndrome: •
Association for Children with Down Syndrome, Inc Telephone: (516) 933-4700 Fax: (516) 933-9524 Email:
[email protected] Web Site: http://www.acds.org Background: The Association for Children with Down Syndrome, Inc. (ACDS) is an international not-for-profit voluntary organization dedicated to providing information
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and support to individuals affected by Down Syndrome, their families, and health care professionals. Down Syndrome is a congenital disorder resulting from abnormalities affecting chromosome 21. Established in 1966, the Association for Children with Down Syndrome offers a wide variety of programs and services. Its 5 Plus Program provides recreational and social services for individuals with Down Syndrome from five years of age through adulthood and for their families. In addition, the ACDS's association with the Child Development Center/Genetics Program at North Shore University HospitalCornell University Medical College helps make many essential services available to ACDS families, such as pediatric cardiology, psychology, and gastroenterology services. The ACDS also promotes research, provides families with home and hospital visitations, and has a trained parent counselor. Additional programs and services include parent advocacy training and assistance; regular conferences and workshops for parents and professionals; and a special library that offers up-to-date toys, books, and videos. The Association offers brochures, articles, manuals, bibliographies of resources on certain topics (e.g., genetics, legal issues, mental health, recreation, employment, etc.), and a regular newsletter. Relevant area(s) of interest: Down Syndrome •
Birth Defect Research for Children, Inc Telephone: (407) 895-0802 Fax: (407) 895-0824 Email:
[email protected] Web Site: http://www.birthdefects.org Background: Birth Defect Research for Children, Inc., (BDRC) formerly the Association of Birth Defect Children gives parents and expectant parents information about specific birth defects, their causes and treatments, support group referrals and parent-matching services. BDRC also provides information about environmental exposures that may be associated with birth defects. To study these exposures further, BDRC sponsors the National Birth Defect Registry, a research project designed to collect data on all kinds of birth defects and prenatal/preconceptual exposures of mothers and fathers. Relevant area(s) of interest: Down Syndrome
•
Canadian Down Syndrome Society Telephone: (403) 270-8500 Toll-free: (800) 883-5608 Fax: (403) 270-8291 Email:
[email protected] Web Site: http://home.ican.net/~cdss Background: The Canadian Down Syndrome Society (CDSS) is a nonprofit support organization dedicated to enhancing the quality of life for all individuals who have Down syndrome. Down Syndrome is the most common and readily identifiable genetic condition associated with mental retardation. Some common characteristics of Down Syndrome include an usually small head (microcephaly); a small mouth; a flat nasal bridge; white (Brushfield) spots in the iris of the eyes; a downward slant to the eyes with a fold of skin on the inner corners (epicanthal folds); small ears that may be folded over at the top; a short neck; a transverse (Simian) crease on the palm of the hands; and poor muscle tone (hypotonia). All children with Down Syndrome have some degree of mental retardation. Generally mental retardation is in the mild to moderate range, but
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sometimes it can be profound. Established in 1987, CDSS works to fulfill its goals to act as a support group for individuals with Down syndrome, their parents, and families; to demystify Down syndrome by increasing societal awareness about the value, rights, and individual capabilities of people with Down syndrome; to build and maintain a national communication network accessible to all those with an interest in Down syndrome; to promote, encourage, and support research that has the potential to enhance the quality of life of people with Down syndrome; to develop support services and projects that enhance quality of life for individuals with Down syndrome; to provide an opportunity for individuals with Down syndrome to express their views, and participate in the direction of society; and to provide a forum for the exchange of information between individuals with Down syndrome, parents, and professionals. The Society publishes a newsletter entitled 'CDSS Quarterly' and an educational brochure series in both English and French with titles that include 'Your Baby: Information About Down Syndrome,' 'Preventative Medical Guidelines for Children With Down Syndrome,' and 'Sexuality, Relationships and Adolescents With Down Syndrome.'. •
Cardiac Arrhythmias Research and Education Foundation, Inc Telephone: (949) 752-2273 Toll-free: (800) 404-9500 Fax: (949) 752-9119 Email:
[email protected] Web Site: http://www.longqt.org/ Background: The Cardiac Arrhythmias Research and Education Foundation, Inc. (CARE Foundation) is a national not-for-profit organization dedicated to promoting physician education and public awareness of the unexpected sudden death of children and young adults due to heart rhythm disorders. Cardiac arrhythmias are disturbances in the heart s natural rhythm. These disturbances are caused by disruptions in the normal conduction of electrical signals within the heart. Due to various reasons, electrical signals may be detoured, slowed, or blocked while traveling through certain parts of the heart. This may cause the heart s natural rhythm to speed up, slow down, or become irregular, affecting the flow of blood to the body s internal organs. The CARE Foundation was founded in 1995 by a group of electrophysiologists and individuals who have been affected by sudden cardiac death. The Foundation s primary goals are to raise funds for clinical research of cardiac arrhythmias and to educate the public and the medical community about the prevention and treatment of arrhythmias. The Foundation promotes screening for at-risk families and participation in ongoing genetic research studies. Foundation activities include providing physician referrals and conducting informational meetings and national seminars for affected families and physicians throughout the country. Publications produced by the CARE Foundation include brochures on various types of cardiac arrhythmias such as right ventricular dysplasia, mitral valve prolapse, hypertrophic cardiomyopathy, neurocardiogenic syncope, atrial fibrillation, and paroxysmal supraventricular tachycardia. The organization also publishes a regular newsletter entitled 'CARE'.
•
Center for Mental Retardation Telephone: (216) 621-5858 Toll-free: (800) 899-3039 Fax: (216) 621-0221 Email:
[email protected] Web Site: None
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Background: The Center for Mental Retardation (Edward I. and Fannie L. Baker International Resource Center for Down Syndrome) is a not-for-profit organization dedicated to improving the quality of life for individuals with mental retardation and increasing their role as valued, contributing members of society through the implementation and promotion of services, educational programs, and research. Down Syndrome is a congenital chromosomal disorder characterized by varying degrees of mental retardation, characteristic abnormalities of the head and facial area, malformations of the hands and/or feet, congenital heart defects in approximately 25 percent of affected individuals, and/or other abnormalities. In most individuals with Down Syndrome, all or a portion of chromosome 21 appears three times rather than twice in cells of the body; however, in rare cases, the disorder may occur due to a chromosomal translocation involving chromosome 21 and another chromosome. Established in 1963, the Center for Mental Retardation offers a variety of services and programs including patient advocacy services, parent counseling and support, referral services, and patient and professional education. The Center's educational materials include brochures, pamphlets, and a regular newsletter. Relevant area(s) of interest: Down Syndrome, Trisomy G Syndrome •
Children's Neurobiological Solutions Foundation Telephone: (805) 965-8838 Fax: (805) 963-6633 Email:
[email protected] Web Site: http://www.cnsfoundation.org Background: Children's Neurobiological Solutions Foundation is a national, non-profit, 501(c)(3) organization whose mission is to orchestrate cutting-edge, collaborative research with the goal of expediting the creation of effective treatments and therapies for children with neurodevelopmental abnormalities, birth injuries to the nervous system, and related neurological problems. In addition, CNS strives to provide families and health care providers with user-friendly access to information and education supporting their decision-making process. Relevant area(s) of interest: Down Syndrome
•
Down's Syndrome Association (UK) Telephone: 0181 682 4001 Fax: 0181 682 4012 Email:
[email protected] Web Site: http://www.downs-syndrome.org.uk/ Background: The Down's Syndrome Association (UK) is an international voluntary organization in the United Kingdom dedicated to supporting parents and other caregivers of individuals with Down's syndrome and improving the lives of those with the disorder. Down's syndrome is a chromosomal disorder in which all or a portion of chromosome 21 appears three times (trisomy) rather than twice in some (mosaicism) or all of the cells of the body. Although associated symptoms and findings may vary from case to case, many affected infants have abnormally diminished muscle tone (hypotonia); short, broad hands and feet; and characteristic abnormalities of the head and facial (craniofacial) area, including an unusually small, short head (microbrachycephaly), a flattened back portion of the head (occiput), low-set ears, a
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depressed nasal bridge, and a large, protruding tongue. Individuals with Down's syndrome may also have chronic respiratory infections, heart defects that are present at birth (congenital heart defects), and other physical malformations. Although the level of mental retardation may vary from case to case, most affected individuals have mild mental retardation. The Down's Syndrome Association includes several branches that welcome and support new members, provide access to a range of resources, arrange social and fundraising events, produce newsletters, and contribute to the development of the Association through representation at its National Forum. In addition, the Association produces and distributes its own regular newsletter and sponsors conferences and other events throughout the year. The Down's Syndrome Association (UK) also offers several additional programs and services. For example, its information service provides literature on Down's syndrome and responds to inquiries relating to all aspects of the disorder including prenatal screening and diagnosis, education, health care, behavioral difficulties, respite care, holidays, and other areas. In addition, the organization's welfare benefits advisor provides information and advice on all aspects of the welfare system, offers information sheets on various benefits, and provides additional services, including representing affected families at appeal tribunals. •
Foundation for Blood Research Telephone: (207) 883-4131 Toll-free: (800) 639-8605 Fax: (207) 885-0807 Email:
[email protected] Web Site: http://www.fbr.org Background: The Foundation for Blood Research (FBR) is a nonprofit medical research and education institute consisting of biostatistical, laboratory, public health, and education experts. Established in 1977, the Foundation is committed to determining more effective ways to identify, manage, and prevent human disease through clinical and laboratory investigation, the study of disease incidence and prevalence (epidemiology), scientific educational outreach programs, computer-based analyses, public health program design, and clinical testing. The Foundation for Blood Research's mission is to develop and improve laboratory tests as a way to help physicians identify, treat, manage, and, when possible, prevent illness. The Foundation's scientific activities, which primarily involve genetics and immunology, focus on two main areas of preventive medicine: the development of medical screening systems to identify certain disease conditions found in the general population and the application of certain tests (i.e., measurement of specific proteins in the liquid portion of the blood [serum]) to detect or predict particular disorders. The Foundation is also committed to expanding scientific knowledge and awareness among health professionals, science students at all levels, and the general public. The Foundation for Blood Research provides a variety of educational materials for professionals and the lay public including a regular newsletter; reports; medical books including 'Serum Proteins in Clinical Medicine-Volume I: Laboratory Section'; medical handbooks such as 'Prenatal Screening for Major Fetal Disorders-Volume II: Down Syndrome'; an interactive module entitled 'Chances' Choices,' which was designed for teaching human genetics to high school biology students; and educational pamphlets. Such pamphlets include 'Understanding Ventral Wall Defects,' which discusses birth defects characterized by an abnormal opening in an affected infant's abdominal (ventral) wall, and 'Understanding Anencephaly,' which describes a rare birth defect characterized by absence of many of the structures of the skull, brain, and spinal cord. FBR's Southern Maine Genetics Services Program (SMGS)
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constitutes half of Maine's State Genetics Program. It provides genetics services regardless of ability to pay to individuals, families and couples in southern and southeastern/western Maine. This program is involved in a pilot project for bringing genetics services to rural populations via interactive television or telemedicine at 23 participating sites from Fort Kent at the northern tip of Maine to Bath in the mid-coast of Maine. These services are both clinical and educational, with CME or CEU educational offerings for practitioners available on request. SMGS is author and producer of 'A Practice-Based Genetics Curriculum for Nurse Educators,' a modular educational program designed to support integration of genetics into nursing curricula and continuing education. Another SMGS educational tool is 'The Genetics Resource Guide,' a compact manual covering prenatal, family history and adult-onset genetic conditions; free to all Maine community, visiting and public health nurses. •
International Mosaic Down Syndrome Association Telephone: (979) 828-1868 Fax: (775) 295-9373 Email:
[email protected] Web Site: www.imdsa.com Background: The International Mosaic Down Syndrome Association (IMDSA) is a nonprofit organization that is designed to assist any individual whose life has been affected by Mosaic Down syndrome. IMDSA provides information and support, assists in research, and strives to increase awareness in medical, educational, and public communities throughout the world. Because of the rarity of Mosaic Down syndrome, the organization is mostly Internet-based. It does have Country Representatives in place in many countries to contact new parents of children with MDS. Its website, www.imdsa.com, offers an online translator through Babelfish.
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MAGIC Foundation for Children's Growth Telephone: (708) 383-0808 Toll-free: (800) 362-4423 Fax: (708) 383-0899 Email:
[email protected] Web Site: http://www.magicfoundation.org Background: The MAGIC Foundation is a national non-profit organization dedicated to helping children and adults with growth related disorders. Established in 1989, it provides services that include public education and awareness, quarterly newsletters, national networking, an annual convention, disease specific brochures, and a Kids Program. Its current divisions include Growth Hormone Deficiency, Russell Silver Syndrome, McCune Albright Syndrome, Congenital Adrenal Hyperplasia, Precocious Puberty, Turner Syndrome, Septo Optic Dysplasia, Panhypopituitarism, Adult Growth Hormone Deficiency, Genital and Reproductive Anomalies in Children and Rare Disorders. Educational materials produced by the foundation include general brochures, a networking form, disease specific brochures, and a video entitled Just Say Yes to Growth Hormone.
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March of Dimes Birth Defects Foundation Telephone: (914) 428-7100 Toll-free: (888) 663-4637
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Fax: (914) 997-4763 Email:
[email protected] Web Site: http://www.marchofdimes.com Background: The March of Dimes Birth Defects Foundation is a national not-for-profit organization that was established in 1938. The mission of the Foundation is to improve the health of babies by preventing birth defects and infant mortality. The March of Dimes funds programs of research, community services, education, and advocacy. Educational programs that seek to prevent birth defects are important to the Foundation and to that end it also produces a wide variety of printed informational materials and videos. The Pregnancy and Newborn Health Education Center staffs trained health information specialists who provide researched information on pregnancy issues, complications and risks, newborn care, birth defects, genetic diseases and related topics as well as referrals to relevant organizations and support groups. Relevant area(s) of interest: Down Syndrome •
National Down Syndrome Congress Telephone: (770) 604-9500 Toll-free: (800) 232-6372 Fax: (770) 604-9898 Email:
[email protected] Web Site: www.ndsccenter.org Background: The National Down Syndrome Congress (NDSC), a not-for-profit organization established in 1971, is committed to building a sense of community among all those concerned with Down syndrome. The Congress provides leadership in the formation of public policy and encourages ethically responsible research in all aspects of Down syndrome. The organization seeks to educate professionals, parents, and the community about Down syndrome and fosters self-advocacy, rights, and full participation in all aspects of community life. The National Down Syndrome Congress is also dedicated to developing position statements on major issues; providing a network that links state and local groups and affiliates; and enhancing relationships within the organizations communities and the broader disability community. The National Down Syndrome Congress provides a telephone hotline offering information on any subject related to Down syndrome. It conducts an annual convention, provides appropriate referrals, and coordinators a local parent group network and maintains directory of such groups to promote parent-to-parent and parent-to-professional networking. The National Down Syndrome Congress provides a variety of educational and support materials through its regular journal 'Down Syndrome News,' reports, brochures, and bibliographies of relevant materials. Relevant area(s) of interest: Down Syndrome, Trisomy G Syndrome
•
National Down Syndrome Society Telephone: (212) 460-9330 Toll-free: (800) 221-4602 Fax: (212) 979-2873 Email:
[email protected] Web Site: http://www.ndss.org/ Background: The National Down Syndrome Society is a national voluntary not-forprofit organization dedicated to providing support to people affected by Down
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Syndrome and increasing public awareness. The National Down Syndrome Society s goals are to promote better understanding of Down Syndrome and help affected individuals reach their personal potential; support research about this genetic disorder; and disseminate accurate and up-to-date information on Down Syndrome to parents, professionals, and other interested individuals. Established in 1979, the Society also supports several pilot demonstration programs to address specific areas of concern among families affected by Down Syndrome. It confers scholar awards and two-year grants to promising young scientific students and conducts a biannual research symposium. The Society also provides referrals to medical professionals and support groups and holds conferences to update research advances. The National Down Syndrome Society has an extensive supply of educational and support materials including a series of fact sheets, a bibliography of reading materials, brochures, pamphlets, booklets, fliers, and videos. A magazine entitled 'News N Views' and a quarterly newsletter entitled 'The National Down Syndrome Society Update' are also available from the Society. Relevant area(s) of interest: Down Syndrome, Trisomy G Syndrome •
New Directions for People with Disabilities, Inc Telephone: (805) 967-2841 Toll-free: (888) 967-2841 Fax: (805) 964-7344 Email:
[email protected] Web Site: NewDirectionsTravel.com Background: New Directions for People with Disabilities, Inc., a not-for-profit organization established in 1985, is dedicated to providing local, national, and international travel and foreign exchange programs for people with disabilities. The purpose of the programs is to promote the understanding, acceptance, and appreciation of people with disabilities as important and contributing members of our society as well as to promote a sense of accomplishment, belonging, and self-worth for participants by providing a wide range of challenging activities. Such activities include skiing, river rafting, biking tours, and hot air ballooning. The Tour Guides/Chaperones are special educational instructors, recreation therapists, residential counselors, nurses, nurses aides, vocational and independent living skill counselors, and other professional staff who have been trained to work with people with disabilities. Each year, New Directions serves over 350 children, adults, and seniors who have developmental, emotional, and physical disabilities such as cerebral palsy, Down Syndrome, autism, schizophrenia, blindness, hearing impairment, and mental retardation. Participants live in state hospitals, board and care homes, residential treatment centers, and nursing homes. Most have not previously had a vacation, and many have not been away from their facilities or treatment centers for 10 or more years. New Directions annually sponsors trips in the United States and abroad to locations including Hawaii, Washington D.C., New York City, Las Vegas, Disneyland, the Grand Canyon, Australia, Ireland, Japan, and Mexico. Relevant area(s) of interest: Down Syndrome
•
Roeher Institute Telephone: (416) 661-9611 Toll-free: (800) 856-2207 Fax: (416) 661-5701 Email:
[email protected]
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Web Site: http://www.roeher.ca Background: The Roeher Institute, located in Ontario, Canada, is a nonprofit organization dedicated to the study of public policy affecting people with intellectual impairments and other disabilities. Established in 1957, the Institute has an extensive national and international network and acts as a clearinghouse for information about disability issues around the world. The Institute s services include reference and referral information; customized responses to information requests; a generation of bibliographies on specific topics; and the development of customized information packages. The Roeher Institute s goals are to examine and understand issues that affect individuals with an intellectual impairment and other disabilities; to act as a center for the exchange of ideas and to encourage new ways of thinking about persons with an intellectual impairment and other disabilities; and to provide insight into the social policy, programs, laws, and other features of Canadian society that affect the capacity of people with an intellectual impairment and other disabilities to exercise their rights and fully participate in society. Educational materials include a pamphlet entitled 'An International Information Centre of Disability at The Roeher Institute,' a catalog that lists resource books, and a booklet entitled 'Issues and Resources.' The Institute supports research, encourages educational activities, and provides appropriate referrals. Relevant area(s) of interest: Down Syndrome •
Society for Mucopolysaccharide (MPS) Diseases Telephone: (149) 443-4156 Fax: (149) 443-4252 Email:
[email protected] Web Site: http://www.vois.org.uk/mps Background: The Society for Mucopolysaccharide (MPS) Diseases is a voluntary international organization in the United Kingdom dedicated to providing information, support, and advocacy services to individuals affected by mucopolysaccharide and related diseases and their family members. The Society was founded in 1982 by a group of parents with children affected by MPS disorders and currently consists of approximately 1,000 members and 12 regional family support networks. The mucopolysaccharide diseases (mucopolysaccharidoses) belong to a group of rare metabolic disorders known as lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that break down certain fats and carbohydrates. The mucopolysaccharidoses are characterized by an abnormal accumulation of certain fatty substances (mucolipids) and/or complex carbohydrates (mucopolysaccharides) within cells of particular tissues of the body. The different forms of MPS disease, such as Hurler syndrome (MPS I), Hunter syndrome (MPS II), etc., are often characterized by multiple abnormalities of the skull and face, growth delays, mental retardation, and/or, depending upon the specific form of MPS, additional symptoms and findings that may vary in range and severity. In many of the mucopolysaccharidoses, life-threatening complications may result during childhood. The Society for Mucopolysaccharide Diseases is committed to promoting and supporting research to further the understanding and improve the treatment of MPS disorders, offering networking services to affected families, and providing practical assistance in areas of health, welfare, education, adaptations, and respite care. In addition, the Society provides referrals to help affected children receive appropriate specialist care and treatment, has a 24-hour help line, holds an annual conference where affected families and medical professionals may share knowledge, and conducts family holidays and adventure
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holidays where families may get to know one another in a relaxing, supportive atmosphere. The Society also has a web site on the Internet and provides a variety of educational materials including brochures, booklets, and a regular newsletter. •
The Arc (a national organization on mental retardation) Telephone: (301) 565-3842 Toll-free: (800) 433-5255 Fax: (301) 565-3843 Email:
[email protected] Web Site: http://thearc.org/ Background: The Arc is the largest organization in the United States that is solely devoted to improving the lives of all children and adults with mental retardation. The organization offers support to families affected by mental retardation and fosters research and educational programs on the prevention of mental retardation. The Arc is committed to securing opportunities for all people with mental retardation. To this end, the organization emphasizes personal opportunities for choice in education, housing, employment, and entertainment. The Arc is further committed to reducing the incidence and limiting the consequences of mental retardation through research, advocacy, and mutual support. The Arc provides leadership in the field of mental retardation and develops necessary human and financial resources to attain its goals. In addition, the Arc provides a wide variety of educational materials for parents, teachers, health care professionals, and others, including a regular newsletter, handbooks, instruction packets, reports, booklets, audio-visual aids, posters, and brochures. Many materials are available in Spanish. Relevant area(s) of interest: Down Syndrome
•
Tracheo Oesophageal Fistula Support Group (TOFS) Telephone: 0115 961 3092 Fax: 0115 961 3097 Email:
[email protected] Web Site: www.tofs.org.uk Background: The Tracheo Oesophageal Fistula Support Group (TOFS) is an international voluntary organization dedicated to providing information and support to parents who have a child born with tracheo-esophogeal fistula (TOF). In TOF, a section of the baby s throat is abnormally joined to the windpipe (esophagus) making it difficult for food and saliva to pass into the stomach. Established in 1982, TOFS consists of an 800 plus family membership and a national network of volunteers, all of whom are parents of children with TOF. The Support Group receives calls from affected families and professionals; maintains contact with sister organizations in other countries; and maintains a databank of information on matters such as feeding problems, tube feeding, and financial assistance. A video has been produced that explains the condition and the problems affecting children with TOF. In addition, TOFS raises funds to support its own work, to purchase equipment for hospitals and individuals, and to finance research. Support groups for affected individuals, family members, and healthcare professionals are provided along with educational materials. In addition to educational materials, audiovisual aides entitled, 'Your Life In Their Hands,' 'History of TOF,' and 'Reach,' along with many others are available. A national conference for members and professionals is organized every two years. A quarterly newsletter entitled, 'Chew' is
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also available. Fund-raising is undertaken to assist hospitals to purchase specialized equipment. Relevant area(s) of interest: Down Syndrome
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Down syndrome. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Down syndrome. 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 Down syndrome. 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 “Down syndrome” (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 “Down syndrome”. 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 “Down syndrome” (or synonyms) into the “For
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these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Down syndrome” (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.27
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
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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)28: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
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Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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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
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
320 Down Syndrome
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
321
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
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Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
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 Down syndrome: •
Basic Guidelines for Down Syndrome ALL Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000541.htm Down syndrome Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000997.htm
•
Signs & Symptoms for Down Syndrome Decreased muscle tone Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm Epicanthal folds Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003030.htm Hearing loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003044.htm
322 Down Syndrome
Microcephaly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003272.htm Retarded growth and development Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003021.htm Single palmar crease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003290.htm Sutures - separated Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003307.htm Tongue problems Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003047.htm Upward slant Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003316.htm Vision problems Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Visual problems Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003029.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm •
Diagnostics and Tests for Down Syndrome Amniocentesis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003921.htm CBC Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003642.htm Chromosome studies Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003935.htm ECG Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003868.htm Echocardiogram Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003869.htm Ultrasound Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003336.htm X-ray Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003337.htm
Online Glossaries 323
•
Background Topics for Down Syndrome Auscultation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002226.htm Cardiovascular Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002310.htm Duodenum Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002347.htm Heart disease Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000147.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Iris Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002386.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm Prenatal diagnosis Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002053.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
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
325
DOWN SYNDROME DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdomen: That portion of the body that lies between the thorax and the pelvis. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Abscess: Accumulation of purulent material in tissues, organs, or circumscribed spaces, usually associated with signs of infection. [NIH] Acatalasia: A rare autosomal recessive disorder resulting from the absence of catalase activity. Though usually asymptomatic, a syndrome of oral ulcerations and gangrene may be present. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] 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] Acidemia: Increased acidity of blood. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Actin: Essential component of the cell skeleton. [NIH] Acuity: Clarity or clearness, especially of the vision. [EU] Acute leukemia: A rapidly progressing cancer of the blood-forming tissue (bone marrow). [NIH]
Acute lymphoblastic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphocytic leukemia. [NIH] Acute lymphocytic leukemia: ALL. A quickly progressing disease in which too many immature white blood cells called lymphoblasts are found in the blood and bone marrow. Also called acute lymphoblastic leukemia. [NIH] Acute myelogenous leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute nonlymphocytic leukemia. [NIH] Acute myeloid leukemia: AML. A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute
326 Down Syndrome
myelogenous leukemia or acute nonlymphocytic leukemia. [NIH] Acute nonlymphocytic leukemia: A quickly progressing disease in which too many immature blood-forming cells are found in the blood and bone marrow. Also called acute myeloid leukemia or acute myelogenous leukemia. [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] Adipocytes: Fat-storing cells found mostly in the abdominal cavity and subcutaneous tissue. Fat is usually stored in the form of tryglycerides. [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] Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aetiology: Study of the causes of disease. [EU] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU]
Dictionary 327
Affinity Chromatography: In affinity chromatography, a ligand attached to a column binds specifically to the molecule to be purified. [NIH] AFP: Alpha-fetoprotein. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]
Age Distribution: The frequency of different ages or age groups in a given population. The distribution may refer to either how many or what proportion of the group. The population is usually patients with a specific disease but the concept is not restricted to humans and is not restricted to medicine. [NIH] Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from aging, a physiological process, and time factors which refers only to the passage of time. [NIH] Age Groups: Persons classified by age from birth (infant, newborn) to octogenarians and older (aged, 80 and over). [NIH] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agenesis: Lack of complete or normal development; congenital absence of an organ or part. [NIH]
Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Airway Obstruction: Any hindrance to the passage of air into and out of the lungs. [NIH] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Aldehyde Dehydrogenase: An enzyme that oxidizes an aldehyde in the presence of NAD+ and water to an acid and NADH. EC 1.2.1.3. Before 1978, it was classified as EC 1.1.1.70. [NIH]
Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU]
328 Down Syndrome
Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1. [NIH] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allogeneic: Taken from different individuals of the same species. [NIH] Allogeneic bone marrow transplantation: A procedure in which a person receives stem cells, the cells from which all blood cells develop, from a compatible, though not genetically identical, donor. [NIH] Alopecia: Absence of hair from areas where it is normally present. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alpha-fetoprotein: AFP. A protein normally produced by a developing fetus. AFP levels are usually undetectable in the blood of healthy nonpregnant adults. An elevated level of AFP suggests the presence of either a primary liver cancer or germ cell tumor. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Alternative Splicing: A process whereby multiple protein isoforms are generated from a single gene. Alternative splicing involves the splicing together of nonconsecutive exons during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form messenger RNA. The alternative forms produce proteins in which one part is common while the other part is different. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ameliorating: A changeable condition which prevents the consequence of a failure or accident from becoming as bad as it otherwise would. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH]
Dictionary 329
Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amniocentesis: Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. [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] Amplification: The production of additional copies of a chromosomal DNA sequence, found as either intrachromosomal or extrachromosomal DNA. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloidosis: A group of diseases in which protein is deposited in specific organs (localized amyloidosis) or throughout the body (systemic amyloidosis). Amyloidosis may be either primary (with no known cause) or secondary (caused by another disease, including some types of cancer). Generally, primary amyloidosis affects the nerves, skin, tongue, joints, heart, and liver; secondary amyloidosis often affects the spleen, kidneys, liver, and adrenal glands. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Analysis of Variance: A statistical technique that isolates and assesses the contributions of categorical independent variables to variation in the mean of a continuous dependent variable. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphase: The third phase of cell division, in which the chromatids separate and migrate to opposite poles of the spindle. [NIH] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH]
330 Down Syndrome
Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Aneuploidy: The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of chromosomes or chromosome pairs. In a normally diploid cell the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is monosomy (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is trisomy (symbol: 2N+1). [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [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] Angiogenesis inhibitor: A substance that may prevent the formation of blood vessels. In anticancer therapy, an angiogenesis inhibitor prevents the growth of blood vessels from surrounding tissue to a solid tumor. [NIH] Angiopathy: Disease of the blood vessels (arteries, veins, and capillaries) that occurs when someone has diabetes for a long time. There are two types of angiopathy: macroangiopathy and microangiopathy. In macroangiopathy, fat and blood clots build up in the large blood vessels, stick to the vessel walls, and block the flow of blood. In microangiopathy, the walls of the smaller blood vessels become so thick and weak that they bleed, leak protein, and slow the flow of blood through the body. Then the cells, for example, the ones in the center of the eye, do not get enough blood and may be damaged. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] 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]
Annexins: Family of calcium- and phospholipid-binding proteins which are structurally related and exhibit immunological cross-reactivity. Each member contains four homologous 70 kD repeats. The annexins are differentially distributed in vertebrate tissues (and lower eukaryotes) and appear to be involved in membrane fusion and signal transduction. [NIH] Anomalies: Birth defects; abnormalities. [NIH] Anterior chamber: The space in front of the iris and behind the cornea. [NIH] Anthracycline: A member of a family of anticancer drugs that are also antibiotics. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of
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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] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] 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] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Apraxia: Loss of ability to perform purposeful movements, in the absence of paralysis or sensory disturbance, caused by lesions in the cortex. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal
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phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [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] Arteriovenous: Both arterial and venous; pertaining to or affecting an artery and a vein. [EU] Articulation: The relationship of two bodies by means of a moveable joint. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Aspiration: The act of inhaling. [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] Atopic: Pertaining to an atopen or to atopy; allergic. [EU] Atresia: Lack of a normal opening from the esophagus, intestines, or anus. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU]
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Audiologist: Study of hearing including treatment of persons with hearing defects. [NIH] Audition: The sense of hearing. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Auditory Cortex: Area of the temporal lobe concerned with hearing. [NIH] Autoantibodies: Antibodies that react with self-antigens (autoantigens) of the organism that produced them. [NIH] Autoantigens: Endogenous tissue constituents that have the ability to interact with autoantibodies and cause an immune response. [NIH] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by autoimmune diseases. [NIH] Autonomic: 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. Autonomic activity is controlled and integrated by the central nervous system, especially the hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [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] Bactericidal: Substance lethal to bacteria; substance capable of killing 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] 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] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [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
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composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Binaural: Used of the two ears functioning together. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] 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] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biological therapy: Treatment to stimulate or restore the ability of the immune system to fight infection and disease. Also used to lessen side effects that may be caused by some cancer treatments. Also known as immunotherapy, biotherapy, or biological response modifier (BRM) therapy. [NIH] Bioluminescence: The emission of light by living organisms such as the firefly, certain mollusks, beetles, fish, bacteria, fungi and protozoa. [NIH] Biomarkers: Substances sometimes found in an increased amount in the blood, other body fluids, or tissues and that may suggest the presence of some types of cancer. Biomarkers include CA 125 (ovarian cancer), CA 15-3 (breast cancer), CEA (ovarian, lung, breast, pancreas, and GI tract cancers), and PSA (prostate cancer). Also called tumor markers. [NIH] Biometry: The use of statistical methods to analyze biological observations and phenomena. [NIH]
Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Birth Injuries: Mechanical or anoxic trauma incurred by the infant during labor or delivery. [NIH]
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Bladder: The organ that stores urine. [NIH] Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]
Body Fluids: Liquid components of living organisms. [NIH] Bone Conduction: Sound transmission through the bones of the skull to the inner ear. [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 Cells: Cells contained in the bone marrow including fat cells, stromal cells, megakaryocytes, and the immediate precursors of most blood cells. [NIH] Bone Marrow Transplantation: The transference of bone marrow from one human or animal to another. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [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] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [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] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH]
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Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breeding: The science or art of changing the constitution of a population of plants or animals through sexual reproduction. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchial: Pertaining to one or more bronchi. [EU] Brown Fat: A thermogenic form of adipose tissue found in newborns of many species, including humans, and in hibernating mammals. The tissue is capable of rapid liberation of energy and seems to be important in the maintenance of body temperature immediately after birth and upon waking from hibernation. [NIH] Bruxism: A disorder characterized by grinding and clenching of the teeth. [NIH] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Calcification: Deposits of calcium in the tissues of the breast. Calcification in the breast can be seen on a mammogram, but cannot be detected by touch. There are two types of breast calcification, macrocalcification and microcalcification. Macrocalcifications are large deposits and are usually not related to cancer. Microcalcifications are specks of calcium that may be found in an area of rapidly dividing cells. Many microcalcifications clustered together may be a sign of cancer. [NIH] Calcineurin: A calcium- and calmodulin-binding protein present in highest concentrations in the central nervous system. Calcineurin is composed of two subunits. A catalytic subunit, calcineurin A, and a regulatory subunit, calcineurin B, with molecular weights of about 60 kD and 19 kD, respectively. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including histones, myosin light chain, and the regulatory subunit of cAMP-dependent protein kinase. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes in T-lymphocytes that act by inhibiting T-cell activation. EC 3.1.3.-. [NIH] Calcinosis: Pathologic deposition of calcium salts in tissues. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Callus: A callosity or hard, thick skin; the bone-like reparative substance that is formed round the edges and fragments of broken bone. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [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]
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Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiogenic: Originating in the heart; caused by abnormal function of the heart. [EU] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Caspase: Enzyme released by the cell at a crucial stage in apoptosis in order to shred all cellular proteins. [NIH] Catalase: An oxidoreductase that catalyzes the conversion of hydrogen peroxide to water and oxygen. It is present in many animal cells. A deficiency of this enzyme results in acatalasia. EC 1.11.1.6. [NIH] Cataracts: In medicine, an opacity of the crystalline lens of the eye obstructing partially or totally its transmission of light. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] Celiac Disease: A disease characterized by intestinal malabsorption and precipitated by
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gluten-containing foods. The intestinal mucosa shows loss of villous structure. [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 Aggregation: The phenomenon by which dissociated cells intermixed in vitro tend to group themselves with cells of their own type. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell 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] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Centromere: The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. [NIH] Centrosome: The cell center, consisting of a pair of centrioles surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (mitotic spindle apparatus). [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH]
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Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Hemorrhage: Bleeding into a cerebral hemisphere of the brain, including lobar, subcortical white matter, and basal ganglia hemorrhages. Commonly associated conditions include hypertension; intracranial arteriosclerosis; intracranial aneurysm; craniocerebral trauma; intracranial arteriovenous malformations; cerebral amyloid angiopathy; and cerebral infarction. [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]
Cerebral Palsy: Refers to a motor disability caused by a brain dysfunction. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Chaining: Learning of a series of responses in which the stimulus arising from one response is associated with the next response in the series. [NIH] Chaperonins: A class of sequence-related molecular chaperones found in bacteria, mitochondria, and plastids. Chaperonins are abundant constitutive proteins that increase in amount after stresses such as heat shock, bacterial infection of macrophages, and an increase in the cellular content of unfolded proteins. Bacterial chaperonins are major immunogens in human bacterial infections because of their accumulation during the stress of infection. Two members of this class of chaperones are chaperonin 10 and chaperonin 60. [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] 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] Chemotaxis: The movement of cells or organisms toward or away from a substance in response to its concentration gradient. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Child Care: Care of children in the home or institution. [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,
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and in lipid metabolism. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinesterase Inhibitors: Drugs that inhibit cholinesterases. The neurotransmitter acetylcholine is rapidly hydrolyzed, and thereby inactivated, by cholinesterases. When cholinesterases are inhibited, the action of endogenously released acetylcholine at cholinergic synapses is potentiated. Cholinesterase inhibitors are widely used clinically for their potentiation of cholinergic inputs to the gastrointestinal tract and urinary bladder, the eye, and skeletal muscles; they are also used for their effects on the heart and the central nervous system. [NIH] Chorion: The outermost extraembryonic membrane. [NIH] Chorionic Villi: The threadlike, vascular projections of the chorion which enter into the formation of the placenta. [NIH] Choroid: The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. [NIH] Chromaffin System: The cells of the body which stain with chromium salts. They occur along the sympathetic nerves, in the adrenal gland, and in various other organs. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosomal: Pertaining to chromosomes. [EU] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chromosome Abnormalities: Defects in the structure or number of chromosomes resulting in structural aberrations or manifesting as disease. [NIH] Chromosome Segregation: The orderly segregation of chromosomes during meiosis or mitosis. [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] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] 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] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clamp: A u-shaped steel rod used with a pin or wire for skeletal traction in the treatment of certain fractures. [NIH]
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Clathrin: The main structural coat protein of coated vesicles which play a key role in the intracellular transport between membranous organelles. Clathrin also interacts with cytoskeletal proteins. [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] Cleft Palate: Congenital fissure of the soft and/or hard palate, due to faulty fusion. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]
Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] 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] Cluster Analysis: A set of statistical methods used to group variables or observations into strongly inter-related subgroups. In epidemiology, it may be used to analyze a closely grouped series of events or cases of disease or other health-related phenomenon with welldefined distribution patterns in relation to time or place or both. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coated Vesicles: Vesicles formed when cell-membrane coated pits invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as clathrin, coat protein complex proteins, or caveolins. [NIH] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]
Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Cochlear Implants: Electronic devices implanted beneath the skin with electrodes to the cochlear nerve to create sound sensation in persons with sensorineural deafness. [NIH] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [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]
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Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [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. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Coloboma: Congenital anomaly in which some of the structures of the eye are absent due to incomplete fusion of the fetal intraocular fissure during gestation. [NIH] Combination chemotherapy: Treatment using more than one anticancer drug. [NIH] Combinatorial: A cut-and-paste process that churns out thousands of potentially valuable compounds at once. [NIH] Communication Disorders: Disorders of verbal and nonverbal communication caused by receptive or expressive language disorders, cognitive dysfunction (e.g., mental retardation), psychiatric conditions, and hearing disorders. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the
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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] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] 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] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate the "true" effect of an intervention. [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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] 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
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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] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Consumption: Pulmonary tuberculosis. [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]
Contraceptive: An agent that diminishes the likelihood of or prevents conception. [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] Contrast Sensitivity: The ability to detect sharp boundaries (stimuli) and to detect slight changes in luminance at regions without distinct contours. Psychophysical measurements of this visual function are used to evaluate visual acuity and to detect eye disease. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cordocentesis: The collecting of fetal blood samples via ultrasound-guided needle aspiration of the blood in the umbilical vein. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [NIH] Corneal Transplantation: Partial or total replacement of the cornea from one human or animal to another. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD
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results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Cortices: The outer layer of an organ; used especially of the cerebrum and cerebellum. [NIH] 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; 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] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Craniofacial Abnormalities: Congenital structural deformities, malformations, or other abnormalities of the cranium and facial bones. [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] Cribriform: Pierced with small holes as in a sieve. Refers to the appearance of a tumor when viewed under a microscope. The tumor appears to have open spaces or small holes inside. [NIH]
Cricoid Cartilage: The small thick cartilage that forms the lower and posterior parts of the laryngeal wall. [NIH] Criterion: A standard by which something may be judged. [EU] Crossing-over: The exchange of corresponding segments between chromatids of homologous chromosomes during meiosia, forming a chiasma. [NIH] Crowns: A prosthetic restoration that reproduces the entire surface anatomy of the visible
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natural crown of a tooth. It may be partial (covering three or more surfaces of a tooth) or complete (covering all surfaces). It is made of gold or other metal, porcelain, or resin. [NIH] Cues: Signals for an action; that specific portion of a perceptual field or pattern of stimuli to which a subject has learned to respond. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanosis: A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cysteine: A thiol-containing non-essential amino acid that is oxidized to form cystine. [NIH] Cystine: A covalently linked dimeric nonessential amino acid formed by the oxidation of cysteine. Two molecules of cysteine are joined together by a disulfide bridge to form cystine. [NIH]
Cytogenetics: A branch of genetics which deals with the cytological and molecular behavior of genes and chromosomes during cell division. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytosine: A pyrimidine base that is a fundamental unit of nucleic acids. [NIH] Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm. [NIH] 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] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Daunorubicin: Very toxic anthracycline aminoglycoside antibiotic isolated from Streptomyces peucetius and others, used in treatment of leukemias and other neoplasms. [NIH]
De novo: In cancer, the first occurrence of cancer in the body. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decidua: The epithelial lining of the endometrium that is formed before the fertilized ovum reaches the uterus. The fertilized ovum embeds in the decidua. If the ovum is not fertilized, the decidua is shed during menstruation. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deinstitutionalization: The practice of caring for individuals in the community, rather than
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in an institutional environment with resultant effects on the individual, the individual's family, the community, and the health care system. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] 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] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Care: The total of dental diagnostic, preventive, and restorative services provided to meet the needs of a patient (from Illustrated Dictionary of Dentistry, 1982). [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]
Dental implant: A small metal pin placed inside the jawbone to mimic the root of a tooth. Dental implants can be used to help anchor a false tooth or teeth, or a crown or bridge. [NIH] Dental Staff: Personnel who provide dental service to patients in an organized facility, institution or agency. [NIH] Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Dentition: The teeth in the dental arch; ordinarily used to designate the natural teeth in position in their alveoli. [EU] Deoxyribonucleic: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Deoxyribonucleic acid: A polymer of subunits called deoxyribonucleotides which is the primary genetic material of a cell, the material equivalent to genetic information. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Dermatitis: Any inflammation of the skin. [NIH] 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
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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] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diagnostic Services: Organized services for the purpose of providing diagnosis to promote and maintain health. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] 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] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [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] Discriminant Analysis: A statistical analytic technique used with discrete dependent variables, concerned with separating sets of observed values and allocating new values. It is sometimes used instead of regression analysis. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] 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 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
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consciousness and, thus separated, function as a unitary whole. [EU] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Donepezil: A drug used in the treatment of Alzheimer's disease. It belongs to the family of drugs called cholinesterase inhibitors. It is being studied as a treatment for side effects caused by radiation therapy to the brain. [NIH] 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] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Down syndrome: A disorder caused by the presence of an extra chromosome 21 and characterized by mental retardation and distinguishing physical features. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dynein: A transport protein that normally binds proteins to the microtubule. [NIH] Dysplasia: Cells that look abnormal under a microscope but are not cancer. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Eclampsia: Onset of convulsions or coma in a previously diagnosed pre-eclamptic patient. [NIH]
Ectoderm: The outer of the three germ layers of the embryo. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Effusion: The escape of fluid into a part or tissue, as an exudation or a transudation. [EU]
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Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalocele: Cerebral tissue herniation through a congenital or acquired defect in the skull. The majority of congenital encephaloceles occur in the occipital or frontal regions. Clinical features include a protuberant mass that may be pulsatile. The quantity and location of protruding neural tissue determines the type and degree of neurologic deficit. Visual defects, psychomotor developmental delay, and persistent motor deficits frequently occur. [NIH]
Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine Glands: Ductless glands that secrete substances which are released directly into the circulation and which influence metabolism and other body functions. [NIH] Endocrine System: The system of glands that release their secretions (hormones) directly
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into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. Endosomes play a central role in endocytosis. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]
Endometrium: The layer of tissue that lines the uterus. [NIH] Endosomes: Cytoplasmic vesicles formed when coated vesicles shed their clathrin coat. Endosomes internalize macromolecules bound by receptors on the cell surface. [NIH] Endostatin: A drug that is being studied for its ability to prevent the growth of new blood vessels into a solid tumor. Endostatin belongs to the family of drugs called angiogenesis inhibitors. [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 balance: Energy is the capacity of a body or a physical system for doing work. Energy balance is the state in which the total energy intake equals total energy needs. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord.
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An epidural injection is given into this space. [NIH] Epigastric: Having to do with the upper middle area of the abdomen. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithelial: Refers to the cells that line the internal and external surfaces of the body. [NIH] Epithelial Cells: Cells that line the inner and outer surfaces of the body. [NIH] Epithelium: One or more layers of epithelial cells, supported by the basal lamina, which covers the inner or outer surfaces of the body. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophageal Atresia: Congenital failure of the full esophageal lumen to develop that commonly occurs with tracheoesophageal fistula. Symptoms include excessive salivation, gagging, cyanosis, and dyspnea. [NIH] Esophageal Fistula: Abnormal passage communicating with the esophagus. [NIH] Esophageal Motility Disorders: Disorders affecting the motor function of the upper or lower esophageal sphincters, the esophageal body, or a combination of these parts. The failure of the sphincters to maintain a tonic pressure may result in the impeding of the passage of food, regurgitation of food, or reflux of gastric acid into the esophagus. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esotropia: A form of ocular misalignment characterized by an excessive convergence of the visual axes, resulting in a "cross-eye" appearance. An example of this condition occurs when paralysis of the lateral rectus muscle causes an abnormal inward deviation of one eye on attempted gaze. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estriol: (16 alpha,17 beta)-Estra-1,3,5(10)-triene-3,16,17-triol. A metabolite of estradiol and usually the predominant estrogenic metabolite in urine. During pregnancy, large amounts of estriol are produced by the placenta. It has also been obtained from plant sources. The 16 beta-isomer has also been isolated from the urine of pregnant women. [NIH] Estrogen: One of the two female sex hormones. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH]
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Ethmoid: An unpaired cranial bone which helps form the medial walls of the orbits and contains the themoidal air cells which drain into the nose. [NIH] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Eustachian tube: The middle ear cavity is in communication with the back of the nose through the Eustachian tube, which is normally closed, but opens on swallowing, in order to maintain equal air pressure. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exon: The part of the DNA that encodes the information for the actual amino acid sequence of the protein. In many eucaryotic genes, the coding sequences consist of a series of exons alternating with intron sequences. [NIH] Exotropia: A form of ocular misalignment where the visual axes diverge inappropriately. For example, medial rectus muscle weakness may produce this condition as the affected eye will deviate laterally upon attempted forward gaze. An exotropia occurs due to the relatively unopposed force exerted on the eye by the lateral rectus muscle, which pulls the eye in an outward direction. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., collagen, elastin, fibronectins and laminin). [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Eye Abnormalities: Congenital absence of or defects in structures of the eye; may also be hereditary. [NIH] Facial: Of or pertaining to the face. [EU] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root.
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Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Fat: Total lipids including phospholipids. [NIH] Fathers: Male parents, human or animal. [NIH] Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the placenta. The cord blood is blood contained in the umbilical vessels at the time of delivery. [NIH] Fetal Development: Morphologic and physiologic growth and development of the mammalian embryo or fetus. [NIH] Fetoprotein: Transabdominal aspiration of fluid from the amniotic sac with a view to detecting increases of alpha-fetoprotein in maternal blood during pregnancy, as this is an important indicator of open neural tube defects in the fetus. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [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] Fibronectin: An adhesive glycoprotein. One form circulates in plasma, acting as an opsonin; another is a cell-surface protein which mediates cellular adhesive interactions. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fibula: The bone of the lower leg lateral to and smaller than the tibia. In proportion to its length, it is the most slender of the long bones. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral
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cortex which involves the entire thickness of the brain wall. [EU] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flavodoxin: A low-molecular-weight (16,000) iron-free flavoprotein containing one molecule of flavin mononucleotide (FMN) and isolated from bacteria grown on an irondeficient medium. It can replace ferredoxin in all the electron-transfer functions in which the latter is known to serve in bacterial cells. [NIH] 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] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic Acid: N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-Lglutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Follicles: Shafts through which hair grows. [NIH] Fossa: A cavity, depression, or pit. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fucose: Deoxysugar. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]
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] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglion: 1. A knot, or knotlike mass. 2. A general term for a group of nerve cell bodies located outside the central nervous system; occasionally applied to certain nuclear groups within the brain or spinal cord, e.g. basal ganglia. 3. A benign cystic tumour occurring on a
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aponeurosis or tendon, as in the wrist or dorsum of the foot; it consists of a thin fibrous capsule enclosing a clear mucinous fluid. [EU] Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Gene Dosage: The number of copies of a given gene present in a cell or nucleus. An increase in gene dosage can result in the formation of higher levels of gene product, provided that the gene is not subject to autogenous regulation. [NIH] Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] General practitioner: A medical practitioner who does not specialize in a particular branch of medicine or limit his practice to a specific class of diseases. [NIH] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH]
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Genetic Techniques: Chromosomal, biochemical, intracellular, and other methods used in the study of genetics. [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] Genetic transcription: The process by which the genetic information encoded in the gene, represented as a linear sequence of deoxyribonucleotides, is copied into an exactly complementary sequence of ribonucleotides known as messenger RNA. [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] Germ cell tumors: Tumors that begin in the cells that give rise to sperm or eggs. They can occur virtually anywhere in the body and can be either benign or malignant. [NIH] Germ Cells: The reproductive cells in multicellular organisms. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Gestational: Psychosis attributable to or occurring during pregnancy. [NIH] Gestational Age: Age of the conceptus. In humans, this may be assessed by medical history, physical examination, early immunologic pregnancy tests, radiography, ultrasonography, and amniotic fluid analysis. [NIH] Gestures: Movement of a part of the body for the purpose of communication. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomeruli: Plural of glomerulus. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after
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ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]
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]
Gluten: The protein of wheat and other grains which gives to the dough its tough elastic character. [EU] 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] Glycols: A generic grouping for dihydric alcohols with the hydroxy groups (-OH) located on different carbon atoms. They are viscous liquids with high boiling points for their molecular weights. [NIH] Glycolysis: The pathway by which glucose is catabolized into two molecules of pyruvic acid with the generation of ATP. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Glycosaminoglycans: Heteropolysaccharides which contain an N-acetylated hexosamine in a characteristic repeating disaccharide unit. The repeating structure of each disaccharide involves alternate 1,4- and 1,3-linkages consisting of either N-acetylglucosamine or Nacetylgalactosamine. [NIH] Glycosidic: Formed by elimination of water between the anomeric hydroxyl of one sugar and a hydroxyl of another sugar molecule. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Gonadotropic: Stimulating the gonads; applied to hormones of the anterior pituitary which influence the gonads. [EU] Gonadotropin: The water-soluble follicle stimulating substance, by some believed to originate in chorionic tissue, obtained from the serum of pregnant mares. It is used to supplement the action of estrogens. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH]
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Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Granulomas: Small lumps in tissues caused by inflammation. [NIH] Granulosa Cells: Cells of the membrana granulosa lining the vesicular ovarian follicle which become luteal cells after ovulation. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Group Homes: Housing for groups of patients, children, or others who need or desire emotional or physical support. They are usually established as planned, single housekeeping units in residential dwellings that provide care and supervision for small groups of residents, who, although unrelated, live together as a family. [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] Happiness: Highly pleasant emotion characterized by outward manifestations of gratification; joy. [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] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Hearing Disorders: Conditions that impair the transmission or perception of auditory impulses and information from the level of the ear to the temporal cortices, including the sensorineural pathways. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartbeat: One complete contraction of the heart. [NIH] Heat-Shock Proteins: Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. [NIH] Heat-Shock Proteins 90: A class of molecular chaperones whose members act in the mechanism of signal transduction by steroid receptors. [NIH] Helix-loop-helix: Regulatory protein of cell cycle. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by
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centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [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] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis A: Hepatitis caused by hepatovirus. It can be transmitted through fecal contamination of food or water. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatovirus: A genus of Picornaviridae causing infectious hepatitis naturally in humans and experimentally in other primates. It is transmitted through fecal contamination of food or water. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]
Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] 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]
Heterotropia: One in which the angle of squint remains relatively unaltered on conjugate movement of the eyes. [NIH] Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hibernation: The dormant state in which some animal species pass the winter. It is
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characterized by narcosis and by sharp reduction in body temperature and metabolic activity and by a depression of vital signs. It is a natural physiological process in many warm-blooded animals. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Histology: The study of tissues and cells under a microscope. [NIH] Holidays: Days commemorating events. Holidays also include vacation periods. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [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] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hormone therapy: Treatment of cancer by removing, blocking, or adding hormones. Also called endocrine therapy. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Housekeeping: The care and management of property. [NIH] Human Development: Continuous sequential changes which occur in the physiological and psychological functions during the individual's life. [NIH] Humoral: Of, relating to, proceeding from, or involving a bodily humour - now often used of endocrine factors as opposed to neural or somatic. [EU] Humour: 1. A normal functioning fluid or semifluid of the body (as the blood, lymph or bile) especially of vertebrates. 2. A secretion that is itself an excitant of activity (as certain hormones). [EU] 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] Hybridoma: A hybrid cell resulting from the fusion of a specific antibody-producing spleen cell with a myeloma cell. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H,
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atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxides: Inorganic compounds that contain the OH- group. [NIH] Hydroxyl Radical: The univalent radical OH that is present in hydroxides, alcohols, phenols, glycols. [NIH] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperammonemia: Metabolic disorder characterized by elevated level of ammonia in blood. [NIH] Hypercalciuria: Abnormally large amounts of calcium in the urine. [NIH] Hyperemesis: Excessive vomiting. [EU] Hyperphagia: Ingestion of a greater than optimal quantity of food. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertonia: Or hypertony n, pl. hypertonias or hypertonies : hypertonicity. n. Pathology: increased rigidity, tension and spasticity of the muscles. [EU] Hypertrophic cardiomyopathy: Heart muscle disease that leads to thickening of the heart walls, interfering with the heart's ability to fill with and pump blood. [NIH] Hypoplasia: Incomplete development or underdevelopment of an organ or tissue. [EU] Hypoplastic Left Heart Syndrome: A condition characterized by underdevelopment of the left cardiac chambers, atresia or stenosis of the aorta or mitral valve or both, and hypoplasia of the aorta. These anomalies are a common cause of heart failure in early infancy. [NIH] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypothyroidism: Deficiency of thyroid activity. In adults, it is most common in women and is characterized by decrease in basal metabolic rate, tiredness and lethargy, sensitivity to cold, and menstrual disturbances. If untreated, it progresses to full-blown myxoedema. In infants, severe hypothyroidism leads to cretinism. In juveniles, the manifestations are intermediate, with less severe mental and developmental retardation and only mild symptoms of the adult form. When due to pituitary deficiency of thyrotropin secretion it is called secondary hypothyroidism. [EU] Hypotonia: A condition of diminished tone of the skeletal muscles; diminished resistance of muscles to passive stretching. [EU] Id: The part of the personality structure which harbors the unconscious instinctive desires
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and strivings of the individual. [NIH] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune Sera: Serum that contains antibodies. It is obtained from an animal that has been immunized either by antigen injection or infection with microorganisms containing the antigen. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunoglobulin: A protein that acts as an antibody. [NIH] Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunophilin: A drug for the treatment of Parkinson's disease. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Impaction: The trapping of an object in a body passage. Examples are stones in the bile duct or hardened stool in the colon. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Imperforate Anus: A birth defect in which the anal canal fails to develop. The condition is treated with an operation. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH]
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Incision: A cut made in the body during surgery. [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [EU] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] 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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Individuation: A process of differentiation having for its goal the development of the individual personality. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infant Mortality: Perinatal, neonatal, and infant deaths in a given population. [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 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]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [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] Inhibin: Glyceroprotein hormone produced in the seminiferous tubules by the Sertoli cells in the male and by the granulosa cells in the female follicles. The hormone inhibits FSH and LH synthesis and secretion by the pituitary cells thereby affecting sexual maturation and fertility. [NIH] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [NIH] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin
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although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inositol 1,4,5-Trisphosphate: Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4,5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1,4,5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell's endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [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] Institutionalization: The caring for individuals in institutions and their adaptation to routines characteristic of the institutional environment, and/or their loss of adaptation to life outside the institution. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interphase: The interval between two successive cell divisions during which the chromosomes are not individually distinguishable and DNA replication occurs. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intracranial Aneurysm: A saclike dilatation of the walls of a blood vessel, usually an artery. [NIH]
Intracranial Arteriosclerosis: Vascular diseases characterized by thickening, hardening, and remodeling of the walls of intracranial arteries. There are three subtypes: (1) atherosclerosis, marked by fatty depositions in the innermost layer of the arterial walls, (2) Monckeberg's
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sclerosis, which features calcium deposition in the media and (3) arteriolosclerosis, which refers to sclerosis of small caliber arteries. Clinically, this process may be associated with transient ischemic attack, brain infarction, intracranial embolism and thrombosis, or intracranial aneurysm. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intraocular: Within the eye. [EU] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]
Invertebrates: Animals that have no spinal column. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Karyotype: The characteristic chromosome complement of an individual, race, or species as defined by their number, size, shape, etc. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratoconus: A disorder characterized by an irregular corneal surface (cone-shaped) resulting in blurred and distorted images. [NIH]
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Keratolytic: An agent that promotes keratolysis. [EU] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle. [NIH] Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool. [NIH]
Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [NIH] Lag: The time elapsing between application of a stimulus and the resulting reaction. [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] Language Development Disorders: Conditions characterized by language abilities (comprehension and expression of speech and writing) that are below the expected level for a given age, generally in the absence of an intellectual impairment. These conditions may be associated with deafness; brain diseases; mental disorders; or environmental factors. [NIH] Language Disorders: Conditions characterized by deficiencies of comprehension or expression of written and spoken forms of language. These include acquired and developmental disorders. [NIH] Language Therapy: Rehabilitation of persons with language disorders or training of children with language development disorders. [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] Laryngectomy: Total or partial excision of the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH] Lectin: A complex molecule that has both protein and sugars. Lectins are able to bind to the outside of a cell and cause biochemical changes in it. Lectins are made by both animals and plants. [NIH] Lemur: A genus of the family Lemuridae consisting of five species: L. catta (ring-tailed lemur), L. fulvus, L. macaco (acoumba or black lemur), L. mongoz (mongoose lemur), and L. variegatus (white lemur). Most members of this genus occur in forested areas on
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Madagascar and the Comoro Islands. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leptin: A 16-kD peptide hormone secreted from white adipocytes and implicated in the regulation of food intake and energy balance. Leptin provides the key afferent signal from fat cells in the feedback system that controls body fat stores. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leucocyte: All the white cells of the blood and their precursors (myeloid cell series, lymphoid cell series) but commonly used to indicate granulocytes exclusive of lymphocytes. [NIH]
Leukaemia: An acute or chronic disease of unknown cause in man and other warm-blooded animals that involves the blood-forming organs, is characterized by an abnormal increase in the number of leucocytes in the tissues of the body with or without a corresponding increase of those in the circulating blood, and is classified according of the type leucocyte most prominently involved. [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] Leukoencephalopathy: A condition with spongy holes in the brain's white matter. [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] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Linkage Disequilibrium: Nonrandom association of linked genes. This is the tendency of the alleles of two separate but already linked loci to be found together more frequently than would be expected by chance alone. [NIH] Lip: Either of the two fleshy, full-blooded margins of the mouth. [NIH] Lipid: Fat. [NIH]
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Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipopolysaccharide: Substance consisting of polysaccaride and lipid. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver cancer: A disease in which malignant (cancer) cells are found in the tissues of the liver. [NIH]
Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [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] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] 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] Long-Term Potentiation: A persistent increase in synaptic efficacy, usually induced by appropriate activation of the same synapses. The phenomenological properties of long-term potentiation suggest that it may be a cellular mechanism of learning and memory. [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] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [NIH]
Lumen: The cavity or channel within a tube or tubular organ. [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 matter, invertebrates and other living organisms. For the luminescence of bacteria, bacterial luminescence is available. [NIH] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [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] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of
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connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]
Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphatic system: The tissues and organs that produce, store, and carry white blood cells that fight infection and other diseases. This system includes the bone marrow, spleen, thymus, lymph nodes and a network of thin tubes that carry lymph and white blood cells. These tubes branch, like blood vessels, into all the tissues of the body. [NIH] Lymphoblastic: One of the most aggressive types of non-Hodgkin lymphoma. [NIH] Lymphoblasts: Interferon produced predominantly by leucocyte cells. [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] Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue. [NIH] Lysosomal Storage Diseases: Inborn errors of metabolism characterized by defects in specific lysosomal hydrolases and resulting in intracellular accumulation of unmetabolized substrates. [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] Malabsorption: Impaired intestinal absorption of nutrients. [EU] Malabsorption syndrome: A group of symptoms such as gas, bloating, abdominal pain, and diarrhea resulting from the body's inability to properly absorb nutrients. [NIH] Malformation: A morphologic developmental process. [EU]
defect
resulting
from
an
intrinsically
abnormal
Malignancy: A cancerous tumor that can invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Malondialdehyde: The dialdehyde of malonic acid. [NIH] Mammogram: An x-ray of the breast. [NIH] Mandible: The largest and strongest bone of the face constituting the lower jaw. It supports the lower teeth. [NIH] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Matrix metalloproteinase: A member of a group of enzymes that can break down proteins, such as collagen, that are normally found in the spaces between cells in tissues (i.e.,
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extracellular matrix proteins). Because these enzymes need zinc or calcium atoms to work properly, they are called metalloproteinases. Matrix metalloproteinases are involved in wound healing, angiogenesis, and tumor cell metastasis. [NIH] Maxillary: Pertaining to the maxilla : the irregularly shaped bone that with its fellow forms the upper jaw. [EU] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediastinal Cyst: Cysts of one of the parts of the mediastinum: the superior part, containing the trachea, esophagus, thoracic duct and thymus organs; the inferior middle part, containing the pericardium; the inferior anterior part containing some lymph nodes; and the inferior posterior part, containing the thoracic duct and esophagus. [NIH] Mediastinum: The area between the lungs. The organs in this area include the heart and its large blood vessels, the trachea, the esophagus, the bronchi, and lymph nodes. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megacolon: Pathological enlargement of the colon. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Fusion: The adherence of cell membranes, intracellular membranes, or artifical membrane models of either to each other or to viruses, parasites, or interstitial particles through a variety of chemical and physical processes. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [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] Menarche: The establishment or beginning of the menstrual function. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstrual Cycle: The period of the regularly recurring physiologic changes in the endometrium occurring during the reproductive period in human females and some primates and culminating in partial sloughing of the endometrium (menstruation). [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH]
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Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]
Mesoderm: The middle germ layer of the embryo. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metaphase: The second phase of cell division, in which the chromosomes line up across the equatorial plane of the spindle prior to separation. [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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] Microcalcifications: Tiny deposits of calcium in the breast that cannot be felt but can be detected on a mammogram. A cluster of these very small specks of calcium may indicate that cancer is present. [NIH] Micromanipulation: The performance of dissections, injections, surgery, etc., by the use of micromanipulators (attachments to a microscope that manipulate tiny instruments). [NIH] Micromanipulators: A high precision instrument used in microinjection or chromosome dissection activities. [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] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microscopy: The application of microscope magnification to the study of materials that cannot be properly seen by the unaided eye. [NIH]
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Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mime: Facial expression. (NOT: mimicry = adaptation for survival in which an organism takes on the semblance another organism or a non-living object.) [EU] Mineralization: The action of mineralizing; the state of being mineralized. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mitotic: Cell resulting from mitosis. [NIH] Mitotic inhibitors: Drugs that kill cancer cells by interfering with cell division (mitostis). [NIH]
Mitotic Spindle Apparatus: An organelle consisting of three components: (1) the astral microtubules, which form around each centrosome and extend to the periphery; (2) the polar microtubules which extend from one spindle pole to the equator; and (3) the kinetochore microtubules, which connect the centromeres of the various chromosomes to either centrosome. [NIH] Mitral Valve: The valve between the left atrium and left ventricle of the heart. [NIH] Mitral Valve Prolapse: Abnormal protrusion of one or both of the leaflets of the mitral valve into the left atrium during systole. This may be accompanied by mitral regurgitation, systolic murmur, nonejection click, or cardiac arrhythmia. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Modulator: A specific inductor that brings out characteristics peculiar to a definite region. [EU]
Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Chaperones: A family of cellular proteins that mediate the correct assembly or disassembly of other polypeptides, and in some cases their assembly into oligomeric structures, but which are not components of those final structures. It is believed that chaperone proteins assist polypeptides to self-assemble by inhibiting alternative assembly pathways that produce nonfunctional structures. Some classes of molecular chaperones are the nucleoplasmins, the chaperonins, the heat-shock proteins 70, and the heat-shock proteins 90. [NIH] 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,
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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] Mononuclear: A cell with one nucleus. [NIH] Monosomy: The condition in which one chromosome of a pair is missing. In a normally diploid cell it is represented symbolically as 2N-1. [NIH] 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] Mosaicism: The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from a single zygote, as opposed to chimerism in which the different cell populations are derived from more than one zygote. [NIH] Motility: The ability to move spontaneously. [EU] Motor Skills: Performance of complex motor acts. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucociliary: Pertaining to or affecting the mucus membrane and hairs (including eyelashes, nose hair, .): mucociliary clearing: the clearance of mucus by ciliary movement ( particularly in the respiratory system). [EU] Mucopolysaccharidoses: Group of lysosomal storage diseases each caused by an inherited deficiency of an enzyme involved in the degradation of glycosaminoglycans (mucopolysaccharides). The diseases are progressive and often display a wide spectrum of clinical severity within one enzyme deficiency. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [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] Multivalent: Pertaining to a group of 5 or more homologous or partly homologous chromosomes during the zygotene stage of prophase to first metaphasis in meiosis. [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]
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Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] Mustard Gas: Severe irritant and vesicant of skin, eyes, and lungs. It may cause blindness and lethal lung edema and was formerly used as a war gas. The substance has been proposed as a cytostatic and for treatment of psoriasis. It has been listed as a known carcinogen in the Fourth Annual Report on Carcinogens (NTP-85-002, 1985) (Merck, 11th ed). [NIH] Mutagen: Any agent, such as X-rays, gamma rays, mustard gas, TCDD, that can cause abnormal mutation in living cells; having the power to cause mutations. [NIH] Mutagenesis: Process of generating genetic mutations. It may occur spontaneously or be induced by mutagens. [NIH] Mutagenic: Inducing genetic mutation. [EU] Mutism: Inability or refusal to speak. [EU] Myelin: The fatty substance that covers and protects nerves. [NIH] Myelodysplasia: Abnormal bone marrow cells that may lead to myelogenous leukemia. [NIH]
Myelodysplastic syndrome: Disease in which the bone marrow does not function normally. Also called preleukemia or smoldering leukemia. [NIH] Myelogenous: Produced by, or originating in, the bone marrow. [NIH] Myeloma: Cancer that arises in plasma cells, a type of white blood cell. [NIH] Myeloproliferative Disorders: Disorders in which one or more stimuli cause proliferation of hemopoietically active tissue or of tissue which has embryonic hemopoietic potential. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH] Myositis: Inflammation of a voluntary muscle. [EU] Nasal Bone: Either of two small elongated rectangular bones that together form the bridge of the nose. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [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] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH]
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Neonatal: Pertaining to the first four weeks after birth. [EU] Neonatal Screening: The identification of selected parameters in newborn infants by various tests, examinations, or other procedures. Screening may be performed by clinical or laboratory measures. A screening test is designed to sort out healthy neonates from those not well, but the screening test is not intended as a diagnostic device, rather instead as epidemiologic. [NIH] Neoplasm: A new growth of benign or malignant tissue. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] 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] Nerve Growth Factor: Nerve growth factor is the first of a series of neurotrophic factors that were found to influence the growth and differentiation of sympathetic and sensory neurons. It is comprised of alpha, beta, and gamma subunits. The beta subunit is responsible for its growth stimulating activity. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neural Crest: A strip of specialized ectoderm flanking each side of the embryonal neural plate, which after the closure of the neural tube, forms a column of isolated cells along the dorsal aspect of the neural tube. Most of the cranial and all of the spinal sensory ganglion cells arise by differentiation of neural crest cells. [NIH] Neural tube defects: These defects include problems stemming from fetal development of the spinal cord, spine, brain, and skull, and include birth defects such as spina bifida, anencephaly, and encephalocele. Neural tube defects occur early in pregnancy at about 4 to 6 weeks, usually before a woman knows she is pregnant. Many babies with neural tube defects have difficulty walking and with bladder and bowel control. [NIH] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
Neurodegenerative Diseases: Hereditary and sporadic conditions which are characterized by progressive nervous system dysfunction. These disorders are often associated with atrophy of the affected central or peripheral nervous system structures. [NIH] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments: medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain
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classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [NIH] Neurologic: Having to do with nerves or the nervous system. [NIH] Neuroma: A tumor that arises in nerve cells. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neuronal atrophy: Nerve cell death and functional loss. [NIH] 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] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosciences: The scientific disciplines concerned with the embryology, anatomy, physiology, biochemistry, pharmacology, etc., of the nervous sytem. [NIH] Neurosecretory Systems: A system of neurons that has the specialized function to produce and secrete hormones, and that constitutes, in whole or in part, an endocrine organ or system. [NIH] Neurotoxic: Poisonous or destructive to nerve tissue. [EU] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophil: A type of white blood cell. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It
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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] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH] Nucleates: Bacteria-inducing ice nucleation at warm temperatures (between zero and minus ten degrees C.). [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] 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] Nystagmus: Rhythmical oscillation of the eyeballs, either pendular or jerky. [NIH] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [EU] Obsessional: Neurosis characterized by the repetitive intrusion into the mind, against volition, of ideas, numinations and phobias, often associated with compulsive actions. [NIH] Occupational Exposure: The exposure to potentially harmful chemical, physical, or biological agents that occurs as a result of one's occupation. [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]
Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU]
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Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Olfaction: Function of the olfactory apparatus to perceive and discriminate between the molecules that reach it, in gas form from an external environment, directly or indirectly via the nose. [NIH] Olfactory Bulb: Ovoid body resting on the cribriform plate of the ethmoid bone where the olfactory nerve terminates. The olfactory bulb contains several types of nerve cells including the mitral cells, on whose dendrites the olfactory nerve synapses, forming the olfactory glomeruli. The accessory olfactory bulb, which receives the projection from the vomeronasal organ via the vomeronasal nerve, is also included here. [NIH] Olfactory Mucosa: That portion of the nasal mucosa containing the sensory endings for olfaction; the organ of smell. [NIH] Oligosaccharides: Carbohydrates consisting of between two and ten monosaccharides connected by either an alpha- or beta-glycosidic link. They are found throughout nature in both the free and bound form. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [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] Ophthalmic: Pertaining to the eye. [EU] Ophthalmologist: A medical doctor specializing in the diagnosis and medical or surgical treatment of visual disorders and eye disease. [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] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orbit: One of the two cavities in the skull which contains an eyeball. Each eye is located in a bony socket or orbit. [NIH] Orbital: Pertaining to the orbit (= the bony cavity that contains the eyeball). [EU] Orderly: A male hospital attendant. [NIH] Orofacial: Of or relating to the mouth and face. [EU]
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Orthodontics: A dental specialty concerned with the prevention and correction of dental and oral anomalies (malocclusion). [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [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] Osteotomy: The surgical cutting of a bone. [EU] Otitis: Inflammation of the ear, which may be marked by pain, fever, abnormalities of hearing, hearing loss, tinnitus, and vertigo. [EU] Otitis Media: Inflammation of the middle ear. [NIH] Ovarian Follicle: Spheroidal cell aggregation in the ovary containing an ovum. It consists of an external fibro-vascular coat, an internal coat of nucleated cells, and a transparent, albuminous fluid in which the ovum is suspended. [NIH] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Ovulation: The discharge of a secondary oocyte from a ruptured graafian follicle. [NIH] Ovulation Induction: Techniques for the artifical induction of ovulation. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Ovum Implantation: Endometrial implantation of the blastocyst. [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 Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [NIH] Palate: The structure that forms the roof of the mouth. It consists of the anterior hard palate and the posterior soft palate. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Paranasal Sinuses: Air-filled extensions of the respiratory part of the nasal cavity into the frontal, ethmoid, sphenoid, and maxillary cranial bones. They vary in size and form in different individuals and are lined by the ciliated mucous membranes of the nasal cavity. [NIH]
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Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parenchyma: The essential elements of an organ; used in anatomical nomenclature as a general term to designate the functional elements of an organ, as distinguished from its framework, or stroma. [EU] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Parietal Lobe: Upper central part of the cerebral hemisphere. [NIH] Parotid: The space that contains the parotid gland, the facial nerve, the external carotid artery, and the retromandibular vein. [NIH] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Partnership Practice: A voluntary contract between two or more doctors who may or may not share responsibility for the care of patients, with proportional sharing of profits and losses. [NIH] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Paternal Age: Age of the father. [NIH] 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] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Advocacy: Promotion and protection of the rights of patients, frequently through a legal process. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pediatrics: A medical specialty concerned with maintaining health and providing medical care to children from birth to adolescence. [NIH] Pelvic: Pertaining to the pelvis. [EU] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH]
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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] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Pericardium: The fibroserous sac surrounding the heart and the roots of the great vessels. [NIH]
Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peripheral blood: Blood circulating throughout the body. [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] 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] Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. [NIH] Peritoneum: Endothelial lining of the abdominal cavity, the parietal peritoneum covering the inside of the abdominal wall and the visceral peritoneum covering the bowel, the mesentery, and certain of the organs. The portion that covers the bowel becomes the serosal layer of the bowel wall. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phobias: An exaggerated and invariably pathological dread of some specific type of stimulus or situation. [NIH] Phosphodiesterase: Effector enzyme that regulates the levels of a second messenger, the cyclic GMP. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or
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glycerophosphatidates. EC 3.1.-. [NIH] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Physical Examination: Systematic and thorough inspection of the patient for physical signs of disease or abnormality. [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Piracetam: A compound suggested to be both a nootropic and a neuroprotective agent. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Placental Extracts: Extracts prepared from placental tissue; they may contain specific but uncharacterized factors or proteins with specific activities. [NIH] Placental tissue: The tissue intervening between fetal blood and maternal blood in the placenta; it acts as a selective membrane regulating the passage of substances from the maternal to the fetal blood. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Plasma protein: One of the hundreds of different proteins present in blood plasma,
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including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [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 Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelet-Derived Growth Factor: Mitogenic peptide growth hormone carried in the alphagranules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication. [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]
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 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]
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Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] 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-translational: The cleavage of signal sequence that directs the passage of the protein through a cell or organelle membrane. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panel
